Trial Outcomes & Findings for A Study to Compare FKB327 Long-term Safety, Efficacy and Immunogenicity With Humira® in Rheumatoid Arthritis Patients (NCT NCT02405780)

Last Updated: 2019-03-26

Results Overview

Period II: at week 30 all patients were transferred to receive FKB327. Each subject was counted once within each System Organ Class (SOC) and Preferred Term (PT). Death defined as a fatal outcome of a (S)AE. SAEs were followed until resolution, the investigator confirmed the event was unlikely to resolve or the patient was lost to follow-up.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

645 participants

Primary outcome timeframe

Period II: from Week 30 up to Week 80

Results posted on

2019-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	FKB327-FKB327-FKB327 Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F). Period II: From week 30 all subjects received FKB327; (F-F-F).	FKB327-Humira-FKB327 Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H). Period II: From week 30 all subjects received FKB327; (F-H-F).	Humira-FKB327-FKB327 Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F). Period II: From week 30 all subjects received FKB327; (H-F-F).	Humira-Humira-FKB327 Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H). Period II: From week 30 all subjects received FKB327; (H-H-F).
Period I STARTED	216	108	108	213
Period I COMPLETED	189	100	93	190
Period I NOT COMPLETED	27	8	15	23
Period II STARTED	189	100	93	190
Period II COMPLETED	174	88	81	172
Period II NOT COMPLETED	15	12	12	18

Reasons for withdrawal

Reasons for withdrawal
Measure	FKB327-FKB327-FKB327 Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F). Period II: From week 30 all subjects received FKB327; (F-F-F).	FKB327-Humira-FKB327 Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H). Period II: From week 30 all subjects received FKB327; (F-H-F).	Humira-FKB327-FKB327 Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F). Period II: From week 30 all subjects received FKB327; (H-F-F).	Humira-Humira-FKB327 Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H). Period II: From week 30 all subjects received FKB327; (H-H-F).
Period I Adverse Event	8	0	3	7
Period I Medical reasons	1	1	0	1
Period I Screening Failure	1	0	1	0
Period I Withdrawal by Subject	9	1	3	4
Period I Non-compliance with study procedures	8	6	8	11
Period II Adverse Event	3	5	4	11
Period II Medical reason	0	1	0	0
Period II Pregnancy	0	0	1	0
Period II Withdrawal by Subject	7	4	0	3
Period II Non-compliance with study procedures	5	2	7	4

Baseline Characteristics

A Study to Compare FKB327 Long-term Safety, Efficacy and Immunogenicity With Humira® in Rheumatoid Arthritis Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FKB327-FKB327 n=216 Participants This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003.	FKB327-Humira n=108 Participants This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003.	Humira-FKB327 n=108 Participants This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive FKB327 in Study FKB327-003.	Humira-Humira n=213 Participants This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to receive the reference product Humira in Study FKB327-003.	Total n=645 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	183 Participants n=5 Participants	92 Participants n=7 Participants	96 Participants n=5 Participants	169 Participants n=4 Participants	540 Participants n=21 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	44 Participants n=4 Participants	105 Participants n=21 Participants
Sex: Female, Male Female	162 Participants n=5 Participants	85 Participants n=7 Participants	83 Participants n=5 Participants	171 Participants n=4 Participants	501 Participants n=21 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	23 Participants n=7 Participants	25 Participants n=5 Participants	42 Participants n=4 Participants	144 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) White	187 Participants n=5 Participants	90 Participants n=7 Participants	90 Participants n=5 Participants	185 Participants n=4 Participants	552 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants	17 Participants n=7 Participants	15 Participants n=5 Participants	25 Participants n=4 Participants	83 Participants n=21 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment Chile	13 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants	40 Participants n=21 Participants
Region of Enrollment Czechia	22 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants	22 Participants n=4 Participants	64 Participants n=21 Participants
Region of Enrollment Germany	7 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	22 Participants n=21 Participants
Region of Enrollment Peru	26 Participants n=5 Participants	17 Participants n=7 Participants	15 Participants n=5 Participants	26 Participants n=4 Participants	84 Participants n=21 Participants
Region of Enrollment Poland	41 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	39 Participants n=4 Participants	124 Participants n=21 Participants
Region of Enrollment Romania	8 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	23 Participants n=21 Participants
Region of Enrollment Russia	33 Participants n=5 Participants	18 Participants n=7 Participants	16 Participants n=5 Participants	29 Participants n=4 Participants	96 Participants n=21 Participants
Region of Enrollment Spain	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	9 Participants n=21 Participants
Region of Enrollment Ukraine	39 Participants n=5 Participants	14 Participants n=7 Participants	17 Participants n=5 Participants	37 Participants n=4 Participants	107 Participants n=21 Participants
Region of Enrollment United States	24 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	24 Participants n=4 Participants	71 Participants n=21 Participants

PRIMARY outcome

Timeframe: Period I: from Week 0 up until Week 30;

Population: Each patient was counted once within each System Organ Class (SOC) and Preferred Term (PT). A patient may have had multiple events counted. Treatment Emergen Adverse Events (TEAE) defined as AEs that started or increased in severity after the first study dose and counted under the treatment arm.

