Trial Outcomes & Findings for A Study With Tocilizumab [RoActemra/Actemra] Monotherapy or in Combination With Methotrexate in Patients With Rheumatoid Arthritis (PICTURE) (NCT NCT01063062)

Last Updated: 2017-08-21

Results Overview

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

107 participants

Primary outcome timeframe

Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24)

Results posted on

2017-08-21

Participant Flow

107 participants were enrolled from 11 centers in Egypt, 2 centers were prematurely terminated.

Patients in this 1 arm tocilizumab study were divided into 2 groups: tocilizumab monotherapy or tocilizumab plus methotrexate (patients taking disease-modifying antirheumatic drugs at Baseline who continued concomitant treatment with methotrexate as per standard of care at the investigator's discretion).

Participant milestones

Participant milestones
Measure	Tocilizumab Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Overall Study STARTED	30	77
Overall Study Received Study Drug	29	76
Overall Study COMPLETED	22	65
Overall Study NOT COMPLETED	8	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Overall Study Patient withdrew consent	0	1
Overall Study Adverse Event	2	4
Overall Study Protocol Violation	5	4
Overall Study Investigator's request	1	0
Overall Study Lost to Follow-up	0	2
Overall Study Miscellaneous reason	0	1

Baseline Characteristics

A Study With Tocilizumab [RoActemra/Actemra] Monotherapy or in Combination With Methotrexate in Patients With Rheumatoid Arthritis (PICTURE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab Monotherapy n=30 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=77 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.	Total n=107 Participants Total of all reporting groups
Age, Continuous	37.78 years STANDARD_DEVIATION 12.47 • n=5 Participants	41.76 years STANDARD_DEVIATION 11.84 • n=7 Participants	40.64 years STANDARD_DEVIATION 12.10 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	69 Participants n=7 Participants	92 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24)

Population: Intent-to-treat (ITT) population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward was applied for missing data.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity Week 4	27.59 percentage of participants	18.42 percentage of participants
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity Week 8	34.48 percentage of participants	40.79 percentage of participants
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity Week 12	34.48 percentage of participants	38.16 percentage of participants
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity Week 16	44.83 percentage of participants	47.37 percentage of participants
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity Week 20	62.07 percentage of participants	57.89 percentage of participants
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity Week 24	58.62 percentage of participants	59.21 percentage of participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: Intent-to-treat population included all participants who received at least one dose of study drug and had data for at least one follow-up variable available. Last observation carried forward.

Time to DAS28 Low Disease Activity was defined as the time in days from the first infusion of study drug to the achievement of a DAS28 Score \<3.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Time to DAS28 Low Disease Activity	107.2 days Interval 84.57 to 129.78	100.2 days Interval 87.49 to 112.93

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24

Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.

DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Percentage of Participants Achieving DAS28 Clinically Significant Improvement Week 4	62.07 percentage of participants	73.68 percentage of participants
Percentage of Participants Achieving DAS28 Clinically Significant Improvement Week 8	75.86 percentage of participants	86.84 percentage of participants
Percentage of Participants Achieving DAS28 Clinically Significant Improvement Week 12	75.86 percentage of participants	90.79 percentage of participants
Percentage of Participants Achieving DAS28 Clinically Significant Improvement Week 16	79.31 percentage of participants	92.11 percentage of participants
Percentage of Participants Achieving DAS28 Clinically Significant Improvement Week 20	82.76 percentage of participants	90.79 percentage of participants
Percentage of Participants Achieving DAS28 Clinically Significant Improvement Week 24	86.20 percentage of participants	96.10 percentage of participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.

Time to DAS28 Clinically Significant Improvement was the Time in days from the first infusion of study drug to the achievement of a DAS28 score reduction of at least 1.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Time to DAS28 Clinically Significant Improvement	59.9 days Interval 40.2 to 79.53	41.6 days Interval 34.51 to 48.76

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24

Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.

DAS28 Remission was defined as a DAS28 score \< 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Percentage of Participants Achieving DAS28 Remission Week 4	17.24 percentage of participants	9.21 percentage of participants
Percentage of Participants Achieving DAS28 Remission Week 8	31.03 percentage of participants	23.68 percentage of participants
Percentage of Participants Achieving DAS28 Remission Week 12	31.03 percentage of participants	27.63 percentage of participants
Percentage of Participants Achieving DAS28 Remission Week 16	34.48 percentage of participants	34.21 percentage of participants
Percentage of Participants Achieving DAS28 Remission Week 20	41.38 percentage of participants	40.79 percentage of participants
Percentage of Participants Achieving DAS28 Remission Week 24	48.28 percentage of participants	40.79 percentage of participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.

Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score \< 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Time to DAS28 Remission	115.9 days Interval 94.24 to 137.49	120.5 days Interval 108.38 to 132.57

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24

Population: Participants from the intent-to-treat population, all participants who received study drug and had at least 1 follow-up variable, with data available at the given time-point. Last observation carried forward.

