Prospective Study on Intensive Early Rheumatoid Arthritis Treatment

Study Overview
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Brief Summary
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Hypothesis: Early intensive treatment with anti-TNF agent plus methotrexate plus high dose prednisone may increase remission rate and may induce stable remission in Rheumatoid Arthritis Objective: to evaluate induction of remission using adalimumab, prednisone and methotrexate and maintenance of remission after discontinuation of adalimumab and prednisone

Detailed Description
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Treatment group A 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + prednisone 50 mg/d tapered to 6.25 mg 6 - 12 months: Adalimumab 40 mg eow plus methotrexate 20 mg weekly group B 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + placebo 6 - 12 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly Follow up period - Open Label phase: Patients achieving clinical remission will be than treated only with MTX and observed for another 12 months period. Patients who do not achieve clinical remission or patients who will experience a relapse of the disease will be treated according to standard of care (SOC) modalities.

Official Title
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A Phase IV Multicenter, Randomized, Double-blind Study. prospeCtive Study on Intensive Early Rheumatoid Arthritis Treatment With adalimUmab: Induction of REmission and Maintenance

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: adalimumab, plus prednisone
* Drug: adalimumab plus placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active rheumatoid arthritis diagnosed for at least 6 weeks, but no more than 1 year, according to the revised 1987 ACR criteria Naïve to treatment with MTX Swollen joint count (SJC) > 8 tender joint count (TJC) > 8 At screening CRP > 1.5 mg/dL (15 mg/L) or ESR ≥ 28 mm/h ≥ 1 joint erosion or RF positivity or anti-CCP positivity Age 18-70 years. Exclusion Criteria: Rheumatic autoimmune disease other than RA Functional class IV Any surgical procedure within 12 weeks prior to baseline or planned during the study. Pregnancy or breast feeding. Evidence of significant concomitant disease Primary or secondary immunodeficiency active infection of any kind History of previously untreated infection with mycobacterium tuberculosis or current treatment for same. History of cancer Any history or presence of congestive heart failure (CHF) (New York Heart Association classification for CHF: Class III or IV). Any history of myocardial infarction within 5 years. History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of adalimumab or methotrexate. Positive serology for hepatitis B or C indicating active infection. Hemoglobin < 8.0 g/dL. Absolute neutrophil count (ANC) < 1.5 x 103/L. Liver function abnormality

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group A<br>adalimumab 40 mg subcutaneous injections every other week from baseline to month 12 methotrexate orally weekly at initial dose of 10 mg rising to 20 mg weekly over 4 weeks in 2.5 mg increments, continued up to month 24. prednisone orally 50 mg daily, gradually tapered up to 6.25 mg at week 7 and stopped at month 6 | Drug: adalimumab, plus prednisone<br>* adalimumab 40 mg/sc every 2 weeks plus methotrexate 20 mg/po every week plus placebo or prednisone 50 mg/po day then reduced to 6.25/po day<br>* Other names: deltacortene (prednisone);|
| Placebo Comparator: group B<br>adalimumab 40 mg subcutaneous injections every other week from baseline to the end of month 12 methotrexate orally oweekly at an initial dose of 10 mg rising to 20 mg weekly over 4 weeks in 2.5 mg increments, continued up to month 24. placebo orally, stopped at month 6 | Drug: adalimumab plus placebo<br>* adalimumab 40 mg/sc every 2 weeks plus methotrexate 20 mg/po every week plus placebo daily for 6 months<br>* Other names: humira (adalimumab);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the proportion of subjects who achieve remission at week 52 after treatment, as defined by DAS 28 </= 2.6 |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| subjects who maintain stable remission at 24 months; ACR 20,50,70 at month 4,8,12,24; DAS 28 at month 4,8,12,24; HAQ at week 0,4,8,12,24; radiographic progression at months 12, 24; safety of different treatment regimens |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rheumatoid arthritis, clinical remission