Period I: Patients were carefully monitor for Adverse Events from signing of informed consent until week 30 and thereafter during Period II of the study. For patients who discontinued early, a follow-up period of 4 weeks was added to the Early Termination Visit. The investigator actively asked the patients for Adverse Events. Patients spontaneously reported Adverse Events to the Investigator during clinic visits or in between visits.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I Death	0 participants	0 participants	1 participants	1 participants	—
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I Treatment Emergent Deaths	0 participants	0 participants	1 participants	1 participants	—
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I At least 1 TEAE	103 participants	59 participants	59 participants	117 participants	—
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I At least 1 severe TEAE	5 participants	2 participants	3 participants	2 participants	—
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I At least 1 treatment related TEAE	39 participants	21 participants	27 participants	49 participants	—
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I Premature Discontinuation due to a TEAE	10 participants	0 participants	4 participants	11 participants	—
Number of Patients With Adverse Events as a Measure of Safety Per Treatment Group in Period I Treatment Interruption due to a TEAE	19 participants	9 participants	14 participants	20 participants	—

PRIMARY outcome

Timeframe: Period II: from Week 30 up to Week 80

From week 30 all subjects were transferred to receive FKB327 treatment. Adverse Events were contentiously monitored and recorded during Period II. For patients discontinuing the study prematurely, a follow-up period of 4 weeks was added to the Early Termination Visit. The data for Period II is based on the number of patients in the Safety Analysis Set that entered Period II.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=572 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period Death	2 Participants	—	—	—	—
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period Treatment Emergent Deaths	2 Participants	—	—	—	—
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period At least 1 TEAE	340 Participants	—	—	—	—
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period At least 1 severe TEAE	19 Participants	—	—	—	—
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period At least 1 treatment related TEAE	126 Participants	—	—	—	—
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period Premature Discontinuation due to a TEAE	25 Participants	—	—	—	—
Number of Patients With Adverse Events as a Measure of Safety in Period II - Single Treatment Period Treatment Interruption due to a TEAE	36 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Period I: from Week 0 up until Week 30

Population: Each patient was counted once within each System Organ Class (SOC) and Preferred Term (PT). Death defined as a fatal outcome of a (S) AE.

A Serious Adverse Event (SAE) was defined in the Protocol as: Death; or a Life-threatening Adverse Event (AE); Inpatient Hospitalization; Persistant or significant disability or incapacity; A congenital anomaly/birth defect; An important medical event that may not have resulted in death, have been life-threatening, or required hospitalization, but may have jeopardized the patient and may have required medical intervention to prevent 1 of the outcomes listed in this definition. SAEs were followed until resolution, the investigator confirmed the event was unlikely to resolve or the patient was recorded as lost to follow-up.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I Deaths	0 participants	0 participants	1 participants	1 participants	—
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I Treatment Emergent Deaths	0 participants	0 participants	1 participants	1 participants	—
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I Treatment Discontinuation due to a TESAE	0 participants	0 participants	0 participants	2 participants	—
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I Treatment Interruption due to a TESAE	3 participants	2 participants	4 participants	2 participants	—
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I At least 1 TESAE	5 participants	7 participants	5 participants	7 participants	—
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I Number of TESAE	7 participants	9 participants	9 participants	7 participants	—
Number of Patients With Serious Adverse Events as a Measure of Safety Per Treatment Group in Period I At least 1 SAE	5 participants	7 participants	5 participants	7 participants	—

PRIMARY outcome

Timeframe: Period II: from Week 30 up to Week 80

Population: Each patient was counted once within each System Organ Class (SOC) and Preferred Term (PT). Death defined as a fatal outcome of a (S) AE.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=572 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period Death	2 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period At least 1 TESAE	33 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period Number of TESAE	45 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period Treatment Emergent Deaths	2 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period At least 1 severe TEAE	19 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period Treatment Discontinuation due to a TESEA	10 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period Treatment Interruption due to a TESAE	6 Participants	—	—	—	—
Number of Patients With Serious Adverse Events as a Measure of Safety in Period II - Single Treatment Period At least 1 SAE	33 Participants	—	—	—	—

PRIMARY outcome

Timeframe: From Week 0 to Week 80

Population: The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visit is the number of patients who at a given timepoint had a measurement completed for the Safety Analysis Set.

Systolic Blood Pressure is part of Vital Signs which were part of the subject safety evaluations. Systolic Blood Pressure was measured at the following time-points: Week 0, Week 4, Week 8, Week 12, Week 24 and Week 80/End o Study (EOS). Systolic Blood Pressure with changes from Baseline\_002 (NCT022600791) was summarized by treatment sequence over the whole study period for each visit. Baseline\_002 is defined as the last non-missing measurement collected prior to the first study medication administered at Week 0 from Study FKB327-002.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Baseline_002	125.0 mmHg Interval 86.0 to 168.0	125.5 mmHg Interval 94.0 to 174.0	131.0 mmHg Interval 88.0 to 167.0	129.0 mmHg Interval 90.0 to 162.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Week 0	125.0 mmHg Interval 84.0 to 166.0	123.5 mmHg Interval 90.0 to 160.0	127.0 mmHg Interval 98.0 to 179.0	125.0 mmHg Interval 90.0 to 163.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Changes from Baseline_002 at week 0	0.0 mmHg Interval -34.0 to 35.0	-2.0 mmHg Interval -30.0 to 32.0	-2.0 mmHg Interval -44.0 to 32.0	-2.0 mmHg Interval -50.0 to 51.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Week 4	124.0 mmHg Interval 82.0 to 172.0	125.0 mmHg Interval 95.0 to 164.0	124.0 mmHg Interval 92.0 to 186.0	125 mmHg Interval 94.0 to 167.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Changes from Baseline_002 at week 4	0.0 mmHg Interval -56.0 to 38.0	0.0 mmHg Interval -22.0 to 44.0	-6.0 mmHg Interval -39.0 to 39.0	-1.0 mmHg Interval -37.0 to 36.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Week 8	124.0 mmHg Interval 88.0 to 154.0	124.0 mmHg Interval 89.0 to 153.0	128.0 mmHg Interval 92.0 to 160.0	125.0 mmHg Interval 92.0 to 156.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Changes from Baseline_002 at week 8	-2.0 mmHg Interval -47.0 to 32.0	-0.5 mmHg Interval -28.0 to 41.0	-1.5 mmHg Interval -35.0 to 30.0	-2.0 mmHg Interval -38.0 to 36.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Week 12	125.0 mmHg Interval 91.0 to 159.0	124.5 mmHg Interval 86.0 to 165.0	126.0 mmHg Interval 89.0 to 167.0	125.0 mmHg Interval 92.0 to 170.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Changes from Baseline_002 at week 12	0.0 mmHg Interval -35.0 to 45.0	-2.0 mmHg Interval -40.0 to 35.0	-2.0 mmHg Interval -44.0 to 28.0	0.0 mmHg Interval -46.0 to 40.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Week 24	125.0 mmHg Interval 90.0 to 155.0	127.5 mmHg Interval 92.0 to 156.0	125.0 mmHg Interval 86.0 to 163.0	126.0 mmHg Interval 94.0 to 176.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Changes from Baseline_002 at week 24	-2.0 mmHg Interval -46.0 to 36.0	0.0 mmHg Interval -38.0 to 33.0	-5.0 mmHg Interval -44.0 to 28.0	0.0 mmHg Interval -49.0 to 37.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Week 80/EOS	126.0 mmHg Interval 90.0 to 157.0	125.0 mmHg Interval 88.0 to 171.0	126.0 mmHg Interval 91.0 to 163.0	125.0 mmHg Interval 98.0 to 163.0	—
Changes in Vital Signs as a Measure of Safety - Systolic Blood Pressure Changes from Baseline_002 at week 80/EOS	-0.5 mmHg Interval -53.0 to 53.0	0.0 mmHg Interval -37.0 to 41.0	-2.0 mmHg Interval -47.0 to 27.0	-1.5 mmHg Interval -42.0 to 26.0	—