Outcome measures

Outcome measures
Measure	Tocilizumab n=25 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=75 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Disease Activity Score 28 (DAS28) Week 8	3.72 score on a scale Standard Deviation 1.71	3.68 score on a scale Standard Deviation 1.60
Disease Activity Score 28 (DAS28) Week 12	3.37 score on a scale Standard Deviation 1.62	3.54 score on a scale Standard Deviation 1.45
Disease Activity Score 28 (DAS28) Week 16	3.25 score on a scale Standard Deviation 1.54	3.21 score on a scale Standard Deviation 1.43
Disease Activity Score 28 (DAS28) Week 24	2.51 score on a scale Standard Deviation 1.50	3.06 score on a scale Standard Deviation 1.51
Disease Activity Score 28 (DAS28) Week 20	2.86 score on a scale Standard Deviation 1.50	3.11 score on a scale Standard Deviation 1.44
Disease Activity Score 28 (DAS28) Week 4 (n=24,75)	4.17 score on a scale Standard Deviation 1.45	4.48 score on a scale Standard Deviation 1.47

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24

Population: Participants from the intent-to-treat population, all participants who received study drug and had data for at least one follow-up variable, with data available for the given timepoint.

Blood was collected for C-Reactive Protein (CRP), a test for inflammation, at Weeks 4, 8, 12, 16, 20 and 24 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL).

Outcome measures

Outcome measures
Measure	Tocilizumab n=25 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=75 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
C-Reactive Protein (CRP) Week 4	13.04 mg/L Standard Deviation 24.90	12.28 mg/L Standard Deviation 28.37
C-Reactive Protein (CRP) Week 8 (n=25,74)	14.74 mg/L Standard Deviation 35.74	6.24 mg/L Standard Deviation 13.39
C-Reactive Protein (CRP) Week 12	9.35 mg/L Standard Deviation 17.29	6.89 mg/L Standard Deviation 15.84
C-Reactive Protein (CRP) Week 16	4.38 mg/L Standard Deviation 9.98	3.87 mg/L Standard Deviation 11.01
C-Reactive Protein (CRP) Week 20	7.92 mg/L Standard Deviation 15.07	4.20 mg/L Standard Deviation 12.11
C-Reactive Protein (CRP) Week 24	6.99 mg/L Standard Deviation 13.64	3.82 mg/L Standard Deviation 13.39

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24

Blood was collected for Erythrocyte Sedimentation Rate (ESR), a test to assess inflammation, at Weeks 4, 8, 12, 16, 20, 24 and was analyzed at a central laboratory. ESR was measured in millimeters/hour (mm/hr).

Outcome measures

Outcome measures
Measure	Tocilizumab n=25 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=27 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Erythrocyte Sedimentation Rate (ESR) Week 16	15.80 mm/hr Standard Deviation 23.65	13.88 mm/hr Standard Deviation 18.02
Erythrocyte Sedimentation Rate (ESR) Week 4 (n=24,27)	21.08 mm/hr Standard Deviation 22.27	20.37 mm/hr Standard Deviation 25.66
Erythrocyte Sedimentation Rate (ESR) Week 8	17.18 mm/hr Standard Deviation 21.54	13.79 mm/hr Standard Deviation 18.52
Erythrocyte Sedimentation Rate (ESR) Week 12	14.12 mm/hr Standard Deviation 15.10	16.41 mm/hr Standard Deviation 22.25
Erythrocyte Sedimentation Rate (ESR) Week 20	16.32 mm/hr Standard Deviation 25.44	14.28 mm/hr Standard Deviation 20.42
Erythrocyte Sedimentation Rate (ESR) Week 24	16.32 mm/hr Standard Deviation 22.43	16.40 mm/hr Standard Deviation 22.26

SECONDARY outcome

Timeframe: 24 Weeks

Population: Safety population included all participants who received study drug and had post-dose safety data available.

An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	29 participants	76 participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	5 participants	12 participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Safety population included all participants who received study drug and had post-dose safety data available.

The number of participants who stopped using the study drug because of an AE or a SAE. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With AE and SAE Related Discontinuation Discontinuation due to AE	8 participants	7 participants
Number of Participants With AE and SAE Related Discontinuation Discontinuation due to SAE	5 participants	6 participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Safety population included all participants who received study drug and had post-dose safety data available.

A serious infection was an infection that qualified as a Serious Adverse Event (SAE). A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Serious Infections	1 participants	1 participants

SECONDARY outcome

Timeframe: Week 24

Population: Participants from the safety population, all participants who received study drug and had at least 1 post-dose safety assessment, with data available for analysis.

