Trial Outcomes & Findings for Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout (NCT NCT03994731)

NCT ID: NCT03994731

Last Updated: 2024-06-26

Results Overview

Responders are defined as participants achieving and maintaining sUA \< 6 mg/dL for at least 80% of the time during Month 6. Month 6 includes pre- and post-infusion sUA assessments at Weeks 20 and 22, non-infusion sUA at Weeks 21 and 23, pre-infusion sUA at Week 24 and any unscheduled sUA between Week 20 and Week 24. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA \>6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 152 participants
• Primary outcome timeframe: Month 6 (Weeks 20, 21, 22, 23 and 24)
• Results posted on: 2024-06-26

Participant Flow

This study included a 2-week MTX Tolerability Assessment Period consisting of 2 weeks oral MTX. 159 participants received MTX in this period. The 7 participants who were unable to tolerate MTX in this period or who met other exclusion criteria were not randomized, were classified as screen failures, and were not considered enrolled per protocol section 9.4.6.3.2.2. 152 randomized participants were considered enrolled in this trial.

Participant milestones

Measure	Pegloticase + MTX Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral MTX 15 mg, participants received intravenous (IV) pegloticase 8 mg every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.	Pegloticase + Placebo Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Run-in Period (From Week -4 to Day 1) STARTED	100	52
Run-in Period (From Week -4 to Day 1) Took at Least 1 Dose of MTX or Placebo	98	51
Run-in Period (From Week -4 to Day 1) COMPLETED	96	49
Run-in Period (From Week -4 to Day 1) NOT COMPLETED	4	3
Pegloticase + IMM Period STARTED	96	49
Pegloticase + IMM Period COMPLETED	76	34
Pegloticase + IMM Period NOT COMPLETED	20	15

Reasons for withdrawal

Measure	Pegloticase + MTX Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral MTX 15 mg, participants received intravenous (IV) pegloticase 8 mg every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.	Pegloticase + Placebo Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + IMM Period Death	2	0
Pegloticase + IMM Period Lost to Follow-up	3	6
Pegloticase + IMM Period Withdrawal by Subject	15	9

Baseline Characteristics

Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout

Baseline characteristics by cohort

Measure	Pegloticase + MTX n=100 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=52 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Total n=152 Participants Total of all reporting groups
Age, Continuous	55.6 years STANDARD_DEVIATION 12.74 • n=5 Participants	53.0 years STANDARD_DEVIATION 12.12 • n=7 Participants	54.7 years STANDARD_DEVIATION 12.56 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	44 Participants n=7 Participants	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	9 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=5 Participants	42 Participants n=7 Participants	123 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	69 Participants n=5 Participants	36 Participants n=7 Participants	105 Participants n=5 Participants
Race/Ethnicity, Customized Other, Not Specified	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6 (Weeks 20, 21, 22, 23 and 24)

Population: Intent-to-treat (ITT) Population: all randomized participants.

Responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6. Month 6 includes pre- and post-infusion sUA assessments at Weeks 20 and 22, non-infusion sUA at Weeks 21 and 23, pre-infusion sUA at Week 24 and any unscheduled sUA between Week 20 and Week 24. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.

Outcome measures

Measure	Pegloticase + MTX n=100 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=52 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6	71.0 percentage of participants Interval 61.1 to 79.6	38.5 percentage of participants Interval 25.3 to 53.0

SECONDARY outcome

Timeframe: Month 12 (Weeks 48, 50 and 52)

Population: ITT Population: all randomized participants.

Responders are defined as participants achieving and maintaining sUA <6 mg/dL for at least 80% of the time during Month 12 (Weeks 48, 50 and 52). Month 12 includes pre- and post-infusion sUA Weeks 48 and 50, pre-infusion sUA at Week 52, and any unscheduled sUA assessments done at unscheduled visits between Week 48 and 52. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.

Outcome measures

Measure	Pegloticase + MTX n=100 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=52 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Percentage of sUA (sUA < 6 mg/dL) Responders During Month 12	60.0 percentage of participants Interval 49.7 to 69.7	30.8 percentage of participants Interval 18.7 to 45.1

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT Population: all randomized participants with ≥ 1 tophi at baseline. Modified non-responder imputation was done for participants with missing tophi evaluation data at Week 52.

Percentage of participants with complete resolution of ≥ 1 tophi (using digital photography) at Week 52 in participants with tophi at baseline. Participants with resolution of ≥ 1 tophi at a visit are participants with resolution of ≥ 1 tophi at the visit (i.e. have complete response), and no progressive disease for any other tophi.

Outcome measures

Measure	Pegloticase + MTX n=52 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=29 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Percentage of Participants With Complete Resolution of ≥ 1 Tophi at Week 52	53.8 percentage of participants	31.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT Population: all randomized participants. Participants with an assessment at Week 52.

HAQ-DI is a self-report functional status instrument that is filled out by the participant and measures disability over the past week via 20 questions relating to 8 domains of function: dressing, grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.