PRIMARY outcome

Timeframe: From Week 0 to Week 80

Diastolic Blood Pressure is part of Vital Signs which were part of the subject safety evaluations. Diastolic Blood Pressure was measured at the following time-points: Week 0, Week 4, Week 8, Week 12, Week 24 and Week 80/End o Study (EOS). Diastolic Blood Pressure with changes from Baseline\_002 (NCT022600791) was summarized by treatment sequence over the whole study period for each visit measured. Baseline\_002 is defined as the last non-missing measurement collected prior to the first study medication administered at Week 0 from Study FKB327-002.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Baseline_002	78.0 mmHg Interval 48.0 to 99.0	78.0 mmHg Interval 56.0 to 98.0	80.0 mmHg Interval 54.0 to 96.0	77.0 mmHg Interval 55.0 to 105.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Week 0	78.0 mmHg Interval 49.0 to 94.0	75.0 mmHg Interval 53.0 to 102.0	77.0 mmHg Interval 57.0 to 108.0	76.0 mmHg Interval 50.0 to 99.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Changes from Baseline_002 at week 0	0.0 mmHg Interval -23.0 to 28.0	-1.5 mmHg Interval -25.0 to 22.0	-1.0 mmHg Interval -25.0 to 24.0	0.0 mmHg Interval -31.0 to 23.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Week 4	76.0 mmHg Interval 51.0 to 94.0	77.0 mmHg Interval 59.0 to 96.0	76.0 mmHg Interval 58.0 to 107.0	78.0 mmHg Interval 55.0 to 100.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Changes from Baseline_002 at week 4	0.0 mmHg Interval -33.0 to 28.0	0.0 mmHg Interval -18.0 to 36.0	0.0 mmHg Interval -22.0 to 25.0	0.0 mmHg Interval -27.0 to 30.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Week 8	78.0 mmHg Interval 59.0 to 97.0	78.0 mmHg Interval 58.0 to 99.0	80.0 mmHg Interval 57.0 to 97.0	77.0 mmHg Interval 51.0 to 95.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Changes from Baseline_002 at week 8	0.0 mmHg Interval -26.0 to 26.0	0.0 mmHg Interval -23.0 to 34.0	0.0 mmHg Interval -18.0 to 15.0	0.0 mmHg Interval -30.0 to 21.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Week 12	78.0 mmHg Interval 52.0 to 98.0	78.5 mmHg Interval 56.0 to 104.0	80.0 mmHg Interval 58.0 to 103.0	78.0 mmHg Interval 58.0 to 95.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Changes from Baseline_002 at week 12	0.0 mmHg Interval -26.0 to 23.0	0.0 mmHg Interval -24.0 to 21.0	0.0 mmHg Interval -15.0 to 31.0	0.0 mmHg Interval -26.0 to 20.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Week 24	78.0 mmHg Interval 52.0 to 96.0	78.0 mmHg Interval 52.0 to 99.0	78.0 mmHg Interval 50.0 to 104.0	78.0 mmHg Interval 55.0 to 96.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Changes from Baseline_002 at week 24	1.0 mmHg Interval -22.0 to 25.0	0.0 mmHg Interval -24.0 to 19.0	0.0 mmHg Interval -22.0 to 16.0	0.0 mmHg Interval -36.0 to 18.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Week 80/EOS	78.0 mmHg Interval 41.0 to 98.0	79.0 mmHg Interval 60.0 to 100.0	80.0 mmHg Interval 56.0 to 102.0	77.0 mmHg Interval 50.0 to 95.0	—
Changes in Vital Signs as a Measure of Safety - Diastolic Blood Pressure Changes from Baseline_002 at week 80/EOS	0.0 mmHg Interval -42.0 to 30.0	0.0 mmHg Interval -32.0 to 24.0	0.0 mmHg Interval -25.0 to 18.0	0.0 mmHg Interval -48.0 to 20.0	—

PRIMARY outcome

Timeframe: From Week 0 to Week 80

Population: The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visits is the number of patients who at a given time point had a measurement completed for the Safety Analysis Set.

