Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Participants With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Non-Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs) and/or Anti-tumor Necrosis Factor (Anti-TNF) Therapy

A Study to Observe the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti TNF Therapy.

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01362062

Enrollment

110

Registered

2011-05-27

Start date

2010-10-26

Completion date

2015-01-01

Last updated

2017-08-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Brief summary

This observational study will evaluate the safety, tolerability and efficacy of tocilizumab in participants with moderate to severe RA who have an inadequate response to current non-biologic DMARD and/or anti-TNF therapy. Data will be collected from each participant during tocilizumab therapy and on follow-up for a total of 12 months.

Interventions

DRUGTocilizumab

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Moderate to severe active RA with an inadequate response to existing therapies (DMARDs and/or anti-TNFs) * Considered eligible for tocilizumab therapy by the treating physician as per routine clinical practice

Exclusion criteria

* Pregnant or breastfeeding females * Immunization with live/attenuated vaccine within 4 weeks prior to baseline * Participants with clinically significant raised liver enzyme, abnormal lipid profile, platelet count, hemoglobin, white blood cell and neutrophil count * History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies * Participants with active tuberculosis (TB). Participants with latent TB should be treated with standard anti-mycobacterial therapy before initiating tocilizumab and have a negative chest x ray for active TB at enrolment * History of diverticulitis, chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations then the benefit risk ratio should be considered by treating physician * Know active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infection * History of or currently active primary or secondary immunodeficiency or known human immunodeficiency virus (HIV) positive status * Any other condition which puts the participant to undue risk for tocilizumab therapy as per local prescribing information or Investigator's judgement

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)	Up to 12 months	An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal product. An AE is considered as an SAE if it fulfills one of the following criteria: a) fatal or life-threatening, b) requires in-patient hospitalization or prolongation of existing hospitalization, c) results in a persistent or significant disability, d) results in a congenital abnormality/birth defect, e) is medically significant. AEs included serious as well as non-serious AEs.

Secondary

Measure	Time frame	Description
Time Required to Achieve Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units)	Up to 12 months	DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\√(TJC) + 0.28\√(SJC) + 0.70\log natural (ESR) + 0.014\global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement. Time taken to achieve clinically meaningful improvement in DAS28 was reported.
Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\√(TJC) + 0.28\√(SJC) + 0.70\log natural (ESR) + 0.014\global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low Disease Activity is defined as DAS28 value of \<3.2 Units at the time of assessment.
Time Required to Achieve Low Disease Activity (DAS28 <3.2 Units)	Up to 12 months	DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\√(TJC) + 0.28\√(SJC) + 0.70\log natural (ESR) + 0.014\global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low disease activity is defined as decrease in DAS28 to a value \<3.2 Units at the time of assessment. Time taken to achieve low disease activity was reported.
Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\√(TJC) + 0.28\√(SJC) + 0.70\log natural (ESR) + 0.014\global assessment of disease activity (100 mm VAS). Remission is defined as DAS28 value of \<2.6 units at the time of assessment.
Time Taken to Achieve Remission (DAS28 <2.6 Units)	Up to 12 months	DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\√(TJC) + 0.28\√(SJC) + 0.70\log natural (ESR) + 0.014\global assessment of disease activity (100 mm VAS). Remission is defined as DAS28 value of \<2.6 units at the time of assessment. Time taken to achieve remission is reported.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 42), Visit 13 (Week 44)	ACR20/ACR50/ACR70/ACR 90 response: greater than or equal to (≥) 20%/50%/70%/90% improvement in tender and swollen joint counts and 20%/50%/70%/90% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) Participant assessment of disease activity, 3) Participant assessment of pain (VAS), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) ESR at each visit.
Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	DAS28 was calculated from the tender joint count (TJC) of 28 joints, swollen joint count (SJC) of 28 joints, erythrocyte sedimentation rate (ESR) (in millimeters \[mm\]/hour), and the participant's global assessment of disease activity (100 mm visual analog scale \[VAS\]: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\square root (√) of TJC + 0.28\√(SJC) + 0.70\log natural (ESR) + 0.014\global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement.
Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	—
Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, and is described as maximum disease activity (maximum arthritis disease activity). A negative change from baseline indicated improvement.
Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, and is described as maximum disease activity (maximum arthritis disease activity).
Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	The participant assessed their pain on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm, and is described as unbearable pain. A negative change indicated improvement.
Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	HAQ-DI is a self-completed patient questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The HAQ-DI is the sum of the scores from all domains and ranged from 0 (best) to 24 (worst). A negative change from baseline indicated improvement.
Change From Baseline (CFB) in ESR Values at Every Visit	Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)	—

