A RANDOMIZED, CONTROLLED, SAFETY TRIAL OF ADALIMUMAB (D2E7), A FULLY HUMAN ANTI-TNF MONOCLONAL ANTIBODY, GIVEN TO RA PATIENTS IN COMBINATION WITH STANDARD RHEUMATOLOGIC CARE: THE STAR (SAFETY TRIAL OF ADALIMUMAB IN RHEUMATOID ARTHRITIS) TRIAL

Background: A randomized, controlled safety trial of adalimumab (D2E7, Abbott), a fully human anti-TNF monoclonal antibody, was designed to mirror actual clinical practice. Patients with active rheumatoid arthritis (RA) were given adalimumab plus concomitant DMARDs, corticosteroids, and/or NSAIDs to assess the safety of this combination.Methods: The STAR (Safety Trial of Adalimumab in Rheumatoid arthritis) trial was a 24-week, double-blind, placebo-controlled, randomized trial and compared the addition of adalimumab 40 mg subcutaneously (sc) every other week or placebo to pre-existing antirheumatic therapy. All patients were allowed to continue their DMARDs (none, one, or multiple), corticosteroids (=<10 mg/day of prednisone equivalent), and/or NSAIDs. Eligibility requirements included age >18, RA for >=3 months, active disease defined by >=6 swollen joints and >=9 tender joints. After 12 weeks, changes in RA therapy were permitted, including the addition of other DMARDs, increase in DMARD dose, or addition of low-dose corticosteroids. The primary endpoints of this study were safety-related, including the number of adverse events, serious adverse events, infections, and serious infections.Results: A total of 636 patients were randomized to adalimumab 40 mg sc every other week or placebo. Baseline demographic characteristics were similar between treatment groups. The mean characteristics included: age 55.4 years, 79.4% female, duration of RA 10.4 years, TJC 27.4, SJC 21.1, and CRP 1.5 mg/dL. Concomitant DMARD therapy was used by 83.5% of patients (56.0% used one, 27.5% used two to four concomitant DMARDs). The percent of patients on DMARDs used was: MTX 59.3%, antimalarials 24.7%, leflunomide 13.4%, sulfasalazine 9.7%, and parenteral gold 5.8%. The overall incidence of adverse events (AEs) is shown in the table below. Injection-site reactions were increased in the adalimumab arm (8.8% vs 0.6% with placebo). No cases of tuberculosis or opportunistic infections were seen. Adalimumab (318 Pts) Placebo (318 Pts) Adalimumab vs N (%) N (%) Placebo P ≤ 0.05 AE 275 (86.5) 263 (82.7) NS SAE 17 (5.3) 22 (6.9) NS Death 1 (0.3) 0 (0) NS Severe or life-threatening AE 38 (11.9) 49 (15.4) NS AE leading to withdrawl 9 (2.8) 7 (2.2) NS Infections 166 (52.2) 157 (49.4) NS Serious Infections* 4 (1.3) 6 (1.9) NS *Requiring IV antibiotics or hospitalization. *Requiring IV antibiotics or hospitalization.Conclusion: The rates of adverse events, serious adverse events, infections, or serious infections compared with placebo did not change when adalimumab was added to pre-existing antirheumatic therapy. This study demonstrates that adalimumab is safe and well tolerated when given to a heterogeneous group of patients with RA in addition to multiple other antirheumatic therapies.Citation: , volume , supplement , year 2002, page Session: Rheumatoid arthritis – Treatment 2