Pulse rate is part of Vital Signs which were part of the subject safety evaluations. Pulse rate was measured at the following time-points: Weeks 0, 4, 8, 12, 24 and 80/End of Study (EOS). Pulse Rate with changes from Baseline\_002 (NCT022600791) was summarized by treatment sequence over the whole study period for each visit. Baseline\_002 is defined as the last non-missing measurement collected prior to the first study medication administered at Week 0 from Study FKB327-002.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Changes in Vital Signs as a Measure of Safety - Pulse Rate Changes from Baseline_002 at week 12	-2.0 Beats per minute (bpm) Interval -36.0 to 30.0	-1.5 Beats per minute (bpm) Interval -31.0 to 18.0	-1.0 Beats per minute (bpm) Interval -28.0 to 25.0	-2.0 Beats per minute (bpm) Interval -30.0 to 19.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Week 12	71.0 Beats per minute (bpm) Interval 50.0 to 98.0	72.0 Beats per minute (bpm) Interval 56.0 to 100.0	72.0 Beats per minute (bpm) Interval 57.0 to 97.0	71.0 Beats per minute (bpm) Interval 52.0 to 92.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Baseline_002	74.0 Beats per minute (bpm) Interval 51.0 to 100.0	74.0 Beats per minute (bpm) Interval 54.0 to 97.0	74.0 Beats per minute (bpm) Interval 54.0 to 102.0	74.0 Beats per minute (bpm) Interval 53.0 to 106.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Week 0	72.0 Beats per minute (bpm) Interval 50.0 to 102.0	71.0 Beats per minute (bpm) Interval 48.0 to 94.0	72.0 Beats per minute (bpm) Interval 53.0 to 110.0	72.0 Beats per minute (bpm) Interval 42.0 to 99.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Changes from Baseline_002 at week 0	-0.5 Beats per minute (bpm) Interval -32.0 to 28.0	-3.0 Beats per minute (bpm) Interval -28.0 to 24.0	-3.0 Beats per minute (bpm) Interval -23.0 to 44.0	-2.0 Beats per minute (bpm) Interval -36.0 to 29.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Week 4	72.0 Beats per minute (bpm) Interval 47.0 to 112.0	72.0 Beats per minute (bpm) Interval 52.0 to 94.0	74.0 Beats per minute (bpm) Interval 51.0 to 105.0	72.0 Beats per minute (bpm) Interval 50.0 to 102.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Changes from Baseline_002 at week 4	-2.0 Beats per minute (bpm) Interval -29.0 to 24.0	-2.0 Beats per minute (bpm) Interval -28.0 to 24.0	-2.0 Beats per minute (bpm) Interval -24.0 to 30.0	-1.0 Beats per minute (bpm) Interval -37.0 to 32.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Week 8	72.0 Beats per minute (bpm) Interval 53.0 to 99.0	72.0 Beats per minute (bpm) Interval 54.0 to 102.0	72.0 Beats per minute (bpm) Interval 53.0 to 100.0	72 Beats per minute (bpm) Interval 46.0 to 99.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Changes from Baseline_002 at week 8	0.0 Beats per minute (bpm) Interval -41.0 to 26.0	-2.0 Beats per minute (bpm) Interval -26.0 to 32.0	-2.0 Beats per minute (bpm) Interval -28.0 to 19.0	-2.0 Beats per minute (bpm) Interval -37.0 to 25.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Week 24	73.0 Beats per minute (bpm) Interval 50.0 to 103.0	72.0 Beats per minute (bpm) Interval 55.0 to 96.0	72.0 Beats per minute (bpm) Interval 58.0 to 99.0	72.0 Beats per minute (bpm) Interval 49.0 to 95.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Changes from Baseline_002 at week 24	0.0 Beats per minute (bpm) Interval -35.0 to 26.0	-2.0 Beats per minute (bpm) Interval -33.0 to 20.0	-2.0 Beats per minute (bpm) Interval -29.0 to 26.0	-2.0 Beats per minute (bpm) Interval -32.0 to 34.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Week 80/EOS	74.0 Beats per minute (bpm) Interval 52.0 to 110.0	72.0 Beats per minute (bpm) Interval 55.0 to 94.0	72.0 Beats per minute (bpm) Interval 50.0 to 96.0	73.5 Beats per minute (bpm) Interval 45.0 to 111.0	—
Changes in Vital Signs as a Measure of Safety - Pulse Rate Changes from Baseline_002 at week 80/EOS	-1.0 Beats per minute (bpm) Interval -31.0 to 32.0	-2.0 Beats per minute (bpm) Interval -30.0 to 19.0	-1.0 Beats per minute (bpm) Interval -25.0 to 26.0	-1.0 Beats per minute (bpm) Interval -37.0 to 31.0	—

PRIMARY outcome

Timeframe: From Week 0 to Week 80

Population: The number of patients in the Safety Analysis Set; is equal to the number of patients who entered Period I. The number of patients at the following visits is the number of patients who at a given timepoint had a measurement completed for the Safety Analysis Set.

Temperature measurements forms part of the vital signs which was one of the continuous safety measurements for the study primary endpoint. Temperature was measured at week 0, week 4, week 8, week 12, week 24 and at week 80 or at End of Study (EOS). Temperature with change from Baseline\_002 were summarized by treatment sequence over the whole study period. Baseline\_002 is defined as the last non-missing measurement collected prior to the first study medication administration at Week 0 from Study FKB327-002 (NCT02260791).

