A Study of Tocilizumab (RoActemra) in Tocilizumab-Naive Participants With Rheumatoid Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) and/or Biologic Therapy

Phase 3CompletedNCT02001987

Hoffmann-La Roche139 enrolled

Overview

This two part, multi-center, open-label, single-arm study will evaluate the efficacy and safety of tocilizumab as a monotherapy or in combination with methotrexate or other conventional synthetic disease modifying antirheumatic drugs (csDMARDs) in participants with moderate to severe active rheumatoid arthritis who have an inadequate response or are intolerant to non-biologic csDMARDs and/or biologic therapy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

139

Conditions

Rheumatoid Arthritis

Interventions

TocilizumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants with a diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria and receiving outpatient treatment * Oral corticosteroids (\</= 10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs), and permitted csDMARDs are allowed at a stable dose for at least 4 weeks prior to Baseline * At Screening either CRP \>/=10 mg/L or ESR \>/=20 mm/h and SJC \>/=3 (based on 44 joints) * Inadequate response (IR) to tumor necrosis factor, abatacept and/or non-biological DMARDs Exclusion Criteria: * Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline * Rheumatic autoimmune disease other than rheumatoid arthritis; Secondary Sjögren's syndrome with rheumatoid arthritis is permitted * Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis * Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16 * Prior history of or current inflammatory joint disease other than rheumatoid arthritis * Exposure to tocilizumab at any time prior to Baseline * Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever was longer) of Screening * Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies or any alkylating agents such as chlorambucil, or with total lymphoid irradiation * Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline * Intraarticular or parenteral corticosteroids within 4 weeks prior to Baseline * Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline * History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies * Serious uncontrolled concomitant disease or other significant condition * History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease * Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections * Any infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening * Active tuberculosis requiring treatment within the previous 3 years * Positive for hepatitis B or C * Primary or secondary immunodeficiency disorder * Active cancer, or cancer diagnosed within the previous 10 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised or cured), or breast cancer diagnosed within the previous 20 years * History of alcohol, drug, or chemical abuse within 1 year prior to Screening * Neuropathies or other conditions that might interfere with pain evaluation

Locations (32)

Unnamed facility

Amiens, France

Unnamed facility

Bordeaux, France

Unnamed facility

Brest, France

Unnamed facility

Caen, France

Unnamed facility

Cahors, France

Unnamed facility

Clermont-Ferrand, France

Unnamed facility

Échirolles, France

Unnamed facility

La Source, France

Unnamed facility

Le Mans, France

Unnamed facility

Lille, France

...and 22 more locations

Outcomes

Primary Outcomes

Change From Baseline in Disease Activity Score Based on 28-joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24

The DAS28-ESR was derived from assessments of erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), and Patient Global Assessment of disease activity (PGA) according to 100-millimeter (mm) Visual Analog Scale (VAS). DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in millimeters per hour (mm/h). DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 24 was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Week 24

Secondary Outcomes

Change From Baseline in DAS28-ESR at Weeks 2, 4, 8, 12, 16, 20, and 24

The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-mm VAS. DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Percentage of Participants With DAS28-ESR Low Disease Activity (LDA) and Remission at Week 24

The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-mm VAS. DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. DAS28-ESR score less than or equal to (\</=) 3.2 indicates LDA, DAS28-ESR score greater than (\>) 3.2 indicates moderate to high disease activity, and DAS28-ESR less than (\<) 2.6 indicates remission. Percentage of participants with DAS28-ESR LDA and remission at Week 24 is reported. 95 percent (%) confidence interval (CI) was determined using Clopper-Pearson method.

Time frame: Week 24

Change From Baseline in DAS28-ESR at Week 24 and at Last Assessment

The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-millimeter (mm) VAS. DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Percentage of Participants With DAS28-ESR LDA and Remission at Week 24 and at Last Assessment

The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-mm VAS. DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. DAS28-ESR score \</=3.2 indicates LDA, DAS28-ESR score \>3.2 indicates moderate to high disease activity, and DAS28-ESR \<2.6 indicates remission. Percentage of participants with DAS28-ESR LDA and remission at Week 24 and at last assessment is reported.

