A Study of CNTO 136 (Sirukumab) Administered Subcutaneously in Japanese Patients With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine

A Multicenter, Randomized, Double-blind, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously as Monotherapy, in Japanese Subjects With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01689532

Enrollment

122

Registered

2012-09-21

Start date

2012-11-30

Completion date

2015-03-31

Last updated

2016-10-27

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

Conditions

Arthritis, Rheumatoid

Keywords

Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine, Sirukumab, Human Anti-IL-6 Monoclonal Antibody

Brief summary

The purpose of this study is to evaluate the safety and efficacy of sirukumab as a single therapy in Japanese patients with moderately to severely active rheumatoid arthritis (RA) who have not responded to treatment with methotrexate (MTX) or sulfasalazine (SSZ).

Detailed description

This is a randomized (patients will be assigned to treatment by chance), double-blind (study personnel and patients will not know what treatments are being given), multicenter study. The expected duration of the study is 68 weeks. This will include 52 weeks of treatment with study agent with dosing every 2 weeks and 16 weeks of safety follow-up after the last dose. Disease-modifying antirheumatic drugs (DMARDs), including MTX and SSZ, are not permitted from 4 weeks before the first dosing with study agent until Week 24. The use of DMARDs is discouraged at or any time after Week 24; however, patients who have less than 20% improvement from baseline in both swollen and tender joint counts at Week 24 will be allowed to take DMARDs. At or any time after Week 16, the initiation and/or adjustment of oral corticosteroids will be allowed for patients who have less than 20% improvement from baseline in both swollen and tender joint counts at Week 16.

Interventions

DRUGSirukumab 100 mg

Sirukumab 100 mg subcutaneous (SC) injection, at Weeks 0, 2, and every 2 weeks through Week 52.

DRUGSirukumab 50 mg

Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52.

DRUGPlacebo

Between sirukumab injections, placebo SC at Weeks 2, 6, and every 4 weeks through Week 52.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* Be a Japanese man or woman with a diagnosis of rheumatoid arthritis (RA), according to the revised 1987 criteria of the American Rheumatism Association, for at least 3 months before screening * Has moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline * Has been unresponsive to adequate treatment with methotrexate (MTX), sulfasalazine (SSZ), or combination of MTX or SSZ with other disease-modifying antirheumatic drugs (DMARDs) at screening due to lack of benefit after at least 12 weeks of marketed dose of MTX or SSZ, as assessed by the treating physician. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or overall disease activity * If using oral corticosteroids, must be on a stable dose equivalent to \<=10 mg/day of prednisolone for at least 2 weeks prior to first dosing with study agent. If currently not using corticosteroids, the patient must not have received oral corticosteroids (by mouth) for at least 2 weeks prior to first dosing with study agent * If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics (pain relievers) for RA, must be on a stable dose for at least 2 weeks prior to first dosing with study agent

Exclusion criteria

* Has a history of intolerance to at least 2 or inadequate response to at least one anti-tumor necrosis factor-alpha (anti-TNF-alpha) agent after 3 months of therapy; has received anti-TNF-alpha (eg, infliximab, golimumab, adalimumab, or etanercept) within 3 months of first study agent dosing * Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy; has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent dosing or has evidence during screening of abnormally low B-cell level caused by previous B-cell depletion therapy; has used any other biologic therapy for the treatment of RA within 3 months of first study agent dosing; has a history of sirukumab use * Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent dosing * Has received leflunomide within 24 months before first study agent dosing and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. Drug elimination procedure must be completed prior to obtaining informed consent * Has a history of cyclophosphamide or cytotoxic agent use; has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of first study agent dosing; has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half-lives, whichever is longer, before first study agent dosing

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events (TEAE)	Baseline upto Week 68	A TEAE was defined as an event that occurred in the treatment period during which it emerged (that is \[i.e.\] started or worsened in severity, relation, or other attribute), and even if the event continued to be present.