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Changes from Baseline_002 at week 0	0.000 Centigrades Interval -0.8 to 1.19	0.000 Centigrades Interval -1.2 to 0.7	0.000 Centigrades Interval -0.7 to 1.0	0.000 Centigrades Interval -1.0 to 0.8	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Baseline_002	36.600 Centigrades Interval 35.61 to 37.2	36.600 Centigrades Interval 35.5 to 37.0	36.600 Centigrades Interval 35.6 to 37.3	36.500 Centigrades Interval 35.6 to 37.6	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Week 0	36.500 Centigrades Interval 35.7 to 37.2	36.500 Centigrades Interval 35.5 to 37.1	36.600 Centigrades Interval 35.56 to 37.2	36.500 Centigrades Interval 35.7 to 37.1	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Week 4	36.500 Centigrades Interval 34.56 to 37.7	36.500 Centigrades Interval 35.7 to 37.0	36.500 Centigrades Interval 35.2 to 37.11	36.500 Centigrades Interval 35.6 to 37.2	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Changes from Baseline_002 at week 4	0.000 Centigrades Interval -1.94 to 1.4	0.000 Centigrades Interval -0.7 to 1.2	-0.100 Centigrades Interval -1.2 to 1.0	0.000 Centigrades Interval -1.2 to 1.0	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Week 8	36.500 Centigrades Interval 35.0 to 37.28	36.500 Centigrades Interval 35.4 to 37.2	36.500 Centigrades Interval 35.6 to 37.2	36.500 Centigrades Interval 35.5 to 37.3	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Changes from Baseline_002 at week 8	0.000 Centigrades Interval -1.5 to 1.19	-0.100 Centigrades Interval -0.83 to 1.1	-0.025 Centigrades Interval -0.7 to 0.8	0.000 Centigrades Interval -1.4 to 1.2	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Week 12	36.500 Centigrades Interval 35.56 to 37.2	36.500 Centigrades Interval 35.1 to 37.1	36.500 Centigrades Interval 35.4 to 37.0	36.500 Centigrades Interval 35.6 to 37.4	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Changes from Baseline_002 at week 12	0.000 Centigrades Interval -0.94 to 0.8	0.000 Centigrades Interval -1.1 to 0.8	-0.100 Centigrades Interval -1.1 to 0.9	0.000 Centigrades Interval -1.6 to 1.3	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Week 24	36.500 Centigrades Interval 35.5 to 37.2	36.500 Centigrades Interval 35.5 to 37.9	36.500 Centigrades Interval 35.6 to 37.4	36.500 Centigrades Interval 35.6 to 37.2	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Changes from Baseline_002 at week 24	0.000 Centigrades Interval -1.0 to 1.0	0.000 Centigrades Interval -0.9 to 1.4	0.000 Centigrades Interval -0.9 to 1.0	0.000 Centigrades Interval -1.1 to 0.8	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Week 80/EOS	36.500 Centigrades Interval 35.6 to 37.3	36.500 Centigrades Interval 35.7 to 37.1	36.500 Centigrades Interval 35.3 to 37.0	36.500 Centigrades Interval 35.5 to 37.3	—
Changes in Vital Signs as a Measure of Safety - Temperature Measurements Changes from Baseline_002 at week 80/EOS	0.000 Centigrades Interval -1.1 to 1.19	0.000 Centigrades Interval -0.8 to 0.9	-0.100 Centigrades Interval -1.0 to 0.7	0.000 Centigrades Interval -1.0 to 0.9	—

PRIMARY outcome

Timeframe: From Week 0 to Week 80

Clinical Laboratory tests for hematology and serum chemistry were performed by the sites and analysed at a Central Laboratory. Urine dip-stick tests were performed by the sites. Laboratory samples were taken at the following time-points (weeks): 0; 4; 8; 12; 24; 30; 42; 54; 66; 76 and 80/End of Study (EOS). Each result outside its normal range was review and assessed by the investigator whether or not it was Clinically Significant (CS) or Not Clinically Significant (NCS) CS laboratory abnormalities were recorded as AEs.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II n=572 Participants From Week 30 all patients were treated with FKB327
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Neutropenia	3 participants	0 participants	0 participants	1 participants	2 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Hypercholesterolaemia	3 participants	3 participants	2 participants	3 participants	2 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) ALT increased	3 participants	2 participants	0 participants	1 participants	10 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Anaemia	3 participants	1 participants	2 participants	3 participants	11 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Leukopenia	3 participants	1 participants	0 participants	0 participants	2 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) AST increased	3 participants	0 participants	0 participants	1 participants	7 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Dyslipidaemia	1 participants	0 participants	1 participants	1 participants	8 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) CRP increased	0 participants	0 participants	0 participants	1 participants	8 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Latent TB	3 participants	0 participants	4 participants	4 participants	10 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Mycobacterium tuberculosis complex test positive	7 participants	2 participants	2 participants	6 participants	5 participants
Summary of Most Common Clinical Significant Laboratory Parameters Reported as Adverse Events (Reported by ≥1% of the Patients) Haematuria	1 participants	0 participants	2 participants	2 participants	2 participants

SECONDARY outcome

Timeframe: From Week 0 of FKB327-002 to Week 80

Population: DAS28-CRP and change from Baseline in Study FKB327-002 (i.e. Baseline\_002) in DAS28-CRP were summarized by overall treatment sequence and visit as well as by treatment for each period (Period I and Period II)

The DAS28 score is a combined index that has been developed to measure the disease activity in patients with Rheumatoid arthritis (RA) and has been extensively validated for the use in clinical studies. The DAS28-CRP assessment involved evaluating the number of tender (TJC) and the swollen (SJC) joints (out of 28 specified joints), serum CRP, and patient global assessment of disease activity (Visual analogue scale (VAS) from 0-100, very well to extremely bad). The individual results are summarized using a formula. DAS28 is a number on a scale from 0 to 10 indicating the current activity of the patient's RA. A higher score indicates higher disease activity. During the FKB327-003 study for Period I and Period II the DAS28-CRP score was compared to Baseline in study FKB327-002 (NCT02260791).