Time frame: Week 24, last assessment (up to Week 76)

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response at Week 24

The ACR 20, 50, and 70 responses at any time was defined as greater than or equal to (\>/=) 20%, 50%, and 70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20%, 50%, 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) PGA according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via a Health Assessment Questionnaire-Disability Index (HAQ-DI), and 5) Acute phase reactant (ESR in mm/h or C-Reactive Protein \[CRP\] in milligrams per liter \[mg/L\]). Percentage of participants with ACR 20, 50, and 70 responses at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

Time frame: Baseline, Week 24

Percentage of Participants Achieving ACR20, ACR50, and ACR70 Response at Week 24 and at Last Assessment

The ACR 20, 50, and 70 responses at any time is defined as \>/=20%, 50%, and 70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20%, 50%, 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) PGA according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/L). Percentage of participants with ACR 20, 50, and 70 responses at Week 24 and at last assessment is reported.

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28-ESR at Week 24

The DAS28-ESR-based EULAR response criteria were used to measure individual response as 'Good', 'Moderate', and 'No Response', depending upon DAS28-ESR absolute scores at Week 24 and the DAS28-ESR reduction from Baseline to Week 24. Good Response: change from baseline \>1.2 with DAS28-ESR score \</=3.2; Moderate Response: change from baseline \>1.2 with DAS28-ESR score \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28-ESR score \</=5.1; No Response: change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28-ESR score \>5.1. Percentage of participants with EULAR responses at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

Time frame: Baseline, Week 24

Percentage of Participants With EULAR Response Based on DAS28-ESR at Week 24 and at Last Assessment

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, and 24

SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg per deciliter (dL). Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI \</=3.3 indicates disease remission, \</=11 indicates LDA, \</=26 indicates moderate disease activity, and \>26 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Percentage of Participants With SDAI LDA and Remission at Week 24

SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg/dL. Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI \</=3.3 indicates disease remission, \</=11 indicates LDA, \</=26 indicates moderate disease activity, and \>26 indicates high disease activity. Percentage of participants with SDAI LDA and remission at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

Time frame: Week 24

Change From Baseline in SDAI at Week 24 and at Last Assessment

SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg/dL. Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI \</=3.3 indicates disease remission, \</=11 indicates LDA, \</=26 indicates moderate disease activity, and \>26 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Percentage of Participants With SDAI LDA and Remission at Week 24 and at Last Assessment

SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg/dL. Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI \</=3.3 indicates disease remission, \</=11 indicates LDA, \</=26 indicates moderate disease activity, and \>26 indicates high disease activity. Percentage of participants with SDAI LDA and remission at Week 24 and at last assessment is reported.

Time frame: Week 24, last assessment (up to Week 76)

Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, and 24

CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \</=10 indicates LDA, \</=22 indicates moderate disease activity, and \>22 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Percentage of Participants With CDAI LDA and Remission at Week 24

CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \</=10 indicates LDA, \</=22 indicates moderate disease activity, and \>22 indicates high disease activity. Percentage of participants with CDAI LDA and remission at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

Time frame: Week 24

Change From Baseline in CDAI at Week 24 and at Last Assessment

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Percentage of Participants With CDAI LDA and Remission at Week 24 and at Last Assessment

CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \</=10 indicates LDA, \</=22 indicates moderate disease activity, and \>22 indicates high disease activity. Percentage of participants with CDAI LDA and remission at Week 24 and at last assessment is reported.

Time frame: Week 24, last assessment (up to Week 76)

Change From Baseline in SJC at Weeks 2, 4, 8, 12, 16, 20, and 24

A total of 28 joints were assessed for swelling. The number of swollen joints at could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Change From Baseline in SJC at Week 24 and at Last Assessment

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Change From Baseline in TJC at Weeks 2, 4, 8, 12, 16, 20, and 24

A total of 28 joints were assessed for tenderness. The number of tender joints at could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to any time points was averaged among all participants, where negative changes indicated an improvement in disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Change From Baseline in TJC at Week 24 and at Last Assessment

Time frame: Baseline, Week 24, last assessment (up to Week 76)

Change From Baseline in Physician's Global Assessment of Disease Activity at Weeks 2, 4, 8, 12, 16, 20, and 24

Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity (0 mm=none; 100 mm=very severe). The change from Baseline to any time point was averaged among all participants, where negative change indicated a decrease in physician-assessed disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Change From Baseline in PGA at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity (0 mm=none; 100 mm=very severe). The change from Baseline to any time point was averaged among all participants, where negative change indicated a decrease in participant-assessed disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Change From Baseline in Pain VAS Score at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Participant-assessed pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of pain (0 mm=none; 100 mm=very severe). The change from Baseline to any time point was averaged among all participants, where negative change indicated a decrease in participant-assessed pain.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated questions), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). The changes from Baseline to any time point were averaged among all participants, where negative changes indicated an increase in fatigue.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Remission at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

HAQ-DI assessed 20 items in 8 functional activity domains including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item was scored on a scale of 0 to 3, where 0 represented activities performed without difficulty and 3 represented inability to perform activities alone. The total score (range = 0-3) was calculated as an average of all item scores. Percentage of participants with HAQ-DI remission (HAQ-DI score \<0.5) at each time point is reported.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Percentage of Participants With HAQ-DI Clinically Meaningful Improvement at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

HAQ-DI assessed 20 items in 8 functional activity domains including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item was scored on a scale of 0 to 3, where 0 represented activities performed without difficulty and 3 represented inability to perform activities alone. The total score (range = 0-3) was calculated as an average of all item scores. Percentage of participants with HAQ-DI clinically meaningful improvement (reduction in HAQ-DI score from baseline \>/=0.22) at each time point is reported.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64

Treatment Compliance From Baseline up to Week 24

Treatment compliance from Baseline up to Week 24 was assessed using following formula: (number of actual injection received / number of theoretical injection which should be received at week 24) \* 100.

Time frame: Baseline up to Week 24

Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Score at Weeks 12, 24, 28, 40, 52, and 64

RAID assessed the impact of rheumatoid arthritis on participant's quality of life. It comprised 7 domains: pain, function, fatigue, physical and psychological well-being, sleep disturbance and coping. Each domain was a single question scored from 0 (best) to 10 (worst) on a continuous numerical rating scale (NRS). Each domain also had a specific weight assigned by a participant survey and RAID total score ranged from 0 (best) to 10 (worst). If only 1 domain was missing it was replaced by the mean of the others; otherwise, RAID score was not calculated. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better quality of life.

Time frame: Baseline, Weeks 12, 24, 28, 40, 52, and 64

Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID-3) at Weeks 2, 4, 12, 24, 28, 40, 52, and 64

RAPID-3 is a combined index derived from the Multidimensional Health Assessment Questionnaire that includes physical function score, pain VAS, and PGA VAS. The total RAPID-3 score ranges from 0 to 10 where higher scores represent worse outcomes. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

Time frame: Baseline, Weeks 2, 4, 12, 24, 28, 40, 52, and 64

Number of Participants With Patient Acceptable Symptom State (PASS) Score

Participants were asked: "If you were to remain in the same condition for the next few months as you have been over the last 8 days, would this be 1) acceptable, 2) Inacceptable?" The number of participants who responded "acceptable" or "Inacceptable" at each time point is presented.

Time frame: Baseline, Weeks 24, 52, and last assessment (up to Week 76)

Change From Baseline in Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) Total Score at Weeks 24 and 52

BRAF-MDQ assessed the overall experience and impact of disease related fatigue, using four dimensions (physical fatigue \[4 items\], living with fatigue \[7 items\], cognitive fatigue \[5 items\], and emotional fatigue \[4 items\]). A total fatigue score (range 0 to 70) was obtained by summing the 20 item scores ranging from 0 to 3, except for item 1 (0-10), item 2 (0-7) and item 3 (0-2). Higher scores reflect greater fatigue. If only 1 domain was missing it was replaced by the mean of the others; otherwise, the total score was not calculated. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better quality of life.