Outcome measures

Measure	Pegloticase + MTX n=76 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=34 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Mean Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52	-0.35 score on a scale Standard Error 0.049	-0.31 score on a scale Standard Error 0.071

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT Population: all randomized participants. Participants with an assessment at Week 52.

The HAQ-Pain score rates the participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.

Outcome measures

Measure	Pegloticase + MTX n=76 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=34 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Mean Change From Baseline HAQ Pain Score at Week 52	-31.02 score on a scale Standard Error 2.208	-22.59 score on a scale Standard Error 3.230

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT Population: all randomized participants. Participants with an assessment at Week 52.

The HAQ health scale is a self-reported measure of overall health. Participants are asked to rate how they are doing, considering all the ways arthritis affects them, on a scale of 0 to 100, where 0 represents very well and 100 represents very poor. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.

Outcome measures

Measure	Pegloticase + MTX n=76 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo n=34 Participants Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Mean Change From Baseline in HAQ Health Score at Week 52	-28.85 score on a scale Standard Error 2.531	-18.69 score on a scale Standard Error 3.722

Adverse Events

MTX: Methotrexate Tolerability Assessment Period

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Pegloticase + MTX: Run-In Period

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Pegloticase + Placebo: Run-In Period

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Pegloticase + MTX: Pegloticase + IMM Period

Serious events: 13 serious events

Other events: 71 other events

Deaths: 2 deaths

Pegloticase + Placebo: Pegloticase + IMM Period

Serious events: 5 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Measure	MTX: Methotrexate Tolerability Assessment Period n=159 participants at risk Participants received open-label oral MTX 15 mg for 2 weeks. Participants not tolerating MTX were designated as screen failures).	Pegloticase + MTX: Run-In Period n=98 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo: Run-In Period n=51 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + MTX: Pegloticase + IMM Period n=96 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo: Pegloticase + IMM Period n=49 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Cardiac disorders Cardiac Arrest	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Cardiac disorders Mitral Valve Incompetence	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Endocrine disorders Inappropriate Antidiuretic Hormone Secretion	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
General disorders Non-Cardiac Chest Pain	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Immune system disorders Anaphylactic Reaction	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	4.1% 2/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Infections and infestations Abscess Soft Tissue	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Infections and infestations Covid-19	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.1% 2/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Infections and infestations Osteomyelitis	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Injury, poisoning and procedural complications Facial Bones Fracture	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Injury, poisoning and procedural complications Gun Shot Wound	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Injury, poisoning and procedural complications Infusion Related Reaction	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Investigations Blood Bilirubin Increased	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Metabolism and nutrition disorders Failure To Thrive	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Musculoskeletal and connective tissue disorders Polymyalgia Rheumatica	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Nervous system disorders Subarachnoid Haemorrhage	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Nervous system disorders Syncope	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	2.0% 1/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Renal and urinary disorders Nephrolithiasis	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.

Other adverse events

Measure	MTX: Methotrexate Tolerability Assessment Period n=159 participants at risk Participants received open-label oral MTX 15 mg for 2 weeks. Participants not tolerating MTX were designated as screen failures).	Pegloticase + MTX: Run-In Period n=98 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo: Run-In Period n=51 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + MTX: Pegloticase + IMM Period n=96 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral MTX 15 mg, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.	Pegloticase + Placebo: Pegloticase + IMM Period n=49 participants at risk Participants were randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period. During the Pegloticase + IMM Period, in addition to oral placebo for MTX, participants received IV pegloticase 8 mg Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants were also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Gastrointestinal disorders Nausea	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	5.2% 5/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	12.2% 6/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Gastrointestinal disorders Vomiting	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	8.2% 4/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
General disorders Fatigue	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	5.2% 5/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	4.1% 2/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Infections and infestations COVID-19	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	7.3% 7/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	6.1% 3/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	26.5% 13/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Metabolism and nutrition disorders Gout	28.3% 45/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	28.6% 28/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	19.6% 10/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	66.7% 64/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	71.4% 35/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	13.5% 13/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	10.2% 5/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	5.2% 5/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	4.1% 2/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	6.1% 3/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.
Vascular disorders Hypertension	0.00% 0/159 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/98 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	0.00% 0/51 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	1.0% 1/96 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.	6.1% 3/49 • All Cause Mortality: from signing of informed consent up to Week 52 plus 30 days after last pegloticase infusion (±3 days). Adverse events (AEs)in the Run-in Period: Week -6 up to Day 1 (predose). AEs in the Pegloticase + IMM Period: Day 1 up to Week 52 plus 30 days after last pegloticase infusion (±3 days). The number of participants at risk is not consistent with the Participant Flow data table because the 7 participants who were not randomized after receiving MTX during the 2-week MTX Tolerability Assessment Period were not considered enrolled.

Additional Information

Medical Monitor

Horizon Therapeutics USA, Inc.

Phone: 866-479-6742

Email: clinicaltrials@horizontherapeutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.
• Publication restrictions are in place

Restriction type: OTHER