Blood was collected for aspartate aminotransferase (serum glutamic oxaloacetic transaminase) \[AST/SGOT\] and alanine aminotransferase (serum glutamic pyruvic transaminase) \[ALT/SGPT\], liver function tests, and were analyzed at a central laboratory. The number of participants with High AST (SGOT) or ALT (SGPT) levels at Week 24 is reported.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Elevated AST (SGOT) and ALT (SGPT) ALT (SGPT)	3 participants	6 participants
Number of Participants With Elevated AST (SGOT) and ALT (SGPT) AST (SGOT)	3 participants	8 participants

SECONDARY outcome

Timeframe: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24

Population: Safety population included all participants who received study drug and had post-dose safety data available.

Blood samples were collected for Total Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Desirable ( \< 200), Borderline High (200- 239) or High (≥ 240). The number of participants categorized Borderline High or High at each time-point is reported.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 0	10 participants	25 participants
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 4	16 participants	41 participants
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 8	10 participants	34 participants
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 12	9 participants	30 participants
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 16	10 participants	36 participants
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 20	7 participants	35 participants
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines Week 24	9 participants	30 participants

SECONDARY outcome

Timeframe: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24

Population: Safety population included all participants who received study drug and had post-dose safety data available.

Blood samples were collected for High Density Lipoprotein (HDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the HDL Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Low (\< 40) or High (≥ 60). The number of participants with category High at each time-point is reported.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=75 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 0	4 participants	20 participants
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 4	10 participants	34 participants
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 8	2 participants	26 participants
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 12	6 participants	22 participants
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 16	5 participants	19 participants
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 20	2 participants	20 participants
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines Week 24	5 participants	20 participants

SECONDARY outcome

Timeframe: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24

Population: Safety population included all participants who received study drug and had post-dose safety data available.

Blood samples were collected for Low Density Lipoprotein (LDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the LDL Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Optimal (\< 100), Near Optimal/Above Optimal (100- 129), Borderline High (130- 159), High (160-189) or Very High (≥ 190). The number of participants categorized Borderline High, High or Very High at each time-point is reported.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 0	9 participants	24 participants
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 4	11 participants	35 participants
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 8	7 participants	21 participants
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 12	8 participants	27 participants
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 16	9 participants	31 participants
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 20	7 participants	33 participants
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines Week 24	8 participants	29 participants

SECONDARY outcome

Timeframe: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24

Population: Safety population included all participants who received study drug and had post-dose safety data available.

Blood samples were collected for Triglyceride and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Triglyceride level in milligram/deciliter (mg/dL) was categorized as: Normal (\< 150), Borderline High (150- 199), High (200- 499) or Very High (≥ 500). The number of participants categorized Borderline High, High or Very High at each time-point is reported.

Outcome measures

Outcome measures
Measure	Tocilizumab n=29 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 Participants Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 0	4 participants	7 participants
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 4	6 participants	15 participants
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 8	4 participants	12 participants
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 12	5 participants	15 participants
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 16	6 participants	15 participants
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 20	8 participants	16 participants
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines Week 24	6 participants	16 participants

Adverse Events

Tocilizumab Monotherapy

Serious events: 5 serious events

Other events: 29 other events

Deaths: 0 deaths

Tocilizumab + MTX

Serious events: 12 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tocilizumab Monotherapy n=29 participants at risk Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions).	Tocilizumab + MTX n=76 participants at risk Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Reproductive system and breast disorders Dysfunctional uterine bleeding	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Infections and infestations Viremia	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Investigations Alanine aminotransferase increased	3.4% 1/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Investigations Aspartate aminotransferase increased	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Blood and lymphatic system disorders Leukopenia	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Blood and lymphatic system disorders Neutropenia	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	2.6% 2/76 Safety population included all participants who received study drug and had post-dose safety data available.
Infections and infestations Gangrene	3.4% 1/29 Safety population included all participants who received study drug and had post-dose safety data available.	0.00% 0/76 Safety population included all participants who received study drug and had post-dose safety data available.
Hepatobiliary disorders Hepatitis fulminant	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Investigations Blood bilirubin increased	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
General disorders Chest pain	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Vascular disorders Haematoma	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Infections and infestations Pilonidal cyst	3.4% 1/29 Safety population included all participants who received study drug and had post-dose safety data available.	0.00% 0/76 Safety population included all participants who received study drug and had post-dose safety data available.
Investigations C-reactive protein increased	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Cardiac disorders Cardiac arrest	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Musculoskeletal and connective tissue disorders Arthralgia	3.4% 1/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Musculoskeletal and connective tissue disorders Joint effusion	3.4% 1/29 Safety population included all participants who received study drug and had post-dose safety data available.	0.00% 0/76 Safety population included all participants who received study drug and had post-dose safety data available.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	3.4% 1/29 Safety population included all participants who received study drug and had post-dose safety data available.	0.00% 0/76 Safety population included all participants who received study drug and had post-dose safety data available.
Gastrointestinal disorders Diarrhoea	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
General disorders Oedema	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/29 Safety population included all participants who received study drug and had post-dose safety data available.	1.3% 1/76 Safety population included all participants who received study drug and had post-dose safety data available.