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Baseline_002	6.02 units on a scale Interval 3.3 to 8.1	6.12 units on a scale Interval 2.9 to 8.5	5.99 units on a scale Interval 3.7 to 7.9	6.11 units on a scale Interval 4.0 to 8.0	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 0	3.46 units on a scale Interval 1.2 to 7.3	3.49 units on a scale Interval 1.2 to 7.4	3.65 units on a scale Interval 1.2 to 7.2	3.36 units on a scale Interval 1.2 to 7.0	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 0 change from Baseline	-2.56 units on a scale Interval -5.7 to 1.0	-2.63 units on a scale Interval -6.4 to 1.2	-2.33 units on a scale Interval -5.4 to 0.9	-2.75 units on a scale Interval -5.7 to 1.3	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 4	3.33 units on a scale Interval 1.2 to 7.0	3.37 units on a scale Interval 1.2 to 7.0	3.53 units on a scale Interval 1.3 to 6.7	3.29 units on a scale Interval 1.2 to 7.6	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 4 change from Baseline	-2.64 units on a scale Interval -6.1 to 1.8	-2.76 units on a scale Interval -6.9 to 0.9	-2.48 units on a scale Interval -4.9 to 1.6	-2.81 units on a scale Interval -6.1 to 1.8	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 8	3.28 units on a scale Interval 1.2 to 7.2	3.37 units on a scale Interval 1.2 to 6.9	3.51 units on a scale Interval 1.2 to 6.6	3.25 units on a scale Interval 1.2 to 7.1	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 8 change from Baseline	-2.72 units on a scale Interval -5.9 to 2.7	-2.74 units on a scale Interval -6.9 to 0.8	-2.47 units on a scale Interval -4.8 to 0.9	-2.84 units on a scale Interval -5.8 to -0.2	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 12	3.31 units on a scale Interval 1.2 to 6.9	3.30 units on a scale Interval 1.2 to 7.1	3.40 units on a scale Interval 1.3 to 6.2	3.21 units on a scale Interval 1.2 to 6.5	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 12 change from Baseline	-2.70 units on a scale Interval -5.9 to 0.8	-2.80 units on a scale Interval -6.9 to 0.3	-2.57 units on a scale Interval -4.9 to 0.5	-2.88 units on a scale Interval -5.8 to 0.9	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 24	3.13 units on a scale Interval 1.2 to 7.8	3.27 units on a scale Interval 1.2 to 7.1	3.40 units on a scale Interval 1.2 to 7.7	3.07 units on a scale Interval 1.2 to 7.5	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 24 change from Baseline	-2.89 units on a scale Interval -6.1 to 1.3	-2.86 units on a scale Interval -6.7 to 0.9	-2.57 units on a scale Interval -5.4 to 1.7	-3.04 units on a scale Interval -6.0 to 0.0	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Period II: Week 30	3.04 units on a scale Interval 1.2 to 7.1	3.28 units on a scale Interval 1.2 to 7.1	3.20 units on a scale Interval 1.3 to 6.3	3.13 units on a scale Interval 1.2 to 7.4	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 30 change from Baseline	-2.99 units on a scale Interval -6.1 to 0.3	-2.84 units on a scale Interval -6.6 to 0.5	-2.78 units on a scale Interval -5.3 to 0.4	-2.95 units on a scale Interval -6.2 to 1.9	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 42	3.05 units on a scale Interval 1.2 to 6.8	3.28 units on a scale Interval 1.2 to 6.1	3.08 units on a scale Interval 1.3 to 6.0	3.07 units on a scale Interval 1.2 to 7.3	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy week 42 change from Baseline	-2.97 units on a scale Interval -5.6 to 0.9	-2.83 units on a scale Interval -6.2 to -0.2	-2.88 units on a scale Interval -5.5 to 0.0	-3.01 units on a scale Interval -5.8 to 0.6	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 54	3.04 units on a scale Interval 1.2 to 7.5	3.22 units on a scale Interval 1.2 to 6.2	3.26 units on a scale Interval 1.2 to 6.2	2.96 units on a scale Interval 1.2 to 6.8	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 54 change from Baseline	-2.99 units on a scale Interval -5.9 to 0.4	-2.90 units on a scale Interval -6.2 to 0.9	-2.70 units on a scale Interval -5.4 to 0.4	-3.12 units on a scale Interval -5.6 to 1.6	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 66	2.96 units on a scale Interval 1.2 to 7.0	3.17 units on a scale Interval 1.2 to 5.7	3.09 units on a scale Interval 1.3 to 5.6	2.91 units on a scale Interval 1.2 to 6.9	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 66 change from Baseline	-3.09 units on a scale Interval -5.9 to 0.3	-2.96 units on a scale Interval -6.9 to 0.0	-2.83 units on a scale Interval -5.5 to 0.8	-3.15 units on a scale Interval -5.6 to 0.2	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 76	2.97 units on a scale Interval 1.2 to 7.8	3.02 units on a scale Interval 1.2 to 6.2	3.12 units on a scale Interval 1.3 to 7.0	2.94 units on a scale Interval 1.2 to 6.4	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 76 change from Baseline	-3.04 units on a scale Interval -5.9 to 0.2	-3.11 units on a scale Interval -6.1 to 0.4	-2.79 units on a scale Interval -5.5 to 1.0	-3.14 units on a scale Interval -5.7 to -0.2	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 80	2.98 units on a scale Interval 1.2 to 7.1	3.09 units on a scale Interval 1.2 to 6.9	3.25 units on a scale Interval 1.2 to 6.7	3.06 units on a scale Interval 1.2 to 6.7	—
Changes in Disease Activity Score 28 Based on C Reactive Protein (DAS28 CRP) Score Compared to Baseline as a Measure of Efficacy Week 80 change from Baseline	-3.05 units on a scale Interval -6.2 to 2.2	-3.05 units on a scale Interval -6.9 to -0.3	-2.66 units on a scale Interval -5.4 to 0.2	-3.02 units on a scale Interval -5.8 to 0.2	—

SECONDARY outcome

Timeframe: From Week 0 to Week 80

Population: Number of patients at a given time-point with an observed ACR20 score defined as a 20% improvement in tender and swollen joints and at least 3 out of 5 other indicators from Baseline\_002 (Week 0 of FKB327-002; NCT02260791)

