A Study of Tocilizumab (RoActemra/Actemra) Versus Adalimumab in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This randomized, blinded, parallel arm study evaluated the efficacy and safety of tocilizumab (RoActemra/Actemra) versus adalimumab as monotherapy in patients with rheumatoid arthritis who are intolerant of methotrexate or where continued treatment with methotrexate was considered inappropriate. Patients were randomized to receive either tocilizumab 8 mg/kg intravenously (iv) every 4 weeks plus placebo subcutaneously (sc) every 2 weeks, or adalimumab 40 mg sc every 2 weeks plus placebo iv every 4 weeks. Treatment was anticipated to last 24 weeks. With regard to the blind, the study nurse was unblinded due to the nature of the treatment administration, but the investigator and the patient remained blinded.

Official Title
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A Multi-center, Randomized, Blinded, Parallel-group Study of the Reduction of Signs and Symptoms During Monotherapy Treatment With Tocilizumab 8 mg/kg Intravenously Versus Adalimumab 40 mg Subcutaneously in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tocilizumab
* Drug: Adalimumab
* Drug: Placebo to tocilizumab
* Drug: Placebo to adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, ≥ 18 years of age. Rheumatoid arthritis of > 6 months duration. Intolerant of methotrexate or continued treatment with methotrexate is considered inappropriate. All disease-modifying anti-rheumatic drugs (DMARD) are to be withdrawn prior to receiving study drug. Weight ≤ 150 kg. Exclusion Criteria: Major surgery (including joint surgery) within 12 weeks prior to baseline or planned major surgery within 6 months after baseline. History of or current inflammatory joint disease other than rheumatoid arthritis (RA). Treatment with a biologic agent at any time prior to baseline. Intra-articular or parenteral corticosteroids ≤ 4 weeks prior to baseline. Active current infection or history of recurrent bacterial, viral, fungal or mycobacterial infection.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab 8 mg/kg<br>Patients received 6 infusions of tocilizumab 8 mg/kg intravenously every 4 weeks and 12 injections of placebo to adalimumab subcutaneously every 2 weeks. | Drug: Tocilizumab<br>* The maximum dose was 800 mg for patients weighing more than 100 kg. Tocilizumab was infused into an arm vein over a 1-hour period.<br>* Other names: Actemra;Drug: Placebo to adalimumab<br> <br> |
| Active Comparator: Adalimumab 40 mg<br>Patients received 12 injections of adalimumab 40 mg subcutaneously every 2 weeks and 6 infusions of placebo to tocilizumab intravenously every 4 weeks. | Drug: Adalimumab<br> <br> Drug: Placebo to tocilizumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28) | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. The analysis was adjusted for stratification factors of duration of RA (≤ 2 years and > 2 years) and region (US and non-US). | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With a Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Week 24 | The percentage of patients who achieved remission of their rheumatic arthritis at Week 24, as measured by a DAS28 score < 2.6, is reported. | Week 24 | 
| Percentage of Patients With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Week 24 | The percentage of patients who had low rheumatic arthritis disease activity at Week 24, as measured by a DAS28 score of 3.2 or less, is reported. | Week 24 | 
| Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24 | Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line no disease activity [symptom-free and no arthritis symptoms] and the extreme right end maximum disease activity; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line no pain and the extreme right end unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate. | Baseline to Week 24 | 
| Percentage of Patients With a European League Against Rheumatism (EULAR) Good Response at Week 24 | Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2. | Baseline to Week 24 | 
| Percentage of Patients With a European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24 | Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2. | Baseline to Week 24 |