OBJECTIVE: To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor alpha antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX.
METHODS: In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long-term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks.
RESULTS: An ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20-mg, 40-mg, and 80-mg adalimumab plus MTX groups (47.8%, 67.2%, and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50 response rates with the 20-mg, 40-mg, and 80-mg adalimumab dosages (31.9%, 55.2%, and 42.5%, respectively) were significantly greater than that with placebo (8.1%) (P = 0.003, P < 0.001, and P < 0.001, respectively). The 40-mg and 80-mg doses of adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively) that was statistically significantly greater than that with placebo (4.8%) (P < 0.001 and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab-treated patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab was safe and well tolerated; comparable numbers of adalimumab-treated patients and placebo-treated patients reported adverse events.
CONCLUSION: The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
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.
OBJECTIVES: Fatigue is an important systemic symptom of rheumatoid arthritis (RA) but has rarely been evaluated consistently after initiation of treatment in RA patients. This study examined the effects of adalimumab (HUMIRA, Abbott Laboratories, Abbott Park, IL, USA), a fully human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody, on reducing fatigue in patients with RA.
METHODS: A total of 1526 patients with RA were enrolled in 3 randomized, placebo-controlled clinical trials of adalimumab versus placebo plus methotrexate (MTX) or placebo plus standard antirheumatic therapies. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale questionnaire (which has been validated in RA) at baseline, mid-study, and at the end of the study. Logistic regression models were constructed using baseline demographic variables to test for treatment effect. In addition, sensitivity analyses were performed to determine the robustness of the data.
RESULTS: At baseline in the 3 trials, patients' fatigue ranged from 27.9-29.7, representing considerable fatigue on the FACIT fatigue scale. Fatigue was significantly and consistently reduced in adalimumab-treated patients in the 3 clinical trials. Relative to placebo plus MTX, the adalimumab 40-mg-every-other-week dosage group reported statistically significantly less fatigue at all time points post-baseline. Improvements between adalimumab and placebo ranged from 3-7 points across all 3 trials, with a 3-4-point change representing a minimum clinically important difference.
CONCLUSION: Adalimumab treatment was shown to significantly reduce fatigue in patients with moderate to severe RA. Changes in fatigue in all 3 trials were found to be clinically important.