Secondary

Measure	Time frame	Description
Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Response	At Weeks 16 and 24	The ACR 50 Response is defined as \>=50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and serum CRP.
Percentage of Participants Achieving American College of Rheumatology (ACR) 70 Response	At Weeks 16 and 24	The ACR 70 Response is defined as \>=70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and CRP.
Percentage of Participants Achieving American College of Rheumatology (ACR) 90 Response	At Weeks 16 and 24	The ACR 90 Response is defined as \>=90 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=90 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and CRP.
Percent Change From Baseline in Number of Swollen Joints at Weeks 16 and 24	Baseline, Weeks 16 and 24	Sixty six (66) joints were assessed for swelling by investigator to determine the number of joints that were considered swollen. A negative change from baseline in swollen joint count indicates improvement.
Percent Change From Baseline in Number of Tender Joints at Weeks 16 and 24	Baseline, Weeks 16 and 24	Sixty eight (68) joints were assessed for tenderness to determine the number of joints that were considered tender. A negative change from baseline in the tender joint count indicates improvement.
Percent Change From Baseline in Patient's Assessment of Pain at Weeks 16 and 24	Baseline, Weeks 16 and 24	Participants assessed their average pain during the past week on a visual analogue scale (VAS). The scale ranged from 0 (no pain) to 10 (the worst possible pain).
Percent Change From Baseline in Patient's Global Assessment of Disease Activity at Weeks 16 and 24	Baseline, Weeks 16 and 24	Participants rated their disease activity using the Visual Analog Scale (VAS) on a scale of 0 (very well) to 10 (very poor).
Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Weeks 16 and 24	Baseline, Weeks 16 and 24	Physician's Global Assessment of Disease Activity was assessed using the VAS on a scale of 0 (no arthritis activity) to 10 (extremely active arthritis).
Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 16 and 24	Baseline, Weeks 16 and 24	The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Here, 'n' signifies those participants who were evaluable for the specific timepoint.
Percent Change From Baseline in C-Reactive Protein (CRP) at Weeks 16 and 24	Baseline, Weeks 16 and 24	Serum CRP is a marker of systemic inflammation. A negative percent change from baseline in CRP represents improvement.
Percentage of Participants Who Achieved Major Clinical Response at Week 52	Week 52	Major clinical response is achieving ACR 70 for 6 continuous months. The ACR 70 Response is defined as \>=70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS, (The scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and CRP. Achievement of major clinical response reflects an enhanced level of therapeutic efficacy and sustained reduction of signs and symptoms of rheumatoid arthritis (RA).
Percentage of Participants With Disease Activity Index Score 28 (CRP) Response at Weeks 16 and 24	At Weeks 16 and 24	The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. Good responders: improvement from baseline greater than (\>) 1.2 with DAS28 less than or equal to (\<=) 3.2; moderate responders: improvement from baseline \>1.2 with DAS28 \>3.2 to \<=5.1 or improvement from baseline \>0.6 to \<=1.2 with DAS28 \<=5.1; non-responders: improvement from baseline \<=0.6 or improvement from baseline \>0.6 and \<=1.2 with DAS28 \>5.1.
Percentage of Participants Achieving DAS28 (CRP) Remission at Week 24	At Week 24	The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. DAS28 (CRP) remission is defined as a DAS28 (CRP) value of less than (\<) 2.6 at any study visit.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response	At Weeks 16 and 24	The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
Percentage of Participants With Simplified Disease Activity Index (SDAI) Based ACR/European League Against Rheumatism (EULAR) Remission at Weeks 16, 24 and 52	At Weeks 16, 24 and 52	The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity on VAS, physician's global assessments of disease activity on VAS, and CRP. SDAI-based ACR/EULAR remission is defined as a SDAI value of \<=3.3 at the visit.
Percentage of Participants With Boolean Based ACR/EULAR Remission at Weeks 16, 24 and 52	At Weeks 16, 24 and 52	The Boolean based ACR/EULAR remission is achieved if all of the following 4 criteria at that visit are met: tender joint count (68 joints) \<=1; swollen joint count (66 joints) \<=1; CRP \<=1 milligram per deciliter (mg/dL); and patient's global assessment of disease activity on visual analog scale (VAS) \<=1 on a 0 to 10 scale.
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Weeks 16 and 24	Baseline, Weeks 16 and 24	The CDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score range is 0-76. Score interpretation: Remission \<=2.8; Low Disease Activity CDAI \> 2.8 and \<=10; Moderate Disease Activity CDAI \>10 and \<=22; High Disease Activity CDAI \> 22.
Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Weeks 16 and 24	Baseline, Weeks 16 and 24	The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, physician's global assessments of disease activity, and CRP. The total score range is 0-86. Score interpretation: Remission SDAI \<=3.3; Low Disease Activity SDAI \>3.3 and \<=11; Moderate Disease Activity SDAI \>11 and \<=26; High Disease Activity SDAI \>26.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 16 and 24	Baseline, at Week 16 and 24	The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Percentage of Participants Achieving HAQ-DI Response at Weeks 16 and 24	At Weeks 16 and 24	The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). HAQ-DI response was defined as change of \> -0.22 from baseline in HAQ-DI score.
Percentage of Participants Maintaining HAQ-DI Response	Baseline upto Week 52	The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). HAQ-DI responders who maintain a change from baseline of \> -0.22 in HAQ-DI score.
Area Under Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52	Baseline, Weeks 24 and 52	HAQ-DI consisted of 20-question in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. AUC of change from baseline in HAQ-DI score is the AUC of change from baseline in HAQ-DI score versus the time. AUC was calculated based on the measurement (i.e., observed HAQ-DI score change from baseline) at scheduled visits using the trapezoidal rule. Functional status was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time.
Change From Baseline in Duration of Morning Stiffness at Weeks 16 and 24	Baseline, Weeks 16 and 24	Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported; If stiffness persisted the entire day, 1440 minutes was recorded). Negative values for this outcome measure represent improvement, i.e. shortening of duration of morning stiffness.
Change From Baseline in Mental Component Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 16, 24 and 52	Baseline, Weeks 16, 24 and 52	The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary mental component score (MCS) is derived. Scales contributing most to the scoring of the SF-36 MCS include the VT, SF, RE and MH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary MCS score is also scaled from 0 to 100 with higher scores indicating better health.
Change From Baseline in Physical Component Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 16, 24 and 52	Baseline, Weeks 16, 24 and 52	The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary physical component score (PCS) is derived. Scales contributing most to the scoring of the SF-36 PCS include the PF, RP, BP and GH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary PCS score is also scaled from 0 to 100 with higher scores indicating better health.
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Visual Analog Scale (VAS) Score at Weeks 16, 24 and 52	Baseline, Weeks 16, 24 and 52	The EQ-5D VAS records the participant's self-rated health on a vertical, VAS, with 0 representing the worst imaginable health state and 100 representing the best imaginable health state. The EQ VAS is used as a quantitative measure of health outcome as judged by the individual participant.
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score at Weeks 16, 24 and 52	Baseline, Weeks 16, 24 and 52	Change from Baseline to end point in Euro Quality of life (Qol)-5 Dimension Questionnaire (EQ-5D). A higher score indicates an improvement in health in the Health Status Index. The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating full health and 0 representing dead.
Change From Baseline in DAS28 (CRP) Score at Weeks 16 and 24	Baseline, Weeks 16 and 24	The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.

