Trial Outcomes & Findings for The VOLTAIRE-X Trial Looks at the Effect of Switching Between Humira® and BI 695501 in Patients With Plaque Psoriasis (NCT NCT03210259)

Last Updated: 2021-07-14

Results Overview

Area Under the Plasma Concentration Time Curve Over the 2 weeks dosing Interval between Week 30 to 32 (AUCτ, 30-32) for Adalimumab in plasma was reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

259 participants

Primary outcome timeframe

Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Results posted on

2021-07-14

Participant Flow

This was a 58-week, multiple-dose, active comparator trial of BI 695501 and US-licensed Humira in patients with moderate to severe chronic plaque psoriasis. The trial consisted of a single-arm run-in period of 14 weeks for all patients, followed by a randomized, double-blind, 2-arm period of 34 weeks. The total treatment period was 48 weeks followed by 10 weeks of safety follow up (SFU).

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Not Randomized Patients received US-licensed Humira during the run-in period. A loading dose of 80 milligrams (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. At the beginning of Week 14, patients who achieved at least a 50 percent reduction in Psoriasis Area and Severity Index (PASI50) response were randomized in a 1:1 ratio to either a continuous arm receiving 40mg of US-licensed Humira every other week until week 48 or in a switching arm separated in 3 periods. Patients who participated in the run-in period but not being randomized after run-in period were included in this group.	Switching Arm (Post-Randomization Period) Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
12-Week Run-in Period STARTED	21	118	120
12-Week Run-in Period COMPLETED	0	118	120
12-Week Run-in Period NOT COMPLETED	21	0	0
48-Week Randomized Responder Period STARTED	0	118	120
48-Week Randomized Responder Period COMPLETED	0	107	91
48-Week Randomized Responder Period NOT COMPLETED	0	11	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Not Randomized Patients received US-licensed Humira during the run-in period. A loading dose of 80 milligrams (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. At the beginning of Week 14, patients who achieved at least a 50 percent reduction in Psoriasis Area and Severity Index (PASI50) response were randomized in a 1:1 ratio to either a continuous arm receiving 40mg of US-licensed Humira every other week until week 48 or in a switching arm separated in 3 periods. Patients who participated in the run-in period but not being randomized after run-in period were included in this group.	Switching Arm (Post-Randomization Period) Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
12-Week Run-in Period Adverse Event	1	0	0
12-Week Run-in Period Death	1	0	0
12-Week Run-in Period Withdrawal by Subject	9	0	0
12-Week Run-in Period Lost to Follow-up	4	0	0
12-Week Run-in Period Lack of Efficacy	6	0	0
48-Week Randomized Responder Period Missed study visit	0	1	2
48-Week Randomized Responder Period Lost to Follow-up	0	3	8
48-Week Randomized Responder Period Pregnancy	0	1	0
48-Week Randomized Responder Period Physician Decision	0	0	1
48-Week Randomized Responder Period Withdrawal by Subject	0	5	17
48-Week Randomized Responder Period Adverse Event	0	1	1

Baseline Characteristics

The VOLTAIRE-X Trial Looks at the Effect of Switching Between Humira® and BI 695501 in Patients With Plaque Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Switching Arm (Post-Randomization Period) n=118 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=120 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.	Total n=238 Participants Total of all reporting groups
Age, Continuous	46.1 Years STANDARD_DEVIATION 13.95 • n=5 Participants	43.7 Years STANDARD_DEVIATION 13.69 • n=7 Participants	44.9 Years STANDARD_DEVIATION 13.84 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	44 Participants n=7 Participants	81 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	76 Participants n=7 Participants	157 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=5 Participants	102 Participants n=7 Participants	202 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	113 Participants n=5 Participants	119 Participants n=7 Participants	232 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Population: The Pharmacokinetic (PK) Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.