Countries

India

Participant flow

Participants by arm

Arm	Count
RA Cohort (Prospective) Participants with active RA who had an inadequate clinical response to current non-biologic DMARD and/or anti-TNF therapy being treated with tocilizumab according to the routine clinical practice and in line with prescribing information were observed prospectively for a total duration of 12 months.	48
RA Cohort (Retrospective) Participants with active RA who had an inadequate clinical response to current non-biologic DMARD and/or anti-TNF therapy being treated with tocilizumab according to the routine clinical practice and in line with prescribing information were observed retrospectively for a total duration of 12 months.	62
Total	110

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Detected with Spondylo-arthritis	1
Overall Study	Had significant improvement	9
Overall Study	Lost to Follow-up	11
Overall Study	Non-compliant participant	2
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	RA Cohort (Prospective)	RA Cohort (Retrospective)	Total
Age, Continuous	51.19 years STANDARD_DEVIATION 10.44	50.39 years STANDARD_DEVIATION 12.56	50.74 years STANDARD_DEVIATION 11.64
Sex: Female, Male Female	40 Participants	54 Participants	94 Participants
Sex: Female, Male Male	8 Participants	8 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	35 / 110
serious Total, serious adverse events	8 / 110

Outcome results

Primary

Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)

An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal product. An AE is considered as an SAE if it fulfills one of the following criteria: a) fatal or life-threatening, b) requires in-patient hospitalization or prolongation of existing hospitalization, c) results in a persistent or significant disability, d) results in a congenital abnormality/birth defect, e) is medically significant. AEs included serious as well as non-serious AEs.

Time frame: Up to 12 months

Population: Safety analysis population: Included all participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (NUMBER)
RA Cohort (Prospective + Retrospective)	Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)	AEs	31.8 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)	SAEs	7.2 percentage of participants

Secondary

Change From Baseline (CFB) in ESR Values at Every Visit

Time frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome.

Arm	Measure	Group	Value (MEAN)	Dispersion
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 3	-34.03 mm/hour	Standard Deviation 30.87
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 4	-39.63 mm/hour	Standard Deviation 31.4
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 5	-38.03 mm/hour	Standard Deviation 32.07
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 6	-38.71 mm/hour	Standard Deviation 30.26
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 7	-41.66 mm/hour	Standard Deviation 33.23
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 8	-39.07 mm/hour	Standard Deviation 34.08
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 9	-33.26 mm/hour	Standard Deviation 37.61
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 10	-35.89 mm/hour	Standard Deviation 35.81
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 11	-37.52 mm/hour	Standard Deviation 32.42
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 12	-40.37 mm/hour	Standard Deviation 35.38
RA Cohort (Prospective + Retrospective)	Change From Baseline (CFB) in ESR Values at Every Visit	CFB at Visit 13	-38.70 mm/hour	Standard Deviation 35.32

Comparison: Statistical analysis for CFB at Visit 3.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 4.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 5.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 6.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 7.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 8.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 9.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 10.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 11.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 12.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 13.p-value: =0.001Paired t-test

Secondary

Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome.