An ACR20 response means that the patient achieved a 20% improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and a 20% improvement in at least 3 of the other 5 Core Data Set elements listed below: * Acute phase reactant (C-reactive protein, CRP) A high level of CRP in the blood is a marker of inflammation. * Patient global assessment of disease activity assessed on a Visual Analog Scale (VAS) ranging from very well to extremely bad was assessed on a 100 point scale. (from 0 to 100) * Physician global assessment of disease activity assessed on a VAS ranging from very low to very high was assessed on 100 point scale * Patient pain scale assessed on a VAS ranging from very well to extremely bad was assessed on 100 point scale * Disability/functional questionnaire (patient completed Heath Assessment Questionnaire Disability Index (HAQ-DI)) A higher response rate is a better outcome. The minimum possible value is 0% and the maximum possible value is 100%

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 0	163 Participants	87 Participants	82 Participants	175 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 4	171 Participants	83 Participants	84 Participants	165 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 8	160 Participants	84 Participants	79 Participants	173 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 12	160 Participants	89 Participants	82 Participants	171 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 24	162 Participants	83 Participants	75 Participants	176 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Period II: Week 30	154 Participants	82 Participants	79 Participants	158 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 42	156 Participants	79 Participants	81 Participants	164 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 54	149 Participants	78 Participants	77 Participants	152 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 66	140 Participants	73 Participants	74 Participants	150 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 76	140 Participants	77 Participants	71 Participants	147 Participants	—
American College of Rheumatology 20 (ACR20) Response Rates From Baseline as a Measure of Efficacy Week 80/EOS	133 Participants	72 Participants	62 Participants	140 Participants	—

SECONDARY outcome

Timeframe: From Week 0 to Week 80

Population: Number of patients at a given time-point with an observed ACR50 score defined as a 50% improvement in tender and swollen joints and at least in 3 out of 5 other indicators from Baseline\_002 (Week 0 of FKB327-002; NCT02260791)

An ACR50 response means that the patient achieved a 50% improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and in at least 3 of the other 5 Core Data Set elements listed below: * Acute phase reactant (C-reactive protein, CRP) A high level of CRP in the blood is a marker of inflammation. * Patient global assessment of disease activity assessed on a Visual Analog Scale (VAS) ranging from very well to extremely bad was assessed on a 100 point scale. (from 0 to 100) * Physician global assessment of disease activity assessed on a VAS ranging from very low to very high was assessed on 100 point scale * Patient pain scale assessed on a VAS ranging from very well to extremely bad was assessed on 100 point scale * Disability/functional questionnaire (patient completed Heath Assessment Questionnaire Disability Index (HAQ-DI)) A higher response rate is a better outcome. The minimum possible value is 0% and the maximum possible value is 100%

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 0	104 Participants	52 Participants	50 Participants	109 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 4	110 Participants	50 Participants	52 Participants	115 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 8	106 Participants	53 Participants	51 Participants	124 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 12	106 Participants	53 Participants	55 Participants	131 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 24	114 Participants	56 Participants	49 Participants	127 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Period II: Week 30	112 Participants	57 Participants	50 Participants	113 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 42	113 Participants	47 Participants	54 Participants	115 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 54	106 Participants	47 Participants	44 Participants	110 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 66	110 Participants	48 Participants	46 Participants	114 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 76	108 Participants	59 Participants	43 Participants	108 Participants	—
American College of Rheumatology 50 (ACR50) Response Rates From Baseline as a Measure of Efficacy Week 80/EOS	102 Participants	47 Participants	43 Participants	112 Participants	—

SECONDARY outcome

Timeframe: From Week 0 to Week 80

Population: Number of patients at a given time-point with an observed ACR70 score defined as a 70% improvement in tender and swollen joints and at least 3 out of 5 other indicators from Baseline\_002 (Week 0 of FKB327-002; NCT02260791)

An ACR70 response means that the patient achieved a 70% improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and in at least 3 of the other 5 Core Data Set elements listed below: * Acute phase reactant (C-reactive protein,CRP) A high level of CRP in the blood is a marker of inflammation. * Patient global assessment of disease activity assessed on a Visual Analog Scale (VAS) ranging from very well to extremely bad was assessed on a 100 point scale. (from 0 to 100) * Physician global assessment of disease activity assessed on a VAS ranging from very low to very high was assessed on 100 point scale * Patient pain scale assessed on a VAS ranging from very well to extremely bad was assessed on 100 point scale * Disability/functional questionnaire (patient completed Heath Assessment Questionnaire Disability Index (HAQ-DI)) A higher response rate is a better outcome. The minimum possible value is 0% and the maximum possible value is 100%

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 80/EOS	64 Participants	27 Participants	25 Participants	69 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 0	45 Participants	23 Participants	23 Participants	56 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 4	54 Participants	30 Participants	29 Participants	54 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 8	61 Participants	29 Participants	26 Participants	72 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 12	59 Participants	28 Participants	29 Participants	69 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 24	65 Participants	30 Participants	25 Participants	80 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Period II: Week 30	67 Participants	33 Participants	28 Participants	74 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 42	72 Participants	27 Participants	26 Participants	74 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 54	69 Participants	29 Participants	19 Participants	69 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 66	69 Participants	29 Participants	25 Participants	73 Participants	—
American College of Rheumatology 70 (ACR70) Response Rates From Baseline as a Measure of Efficacy Week 76	72 Participants	31 Participants	20 Participants	71 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From Week 0 to Week 80

Population: Number of patients who had an assay result of positive Anti-Drug Antibodies at given time-points.

Blood samples for assessment of Anti-Drug antibodies (ADA) were collected prior to dosing (trough samples) at Baseline (Week 0) and at Weeks 12, 24, 30, 54, 76 and 80/EOS. All ADA activity was listed and summarized for each treatment sequence by time point during the overall treatment period as well as by treatment group for each period (Period I and Period II). Descriptive statistics included absolute counts (n) and percentage (%).

