Musculoskeletal Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Immune System Diseases

Arthritis

Necrosis

Arthritis, Rheumatoid

Rheumatic Diseases

Joint Diseases

Collagen Diseases

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All Drugs and Chemicals

Anti-Inflammatory Agents

Micronutrients

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Methotrexate

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Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

Participants will receive a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.

Participants will receive a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.

Tocilizumab

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study. The study protocol does not specify any particular therapy.

DMARDs

Stable oral corticosteroids doses (≤10 mg/day prednisone or equivalent) are allowed. The study protocol does not specify any additional detail on types of oral corticosteroids.

Oral Corticosteroids

Methotrexate per investigator's discretion.

Clinical Trials

This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52 weeks.

A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent

Open-Label, Phase IIIb Study to Evaluate the Efficacy and Safety of Subcutaneous (SC) Tocilizumab Monotherapy or Combination Therapy With Methotrexate (MTX) or Other Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Patients With Active Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-Tumour Necrosis Factor (Anti-TNF) Biologic Agent

DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour \[mm/hour\]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale \[VAS\] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR greater than or equal to (≥) 2.6 to less than or equal to (≤) 3.2 implied low disease activity, greater than (\>) 3.2 to ≤5.1 implied moderate disease activity, \>5.1 implied high/severe disease, and less than (\<) 2.6 implied clinical remission.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, \>3.2 to ≤5.1 implied moderate disease activity, \>5.1 implied high/severe disease, and \<2.6 implied clinical remission.

A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either C-reactive protein \[CRP\] or ESR).

A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR).

A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[VAS: 0 mm=no disease activity to 100 mm=maximum disease activity\]; 3) Patient's Assessment of Pain \[VAS: 0 mm=no pain to 100 mm=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do\] and 5) an acute-phase reactant (either CRP or ESR).

DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline \>0.6 to ≤1.2 with a DAS28 score \>5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.

The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI ≤3.3 indicates clinical remission, \>3.3 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity.

The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI ≤2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high (or severe) disease activity.

Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68. A reduction in number of tender joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).

Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of tender joints compared to baseline indicates improvement.

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66. A reduction in number of swollen joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).

Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of swollen joints compared to baseline indicates improvement.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR \<2.6 implied clinical remission.

Results are reported for number of participants who had non-biologic DMARD/corticosteroid dose reductions and/or discontinuation by reasons for dose reductions or discontinuation (safety reasons, discomfort, lack of efficacy, other reasons, and unknown reasons). Participants may be included under more than one reason.

Methotrexate adherence was determined from responses to the question 'Over the last 3 months you were prescribed 12 doses of methotrexate, how many (approximately) have you taken?' Adherence (%) was calculated as: (Approximate number of doses taken/12)\*100.

Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.

This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.

The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.

The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater 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-F score for a total possible score of 0 (worse score) to 52 (better score).

A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.

Hoffmann-La Roche

Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.

Tocilizumab Monotherapy

Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.

Tocilizumab in Combination With Methotrexate or Other DMARDs

Total

Age, Continuous

Sex: Female, Male

FAS population included all participants who received at least one dose of SC tocilizumab.

Medical Communications

Baseline

Change at Week 2

FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2

Change From Baseline in DAS28-ESR at Week 4

Change From Baseline in DAS28-ESR at Week 8

Change From Baseline in DAS28-ESR at Week 12

Change From Baseline in DAS28-ESR at Week 16

Change From Baseline in DAS28-ESR at Week 20

Change From Baseline in DAS28-ESR at Week 24

Change From Baseline in DAS28-ESR at Week 28

Change From Baseline in DAS28-ESR at Week 32

Change From Baseline in DAS28-ESR at Week 36

Change From Baseline in DAS28-ESR at Week 40

Change From Baseline in DAS28-ESR at Week 44

Change From Baseline in DAS28-ESR at Week 48

Change From Baseline in DAS28-ESR at Week 52

Change From Baseline in DAS28-ESR at Early Withdrawal

Week 2

Week 4

Week 8

Week 12

Week 16

Week 20

Week 24

Week 28

Week 32

Week 36

Week 40

Week 44

Week 48

Week 52

Early withdrawal

Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response

Number of Participants Achieving an ACR50 Response

Number of Participants Achieving an ACR70 Response

Week 2: No response

Week 2: Moderate response

Week 2: Good response

Week 4: No response

Week 4: Moderate response

Week 4: Good response

Week 8: No response

Week 8: Moderate response

Week 8: Good response

Week 12: No response

Week 12: Moderate response

Week 12: Good response

Week 16: No response

Week 16: Moderate response

Week 16: Good response

Week 20: No response

Week 20: Moderate response

Week 20: Good response

Week 24: No response

Week 24: Moderate response

Week 24: Good response

Week 28: No response

Week 28: Moderate response

Week 28: Good response

Week 32: No response

Week 32: Moderate response

Week 32: Good response

Week 36: No response

Week 36: Moderate response

Week 36: Good response

Week 40: No response

Week 40: Moderate response

Week 40: Good response

Week 44: No response

Week 44: Moderate response

Week 44: Good response

Week 48: No response

Week 48: Moderate response

Week 48: Good response

Week 52: No response

Week 52: Moderate response

Week 52: Good response

Early Withdrawal: No response

Early Withdrawal: Moderate response

Early Withdrawal: Good response

Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR

Change at Week 4

Change at Week 8

Change at Week 12

Change at Week 16

Change at Week 20

Change at Week 24

Change at Week 28

Change at Week 32

Change at Week 36

Change at Week 40

Change at Week 44

Change at Week 48

Change at Week 52

Change at early withdrawal

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal

Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal

Percent Change From Baseline in Total TJC on 68 Joints at Week 52

Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal

Percent Change From Baseline in Total SJC on 66 Joints at Week 52

Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal

Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2

Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6

Baseline: Safety

Baseline: Discomfort

Baseline: Lack of efficacy

Baseline: Other

Baseline: Unknown

Week 2: Safety

Week 2: Discomfort

Week 2: Lack of efficacy

Week 2: Other

Week 2: Unknown

Week 4: Safety

Week 4: Discomfort

Week 4: Lack of efficacy

Week 4: Other

Week 4: Unknown

Week 8: Safety

Week 8: Discomfort

Week 8: Lack of efficacy

Week 8: Other

Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent	NCT02046603	Rheumatoid Arth...	Tocilizumab DMARDs Oral Corticoste... Methotrexate	18 Years -	Hoffmann-La Roche
A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent	NCT02046603	Rheumatoid Arth...	Tocilizumab DMARDs Oral Corticoste... Methotrexate	18 Years -	Hoffmann-La Roche

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