EXTENDED REPORT

Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4 year extended study

M E Weinblatt¹, E C Keystone², D E Furst³, A F Kavanaugh⁴, E K Chartash⁵, O G Segurado⁶

¹ Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA, USA
² The Rebecca MacDonald Centre for Arthritis and Autoimmunity, Mount Sinai Hospital, University of Toronto, Toronto, Canada
³ Rheumatology Division, Geffen School of Medicine at the University of California–Los Angeles (UCLA), Los Angeles, CA, USA
⁴ Center for Innovative Therapy, University of California–San Diego, Division of Rheumatology, Allergy and Immunology, La Jolla, CA, USA
⁵ Immunology, Abbott Laboratories, Parsippany, NJ, USA
⁶ Immunology, Abbott Laboratories, Abbott Park, IL, USA

Correspondence to:
Dr M E Weinblatt
Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, 75 Francis St., Boston, MA, USA; mweinblatt{at}partners.org

Objective: To evaluate the efficacy and safety of adalimumab plus methotrexate (MTX) given for up to 4 years in patients with active, longstanding rheumatoid arthritis.

Methods: Patients responding inadequately to MTX were entered into a 24 week, controlled study (ARMADA) with adalimumab plus MTX or placebo plus MTX, and some were enrolled in a subsequent open label extension. The efficacy and safety of treatment were evaluated. Additional analyses were made for those patients whose corticosteroid and/or MTX dosages were adjusted during the extension.

Results: Of 271 patients in the original ARMADA trial, 262 received at least one dose of adalimumab and were evaluated. At the time of analysis, 162/262 (62%) patients had remained in the study and received treatment for a mean of 3.4 years. Withdrawals were for lack of efficacy (8%), adverse events (12%), and other reasons (18%). In 147 patients who completed 4 years’ treatment, efficacy achieved at 6 months was maintained. At 4 years, 78%, 57%, and 31% had achieved ACR20/50/70; 43% achieved clinical remission (DAS28 <2.6); and 22% had no physical function abnormalities (HAQ = 0). Results were similar for 196 patients who received treatment for 2–4 years. Efficacy was maintained in many patients when dosages were decreased (corticosteroids (51/81 (63%) patients), MTX (92/217 (42%)), or both (25/217 (12%))). Serious adverse events were comparable during open label treatment and the controlled phase. Serious infections occurring during open label treatment and the blinded period were similar (2.03 v 2.30 events per 100 patient-years, respectively).

Conclusions: Adalimumab plus MTX sustained clinical response and remission in patients with RA during 4 years. The safety profile during the first 6 months was similar to that after 4 years’ follow up. Reduction of corticosteroid and/or MTX dosages did not adversely affect long term efficacy.

Abbreviations: ACR, American College of Rheumatology; AEs, adverse events; CI, confidence interval; CRP, C reactive protein; DAS28, 28 joint count Disease Activity Score; DMARDs, disease modifying antirheumatic drugs; HAQ, Health Assessment Questionnaire; LOE, lack of efficacy; MTX, methotrexate; PPD, purified protein derivative; RA, rheumatoid arthritis; SIR, standardised incidence ratio; SJC, swollen joint count; TJC, tender joint count; TNF, tumour necrosis factor

Keywords: rheumatoid arthritis; adalimumab; treatment; tumour necrosis factor antagonists; open label extension studies

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