Time frame: Baseline, Weeks 24 and 52

Change From Baseline in Bristol Rheumatoid Arthritis Fatigue (BRAF)-NRS Score at Weeks 24 and 52

BRAF-NRS are 3 standardized NRS (range = 0-10) for disease related fatigue domains (severity of fatigue, fatigue effect, and coping with fatigue). Higher values reflect greater problems for severity/level fatigue and effect fatigue NRS, but lower scores reflect greater problems for copped fatigue NRS.

Time frame: Baseline, Weeks 24 and 52

Change From Baseline in Medical Outcome Study (MOS) Sleep Questionnaire Score at Weeks 12, 24, 28, 40, 52, and 64

MOS sleep scale comprised of 6-item with each item score ranged from 0 to 100. The total score was the average of scores sum (range 0-100), with highest values reflecting biggest participant's sleeping problems. If more than 3 items were missing the index was not calculated. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

Time frame: Baseline, Weeks 12, 24, 28, 40, 52, and 64

Change From Baseline in Fluctuations of Disease Activity in Rheumatoid Arthritis (FLARE) Questionnaire Score at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 40, 52, and 64

FLARE is a 13-item questionnaire assessed disease flares between two medical consultations. Each item score ranged from 0 (completely untrue) to 10 (absolutely true) on a 6-step scale. The FLARE questionnaire global score (range = 0-10) is a mean score of 11 of the 13 items \[items 6 ('doses of pain killers or anti-inflammatory medication') and 13 ('need for help') not taken into account\], with the highest score corresponding to the highest disease activity. The global score was computed if at least the scores of 6 items were available. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 40, 52, and 64

Change From Baseline in BioSecure Questionnaire Score at Week 24

The BioSecure questionnaire comprised of 54-item aimed at evaluating the safety competences of participants (for example, participants' self-care safety skills and socio-demographic characteristics, type of information received, quality of life, and coping style data) treated by biologics for inflammatory arthritis and to determine the factors associated with a lower level of competences.

Time frame: Baseline, Week 24

Percentage of Participants With Discontinuations of Corticosteroid Dosage During Core Study Period

Percentage of participants with a discontinuation in corticosteroid dosage during core study period is reported. The discontinuations were categorized as either permanent or temporary. Participants with temporary discontinuation first followed by permanent discontinuation were counted in both categories. Participants who were receiving corticosteroids at Baseline were only included in the analysis.

Time frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks)

Time to Permanent Discontinuation of Corticosteroid Dosage During Core Study Period

Time to permanent discontinuation in corticosteroid dosage during core study period is reported. Participants who permanently discontinued corticosteroids at any time during core study period were only included in the analysis.

Time frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks)

Time to First Temporary Discontinuation of Corticosteroid Dosage During Core Study Period

Time to first temporary discontinuation in corticosteroid dosage during core study period is reported. Participants who temporarily discontinued corticosteroids at any time during core study period were only included in the analysis.

Time frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks)

Percentage of Participants With Change in Corticosteroid Dosage During Core Study Period

Percentage of participants with a change in corticosteroid dosage during core study period compared to Baseline is reported. The change included either an initiation/ increase (\>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (\</=-5mg/day prednisone or equivalent) of corticosteroid dosage.

Time frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks)

Time to Change in Corticosteroid Dosage During Core Study Period

Time to first change in corticosteroid dosage during core study period compared to Baseline is reported. The change included either an initiation/ increase (\>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (\</=-5mg/day prednisone or equivalent) of corticosteroid dosage. Participants with a change in corticosteroid dosage during core study period were only included in the analysis.

Time frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks)

Number of Participants According to Reasons for Change in Corticosteroid Dosage During Core Study Period

Number of participants according to reasons for a change in corticosteroid dosage during core study period compared to Baseline is reported. The change included either an initiation/ increase (\>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (\</=-5mg/day prednisone or equivalent) of corticosteroid dosage. Participants with a change in corticosteroid dosage during core study period were only included in the analysis.

Time frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks)

Percentage of Participants With Discontinuations of Corticosteroid Dosage During Study

Percentage of participants with a discontinuation in corticosteroid dosage during study is reported. The discontinuations were categorized as either permanent or temporary. Participants with temporary discontinuation first followed by permanent discontinuation were counted in both categories. Participants who were receiving corticosteroids at Baseline were only included in the analysis.