Arm	Measure	Group	Value (MEAN)	Dispersion
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 3	-12.34 milligrams per deciliter (mg/dL)	Standard Deviation 14.48
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 4	-12.82 milligrams per deciliter (mg/dL)	Standard Deviation 16.24
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 5	-13.77 milligrams per deciliter (mg/dL)	Standard Deviation 15.26
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 6	-12.15 milligrams per deciliter (mg/dL)	Standard Deviation 18.24
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 7	-16.51 milligrams per deciliter (mg/dL)	Standard Deviation 15.57
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 8	-13.92 milligrams per deciliter (mg/dL)	Standard Deviation 18.98
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 9	-12.79 milligrams per deciliter (mg/dL)	Standard Deviation 19.17
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 10	-13.24 milligrams per deciliter (mg/dL)	Standard Deviation 18.53
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 11	-14.74 milligrams per deciliter (mg/dL)	Standard Deviation 14.7
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 12	-16.65 milligrams per deciliter (mg/dL)	Standard Deviation 15.17
RA Cohort (Prospective + Retrospective)	Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit	CFB at Visit 13	-15.69 milligrams per deciliter (mg/dL)	Standard Deviation 14.97

Comparison: Statistical analysis for CFB at Visit 3.p-value: =0.003Paired t-test

Comparison: Statistical analysis for CFB at Visit 4.p-value: =0.005Paired t-test

Comparison: Statistical analysis for CFB at Visit 5.p-value: =0.002Paired t-test

Comparison: Statistical analysis for CFB at Visit 6.p-value: =0.014Paired t-test

Comparison: Statistical analysis for CFB at Visit 7.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 8.p-value: =0.008Paired t-test

Comparison: Statistical analysis for CFB at Visit 9.p-value: =0.014Paired t-test

Comparison: Statistical analysis for CFB at Visit 10.p-value: =0.009Paired t-test

Comparison: Statistical analysis for CFB at Visit 11.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 12.p-value: =0.001Paired t-test

Comparison: Statistical analysis for CFB at Visit 13.p-value: =0.001Paired t-test

Secondary

Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit

HAQ-DI is a self-completed patient questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The HAQ-DI is the sum of the scores from all domains and ranged from 0 (best) to 24 (worst). A negative change from baseline indicated improvement.

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome.

Arm	Measure	Group	Value (MEAN)	Dispersion
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 3	-02.40 units on scale	Standard Deviation 9.08
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 4	-02.21 units on scale	Standard Deviation 10.2
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 5	-03.79 units on scale	Standard Deviation 13.43
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 6	-03.85 units on scale	Standard Deviation 12.94
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 7	-04.05 units on scale	Standard Deviation 10.67
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 8	-03.92 units on scale	Standard Deviation 11.16
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 9	-03.90 units on scale	Standard Deviation 11.68
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 10	-03.11 units on scale	Standard Deviation 10.76
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 11	-04.28 units on scale	Standard Deviation 12.4
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 12	-04.35 units on scale	Standard Deviation 12.38
RA Cohort (Prospective + Retrospective)	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit	CFB at Visit 13	-04.39 units on scale	Standard Deviation 12.37

Comparison: Statistical analysis for CFB at Visit 3.p-value: =0.064Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 4.p-value: =0.104Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 5.p-value: =0.052Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 6.p-value: =0.043Wilcoxon sign rank test

Comparison: Statistical analysis for CFB of Visit 7.p-value: =0.015Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 8.p-value: =0.023Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 9.p-value: =0.028Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 10.p-value: =0.048Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 11.p-value: =0.025Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 12.p-value: =0.023Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 13.p-value: =0.022Wilcoxon sign rank test

Secondary

Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit

The participant assessed their pain on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm, and is described as unbearable pain. A negative change indicated improvement.

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome.

