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

• Published in: Annals of the rheumatic diseases Vol. 65; no. 6; pp. 753 - 759
• Main Authors: Weinblatt, M E, Keystone, E C, Furst, D E, Kavanaugh, A F, Chartash, E K, Segurado, O G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2006; BMJ; Elsevier Limited; BMJ Group
• Subjects: 28 joint count Disease Activity Score; ACR; Adalimumab; Adult; adverse events; AEs; Aged; Aged, 80 and over; American College of Rheumatology; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; C reactive protein; Clinical trials; confidence interval; CRP; DAS28; disease modifying antirheumatic drugs; Diseases of the osteoarticular system; DMARDs; Drug Administration Schedule; Drug dosages; Drug Therapy, Combination; Extended Report; Female; HAQ; Health Assessment Questionnaire; Humans; Immunomodulators; Infections; Inflammatory joint diseases; Laboratories; lack of efficacy; LOE; Long term; Male; Medical sciences; methotrexate; Methotrexate - adverse effects; Methotrexate - therapeutic use; Middle Aged; MTX; open label extension studies; Pharmacology. Drug treatments; PPD; Prospective Studies; purified protein derivative; Remission Induction; Rheumatoid arthritis; SIR; SJC; standardised incidence ratio; swollen joint count; tender joint count; Time Factors; TJC; TNF; treatment; Tumor necrosis factor-TNF; tumour necrosis factor; tumour necrosis factor antagonists; Antineoplastic agent; Human; Toxicity; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Monoclonal antibody; Long term; Antifolate; Immunomodulator; Chronic; Antimetabolic; Rheumatoid arthritis; Anticytokine; Adalimumab; Methotrexate; Tumor necrosis factor α
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2005.044404

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.