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=216 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=108 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=108 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=213 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Last Sampling Day	115 Participants	63 Participants	49 Participants	99 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Week 80/EOS	91 Participants	48 Participants	37 Participants	72 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Week 0	133 Participants	69 Participants	67 Participants	123 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Week 12	107 Participants	60 Participants	54 Participants	101 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Week 24	99 Participants	58 Participants	47 Participants	100 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Period II: Week 30	97 Participants	61 Participants	42 Participants	98 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Week 54	103 Participants	49 Participants	41 Participants	77 Participants	—
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Week 76	90 Participants	49 Participants	39 Participants	74 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From Week 0 to Week 80

Population: Analysis of Serum Concentration Data (ng/mL). Repeated measure of pharmacokinetic(s) (PK) trough concentrations at given time-points.

Blood samples for the quantification of adalimumab concentration in serum were collected prior to dosing (trough samples) at Baseline (Week 0), and at weeks 12, 24 , 30, 54, 76 and 80/EOS.

Outcome measures

Outcome measures
Measure	FKB327-FKB327 n=208 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomized to FKB327 in Period I of study FKB327-003 (F-F).	FKB327-Humira n=105 Participants Period I: This is the treatment arm where subjects had been treated with FKB327 in the preceding study FKB327-002 and were re-randomized to the reference product, Humira, during Period I of study FKB327-003 (F-H).	Humira-FKB327 n=107 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomized to FKB327 during Period I of study FKB327-003 (H-F).	Humira-Humira n=210 Participants Period I: This is the treatment arm where subjects had been treated with the reference product Humira in the preceding study, FKB327-002, and were re-randomized to the reference product Humira during Period I of study FKB327-003 (H-H).	FKB327 Period II From Week 30 all patients were treated with FKB327
Trough Adalimumab Concentration Week 0	6500 ng/mL Standard Deviation 4640	6000 ng/mL Standard Deviation 4520	5170 ng/mL Standard Deviation 3440	5720 ng/mL Standard Deviation 3470	—
Trough Adalimumab Concentration Week 12	6310 ng/mL Standard Deviation 4720	5380 ng/mL Standard Deviation 4150	6180 ng/mL Standard Deviation 3970	6010 ng/mL Standard Deviation 3730	—
Trough Adalimumab Concentration Week 24	5970 ng/mL Standard Deviation 4500	5100 ng/mL Standard Deviation 3990	6320 ng/mL Standard Deviation 4320	5950 ng/mL Standard Deviation 3750	—
Trough Adalimumab Concentration Period II: Week 30	6000 ng/mL Standard Deviation 4450	4790 ng/mL Standard Deviation 4290	5730 ng/mL Standard Deviation 3750	5750 ng/mL Standard Deviation 3680	—
Trough Adalimumab Concentration Week 54	6090 ng/mL Standard Deviation 4620	5830 ng/mL Standard Deviation 4290	5840 ng/mL Standard Deviation 4100	6620 ng/mL Standard Deviation 3920	—
Trough Adalimumab Concentration Week 76	6460 ng/mL Standard Deviation 4140	5900 ng/mL Standard Deviation 4020	6070 ng/mL Standard Deviation 4350	6730 ng/mL Standard Deviation 4080	—
Trough Adalimumab Concentration Week 80	4320 ng/mL Standard Deviation 3130	4000 ng/mL Standard Deviation 3280	4060 ng/mL Standard Deviation 3310	4520 ng/mL Standard Deviation 3100	—

Adverse Events

FKB327

Serious events: 43 serious events

Other events: 125 other events

Deaths: 3 deaths

Humira®

Serious events: 14 serious events

Other events: 46 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	FKB327 n=614 participants at risk FKB327: Solution of FKB327 for subcutaneous injection administered in a dose of 40 mg/0.8mL every 2 weeks for 28 weeks. From week 30 all patients were transferred to receive FKB327 40 mg/0.8 mL every other week presented in an auto-injector (AI) or a pre-filled syringe (PFS). Some patients received continuous FKB327 40 mg every other week by subcutaneous injection for up to 76 weeks.	Humira® n=321 participants at risk Humira®: Solution of Humira® for subcutaneous injection administered in a dose of 40 mg every 2 weeks for 28 weeks. From week 30 to week 76 all patients were transferred to receive FKB327 40 mg/0.8 mL in a pre-filled syringe (PFS) every other week by subcutaneous injection.
Infections and infestations Nasopharyngitis	11.1% 68/614 • Number of events 77 • Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days). The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.	6.9% 22/321 • Number of events 25 • Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days). The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.
Infections and infestations Bronchitis	5.2% 32/614 • Number of events 34 • Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days). The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.	4.4% 14/321 • Number of events 15 • Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days). The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	6.0% 37/614 • Number of events 53 • Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days). The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.	4.7% 15/321 • Number of events 18 • Overall Adverse Events and Serious Adverse Events were collected and monitored up to week 80 for subjects completing the study and 4 weeks after an Early Termination Visit. Period I - from signing of informed consent up to week 30. During this period subjects received either FKB327 or the reference product Humira. Period II: From week 30 to week 76 all subjects received FKB327 hence the maximum duration of FKB327 treatment was about 2.5 times greater compared to the Humira (581 vs 222 days). The overall exposure in patient-years was nearly 4 times greater for FKB327 (673.7) compared to Humira (175.4), due to patients switching from Humira to FKB327 for Period II, which should be taken into account when reviewing the safety results where FKB327 and Humira are directly compared.

Additional Information

Clinical Trial Information

Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch

Phone: 0044 1896 668 173

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator and Sponsor will discuss the preparation of a manuscript for publication in a peer reviewed journal or an abstract for presentation. Either party may undertake the task but both must agree to the strategy before work is started. Each party will allow the other 30 days to comment before any results are submitted for publication or presentation. Authorship should reflect work done by the Investigator an Sponsor, in accordance with recognized principles of scientific collaboration.
Publication restrictions are in place

Restriction type: OTHER