Area Under the Plasma Concentration Time Curve Over the 2 weeks dosing Interval between Week 30 to 32 (AUCτ, 30-32) for Adalimumab in plasma was reported.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=102 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=93 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Area Under the Plasma Concentration Time Curve Over the Dosing Interval of Week 30 to 32 (AUCτ, 30-32) for Adalimumab in Plasma	2040 microgram * hours / milliliter Standard Deviation 1420	1980 microgram * hours / milliliter Standard Deviation 1600

PRIMARY outcome

Timeframe: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Population: The PK Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.

Maximum observed concentration during the 2 weeks dosing interval between Week 30 to 32 (Cmax, 30-32) for Adalimumab in plasma was reported.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=104 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=99 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Maximum Observed Concentration During the Dosing Interval Week 30-32 (Cmax, 30-32) for Adalimumab in Plasma	7.13 microgram / milliliter Standard Deviation 4.63	7.14 microgram / milliliter Standard Deviation 5.37

SECONDARY outcome

Timeframe: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Population: The PK Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.

Minimum Observed Concentration During the 2 weeks Dosing Interval between Week 30 to 32 (Cmin, 30-32) for Adalimumab in plasma was reported.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=104 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=98 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Minimum Observed Concentration During the Dosing Interval of Week 30 to 32 (Cmin, 30-32) for Adalimumab in Plasma	5.04 micogram / milliliter Standard Deviation 3.89	4.66 micogram / milliliter Standard Deviation 4.19

SECONDARY outcome

Timeframe: Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.

Population: The PK Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.

Time to Maximum Observed Concentration During the 2 weeks Dosing Interval between Week 30 to 32 (tmax, 30-32) for Adalimumab in plasma was reported.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=104 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=99 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Time to Maximum Observed Concentration During the Dosing Interval of Week 30 to 32 (Tmax, 30-32) for Adalimumab in Plasma	72.7 hours Interval 66.0 to 336.0	72.3 hours Interval 46.8 to 240.0

SECONDARY outcome

Timeframe: At week 32

Population: The PPS contained all patients from the TS who did not experience any important protocol violations relevant for efficacy. Missing data were imputed via non-responder imputation for patients who discontinued treatment early and multiple imputation (MI) for missing at random value. There were no cases where it was required to implement MI.

The PASI is an established measure of clinical efficacy for psoriasis medications. The PASI is a tool which provides a numeric scoring for patients' overall psoriasis disease state, with scores ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, trunk, upper extremities and lower extremities). Higher PASI scores indicate more severe psoriasis. PASI is generally summarized as a dichotomous outcome based on achieving over an X percent(%) reduction from baseline (or PASIX), where X is 50, 75, 90, and 100. Results are reported for percentage of patients with a PASI75 response at Week 32. Analysis was done on per-protocol analysis set (PPS).

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=118 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=119 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Percentage of Patients With a 75% Reduction in Psoriasis Area and Severity Index (PASI75) Response at Week 32	84.75 Percentage of patients	78.99 Percentage of patients

SECONDARY outcome

Timeframe: At week 32

The sPGA is a 5-point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment is considered "static", which refers to the patient's disease state at the time of the assessments, without comparison to any of the patient's previous disease states (dynamic), whether at baseline or at a previous visit. A lower score indicates less body coverage and a higher score indicates more severe disease (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe). Results are reported for percentage of patients with a sPGA score of ≤ 1 (clear or almost clear) at Week 32. Analysis was done on per-protocol analysis set (PPS).

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=118 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=119 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Percentage of Patients With a Static Physician's Global Assessment (sPGA) Score ≤ 1 (Clear or Almost Clear) at Week 32	70.34 Percentage of patients	64.71 Percentage of patients

SECONDARY outcome

Timeframe: Immunogenicity samples were collected pre-dose at Week 32.

Population: Patients in the TS who had non-missing endpoints. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.

Number of patients with a confirmed positive anti-drug antibody (ADA) response to Adalimumab (BI 695501 or Humira) at Week 32. A participant was considered "ADA positive" if the blank normalized signal in the ADA screening assay was equal to or above the study specific ADA screening cut point factor of 1.06 and the signal inhibition by drug in the ADA confirmatory assay was equal to or above the study specific ADA confirmatory cut points (11.4% for signal inhibition with Humira and 12.0% for signal inhibition with BI 695501).