Countries

Japan

Participant flow

Pre-assignment details

Of the 180 participants who signed informed consent of this study, 122 participants (61 participants in each treatment group) were randomized and treated during the study.

Participants by arm

Arm	Count
Sirukumab 50 Milligram (mg) Participants received sirukumab 50 milligram (mg) subcutaneous (SC) at Weeks 0, 4, and every 4 weeks (q4w) through Week 52. Between sirukumab injections, participants received placebo SC at Weeks 2, 6, and q4w through Week 52.	61
Sirukumab 100 mg Participants received Sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks (q2w) through Week 52.	61
Total	122

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	9	5
Overall Study	Lack of Efficacy	2	2
Overall Study	Physician Decision	2	0
Overall Study	Withdrawal by Subject	1	2

Baseline characteristics

Characteristic	Sirukumab 50 Milligram (mg)	Sirukumab 100 mg	Total
Age, Continuous	55.4 years STANDARD_DEVIATION 10.7	54.7 years STANDARD_DEVIATION 12.16	55.1 years STANDARD_DEVIATION 11.41
Region of Enrollment JAPAN	61 participants	61 participants	122 participants
Sex: Female, Male Female	47 Participants	43 Participants	90 Participants
Sex: Female, Male Male	14 Participants	18 Participants	32 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	48 / 61	51 / 61
serious Total, serious adverse events	4 / 61	5 / 61

Outcome results

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAE)

A TEAE was defined as an event that occurred in the treatment period during which it emerged (that is \[i.e.\] started or worsened in severity, relation, or other attribute), and even if the event continued to be present.

Time frame: Baseline upto Week 68

Population: Safety analyses set included all participants who received at least 1 (partial or complete) dose of the study drug.

Arm	Measure	Value (NUMBER)
Sirukumab 50 Milligram (mg)	Number of Participants With Treatment Emergent Adverse Events (TEAE)	56 participants
Sirukumab 100 mg	Number of Participants With Treatment Emergent Adverse Events (TEAE)	58 participants

Secondary

Area Under Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52

HAQ-DI consisted of 20-question in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. AUC of change from baseline in HAQ-DI score is the AUC of change from baseline in HAQ-DI score versus the time. AUC was calculated based on the measurement (i.e., observed HAQ-DI score change from baseline) at scheduled visits using the trapezoidal rule. Functional status was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time.

Time frame: Baseline, Weeks 24 and 52