Arm	Measure	Group	Value (MEAN)	Dispersion
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 9	-31.10 millimeters	Standard Deviation 28.21
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 3	-13.66 millimeters	Standard Deviation 19.43
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 4	-20.93 millimeters	Standard Deviation 22.23
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 5	-21.14 millimeters	Standard Deviation 26.46
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 6	-26.34 millimeters	Standard Deviation 27.32
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 7	-29.32 millimeters	Standard Deviation 27.19
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 8	-29.75 millimeters	Standard Deviation 27.97
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 10	-30.17 millimeters	Standard Deviation 27.83
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 11	-33.88 millimeters	Standard Deviation 30.19
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 12	-33.71 millimeters	Standard Deviation 28.25
RA Cohort (Prospective + Retrospective)	Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 13	-33.63 millimeters	Standard Deviation 28.33

Comparison: Statistical analysis for CFB at Visit 3.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 4.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 5.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 6.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 7.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 8.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 9.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 10.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 11.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 12.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 13.p-value: =0.001Wilcoxon sign rank test

Secondary

Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit

The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, and is described as maximum disease activity (maximum arthritis disease activity). A negative change from baseline indicated improvement.

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome.

Arm	Measure	Group	Value (MEAN)	Dispersion
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 3	-11.34 millimeters	Standard Deviation 21.97
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 4	-18.67 millimeters	Standard Deviation 26.29
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 5	-17.86 millimeters	Standard Deviation 33.62
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 6	-24.51 millimeters	Standard Deviation 35.4
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 7	-25.90 millimeters	Standard Deviation 36.66
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 8	-27.20 millimeters	Standard Deviation 37.13
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 9	-28.17 millimeters	Standard Deviation 37.5
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 10	-27.25 millimeters	Standard Deviation 37.07
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 11	-30.71 millimeters	Standard Deviation 39.16
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 12	-30.42 millimeters	Standard Deviation 38.13
RA Cohort (Prospective + Retrospective)	Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 13	-30.34 millimeters	Standard Deviation 37.86

Comparison: Statistical analysis for CFB at Visit 7.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 3.p-value: =0.002Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 4.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 5.p-value: =0.002Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 6.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 8.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 9.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 10.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 11.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 12.p-value: =0.001Wilcoxon sign rank test

Comparison: Statistical analysis for CFB at Visit 13.p-value: =0.001Wilcoxon sign rank test

Secondary

Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit

DAS28 was calculated from the tender joint count (TJC) of 28 joints, swollen joint count (SJC) of 28 joints, erythrocyte sedimentation rate (ESR) (in millimeters \[mm\]/hour), and the participant's global assessment of disease activity (100 mm visual analog scale \[VAS\]: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*square root (√) of TJC + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement.

Time frame: Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44)

Population: Efficacy analysis population included participants who were observed prospectively in this study. Number of participants analyzed = number of participants evaluable for this outcome and n = number of participants evaluable at the specified time point.

Arm	Measure	Group	Value (NUMBER)
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 3 (n=38)	55.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 4 (n=37)	73.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 5 (n=37)	81.1 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 6 (n=36)	80.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 7 (n=39)	84.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 8 (n=21)	90.5 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 9 (n=20)	85.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 10 (n=18)	88.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 11 (n=23)	87.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 12 (n=20)	95.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Visit 13 (n=17)	94.1 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit	Overall (n=43)	97.7 percentage of participants

Secondary

Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit

ACR20/ACR50/ACR70/ACR 90 response: greater than or equal to (≥) 20%/50%/70%/90% improvement in tender and swollen joint counts and 20%/50%/70%/90% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) Participant assessment of disease activity, 3) Participant assessment of pain (VAS), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) ESR at each visit.

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome and n = number of participants evaluable at the specified time point.