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=112 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=112 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32 Negative	11 Participants	6 Participants
Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32 Positive	101 Participants	104 Participants
Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32 Total reportable	112 Participants	110 Participants
Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32 Not reportable	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Immunogenicity samples were collected pre-dose at Week 32.

Population: Patients in the TS who had non-missing endpoints. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.

Number of patients with a positive neutralizing anti-drug antibody (nAb) response to Adalimumab (BI 695501 or Humira) at Week 32. A participant was considered "nAb positive" if the blank normalized signal in the nAb screening assay was equal to or below the study specific nAb screening cut point factor of 0.836.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=112 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=112 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32 Not reportable	0 Participants	2 Participants
Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32 Negative	66 Participants	64 Participants
Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32 Positive	46 Participants	46 Participants
Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32 Total reportable	112 Participants	110 Participants

SECONDARY outcome

Timeframe: Immunogenicity samples were collected pre-dose at Week 32.

Population: Analysis was on patients in the treated set (TS) with positive ADA at week 32. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.

Anti-drug antibody (ADA) titer of patients with a confirmed positive ADA response to Adalimumab (BI 695501 or Humira) at Week 32.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=101 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=104 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Anti-drug Antibody (ADA) Titer of Patients With ADA at Week 32	64.0 Titer Interval 32.0 to 256.0	128 Titer Interval 16.0 to 256.0

SECONDARY outcome

Timeframe: Immunogenicity samples were collected pre-dose at Week 32.

Population: Analysis was on patients in the treated set (TS) with positive nAb at week 32. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.

Neutralizing anti-drug antibody (nAb) titer of patients with a positive nAb response to Adalimumab (BI 695501 or Humira) at Week 32.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=46 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=46 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Neutralizing Anti-drug Antibody (nAb) Titer of Patients With nAb at Week 32	2.0 Titer Interval 1.0 to 4.0	2.0 Titer Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: From first dose of trial post-randomization medication until 10 weeks after last dose of trial post-randomization medication, up to 44 weeks

Population: The Treated Set (TS) contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.

Analysis of AEs focused on treatment-emergent adverse events (TEAEs) and is presented here for the post-randomization period (Week 14 to 58). For the post-randomization period analysis, TEAEs were defined as AEs that started or worsened on or after the first dose of trial post-randomization medication and prior to the last dose of trial post-randomization medication + 10 weeks.

Outcome measures

Outcome measures
Measure	Switching Arm (Post-Randomization Period) n=118 Participants Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=120 Participants Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Percentage of Patients With Drug-related Adverse Events (AEs) During the Post-Randomization Period	11.9 Percentage of patients	18.3 Percentage of patients

Adverse Events

Humira Containing All RTS Subjects (Run-In Period)

Serious events: 6 serious events

Other events: 24 other events

Deaths: 1 deaths

Switching Arm (Post-Randomization Period)

Serious events: 5 serious events

Other events: 17 other events

Deaths: 0 deaths

Continuous Humira (Post-Randomization Period)

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Humira Containing All RTS Subjects (Run-In Period) n=259 participants at risk All patients received US-licensed Humira during the run-in period of 14 weeks (Period 1). Patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). All patients in the run-in period were in this group including those who were randomised and who did not being randomised after the run-in period.	Switching Arm (Post-Randomization Period) n=118 participants at risk Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the switching arm were included in this group.	Continuous Humira (Post-Randomization Period) n=120 participants at risk Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL). Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.
Infections and infestations Nasopharyngitis	6.2% 16/259 • From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period). Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.	9.3% 11/118 • From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period). Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.	4.2% 5/120 • From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period). Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.
Nervous system disorders Headache	3.9% 10/259 • From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period). Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.	5.1% 6/118 • From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period). Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.	5.0% 6/120 • From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period). Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.

Additional Information

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