A Study of Tocilizumab With or Without Methotrexate in Patients With Rheumatoid Arthritis.

Study Overview
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Brief Summary
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This open-label, single-arm, non-randomized study will evaluate the adherence and persistence to tocilizumab therapy in patients with moderate to severe active rheumatoid arthritis, who have an inadequate clinical response to non-biologic DMARDs. Patients will receive tocilizumab 8 mg/kg as intravenous infusion once every 4 weeks in combination with methotrexate or in case of intolerance to methotrexate as monotherapy. The anticipated time of study treatment is 6 months. The target sample size is 20-50 patients.

Official Title
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Evaluation of Adherence and Persistence to Tocilizumab in Combination With Methotrexate or Tocilizumab Monotherapy in Patients With Moderate to Severe Active Rheumatoid Arthritis in Local Environment.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >/= 18 years of age moderate to severe active rheumatoid arthritis inadequate response, or intolerance to previous therapy with one or more traditional DMARDs DAS >3.6 pneumology examination (including chest x-ray and quantiferon) Exclusion Criteria: < 18 years of age active infection active tuberculosis uncontrolled hyperlipoproteinaemia demyelinating disorders concomitant anti-TNF drugs history of intestinal ulceration and diverticulitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* tocilizumab 8 mg/kg intravenous infusion once in 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Adherent to Original Treatment | Adherence rate to original treatment according to the protocol included all participants that received the study drug beginning from Week 8 and remaining until the end of the study. This number represents participants with no changes in treatment protocol, participants with treatment discontinuation, and participants with dose reduction, but not participants that withdrew from the study prematurely. | Week 24 | 
| Percentage of Participants Receiving Less Than or Equal to (≤) 1 Dose of Study Drug Who Discontinued Treatment for Any Reason |  | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants Receiving Greater Than (>) 1 Dose Who Discontinued Treatment for Any Reason |  | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants Withdrawing From the Study Prematurely for Any Reason |  | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With Dose Reduction to Tocilizumab 4 mg/kg |  | Weeks 0, 4, 8, 12, 16, and 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score Based on 28-Joint Count (DAS28) | DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2 equals (=) low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity. | Weeks 0, 4, 12, and 24 | 
| Patient Global Assessment of Pain | Participants were asked to rate their pain using a 0 to 100 mm visual analog scale (VAS), where 0 mm = no pain and 100 mm = worst possible pain. The participant was asked to mark the line corresponding to their perceived level of pain and the distance in mm from the left edge of the scale was measured. | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Patient Global Assessment of Disease Activity | The participant's assessment of disease activity was performed using a 100 mm VAS ranging from no activity (0) to maximal activity (100). The participant was asked to mark the line corresponding to their perceived level of disease activity and the distance in mm from the left edge of the scale was measured. | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Physician's Global Assessment of Disease Activity | Physician's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The physician was asked to mark the line corresponding to their perceived level of the participant's disease activity and the distance in mm from the left edge of the scale was measured. | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Swollen Joint Count (SJC) | The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Joints were rated as 0=not swollen or 1=swollen. The total number was calculated from all the joints for a maximum score of 28. | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Tender Joint Count (TJC) | The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Joints were rated as 0=not tender or 1=tender. The total number was calculated from all the joints for a maximum score of 28. | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Erythrocyte Sedimentation Rate (ESR) | ESR indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. | Weeks 0, 4, 12, 20, and 24 | 
| C-Reactive Protein (CRP) | CRP is an acute phase protein. Levels of CRP increase with inflammation. | Weeks 0, 4, 12, 20, and 24 | 
| Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | The HAQ-DI was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. | Weeks 0, 4, 8, 12, 16, 20, and 24 | 
| Short Form-36 (SF-36) | The SF-36 measures the impact of disease on overall quality of life and consists of 8 subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. | Weeks 0, 12, and 24 |