Arm	Measure	Group	Value (NUMBER)
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 3: ACR 20 response (n=29)	86.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 3: ACR 50 response (n=29)	10.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 3: ACR 70 response (n=29)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 3: ACR 90 response (n=29)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 4: ACR 20 response (n=33)	75.8 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 4: ACR 50 response (n=33)	18.2 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 4: ACR 70 response (n=33)	3.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 4: ACR 90 response (n=33)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 5: ACR 20 response (n=28)	53.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 5: ACR 50 response (n=28)	28.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 5: ACR 70 response (n=28)	14.2 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 5: ACR 90 response (n=28)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 6: ACR 20 response (n=31)	41.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 6: ACR 50 response (n=31)	35.5 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 6: ACR 70 response (n=31)	22.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 6: ACR 90 response (n=31)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 7: ACR 20 response (n=30)	36.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 7: ACR 50 response (n=30)	26.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 7: ACR 70 response (n=30)	30.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 7: ACR 90 response (n=30)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 8: ACR 20 response (n=17)	52.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 8: ACR 50 response (n=17)	23.5 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 8: ACR 70 response (n=17)	17.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 8: ACR 90 response (n=17)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 9: ACR 20 response (n=16)	18.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 9: ACR 50 response (n=16)	56.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 9: ACR 70 response (n=16)	25.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 9: ACR 90 response (n=16)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 10: ACR 20 response (n=12)	33.4 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 10: ACR 50 response (n=12)	33.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 10: ACR 70 response (n=12)	33.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 10: ACR 90 response (n=12)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 11: ACR 20 response (n=17)	29.4 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 11: ACR 50 response (n=17)	23.5 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 11: ACR 70 response (n=17)	47.1 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 11: ACR 90 response (n=17)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 12: ACR 20 response (n=15)	13.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 12: ACR 50 response (n=15)	46.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 12: ACR 70 response (n=15)	40.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 12: ACR 90 response (n=15)	0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 13: ACR 20 response (n=11)	9.1 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 13: ACR 50 response (n=11)	27.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 13: ACR 70 response (n=11)	63.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit	Visit 13: ACR 90 response (n=11)	0 percentage of participants

Secondary

Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit

DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70\*log natural (ESR) + 0.014\*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low Disease Activity is defined as DAS28 value of \<3.2 Units at the time of assessment.

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome and n = number of participants evaluable at the specified time point.

Arm	Measure	Group	Value (NUMBER)
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 3 (n=38)	15.8 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 4 (n=37)	27.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 5 (n=37)	29.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 6 (n=36)	44.4 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 7 (n=39)	46.2 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 8 (n=21)	42.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 9 (n=20)	45.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 10 (n=18)	50.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 11 (n=23)	60.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 12 (n=20)	70.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Visit 13 (n=17)	64.7 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit	Overall (n=43)	74.4 percentage of participants

Secondary

Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome and n = number of participants evaluable at the specified time point.

Arm	Measure	Group	Value (NUMBER)
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 3 (n=38)	5.3 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 4 (n=37)	10.8 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 5 (n=37)	16.2 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 6 (n=36)	30.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 7 (n=39)	35.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 8 (n=21)	28.6 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 9 (n=20)	35.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 10 (n=18)	38.9 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 11 (n=23)	52.2 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 12 (n=20)	55.0 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Visit 13 (n=17)	58.8 percentage of participants
RA Cohort (Prospective + Retrospective)	Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit	Overall (n=43)	60.5 percentage of participants

Secondary

Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit

The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, and is described as maximum disease activity (maximum arthritis disease activity).

Population: Efficacy analysis population. Number of participants analyzed = number of participants evaluable for this outcome.

Arm	Measure	Group	Value (MEAN)	Dispersion
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 3	-17.78 millimeters	Standard Deviation 19.72
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 4	-23.56 millimeters	Standard Deviation 24.64
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 5	-23.85 millimeters	Standard Deviation 33
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 6	-29.06 millimeters	Standard Deviation 33.91
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 7	-27.22 millimeters	Standard Deviation 34.9
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 8	-29.00 millimeters	Standard Deviation 35.51
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 9	-29.86 millimeters	Standard Deviation 36.32
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 10	-28.68 millimeters	Standard Deviation 35.95
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 11	-32.51 millimeters	Standard Deviation 37.57
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 12	-32.10 millimeters	Standard Deviation 36.58
RA Cohort (Prospective + Retrospective)	Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit	CFB at Visit 13	-32.64 millimeters	Standard Deviation 36.93