Brand Name: Remicade
Active Ingredient: infliximab
Indication: Treatment of rheumatoid arthritis when administered with methotrexate
Company Name: Centocor, Inc.
Availability: Approved for this indication in November 1999 (had already been approved for treating Crohn’s disease)
Remicade (infliximab), a drug approved by the FDA in 1998 for the treatment of Crohn’s disease, was recently approved for the treatment of rheumatoid arthritis when administered with methotrexate, the standard treatment for this inflammatory disease. The drug offers hope for patients with rheumatoid arthritis in whom methotrexate does not offer adequate relief of symptoms.
How It Works
Tumor necrosis factor (TNF) alpha is a cytokine with a significant role in the inflammatory process in rheumatoid arthritis. Remicade works by binding to TNF-alpha and inhibiting the cytokine’s ability to bind to its receptors, thus neutralizing it. Animal studies in transgenic mice that developed polyarthritis showed that treatment with infliximab after disease onset actually allowed eroded joints to heal. Remicade reduces the infiltration of inflammatory cells into inflamed areas of joints, as well as expression of cell-adhesion molecules and tissue degradation that are also part of the inflammatory process.
Remicade (infliximab): Clinical Study Results
The safety and efficacy of Remicade when given in conjunction with methotrexate were demonstrated in a multicenter, randomized, double-blind, placebo-controlled study of 428 patients with active rheumatoid arthritis who were already taking methotrexate (the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy, or ATTRACT). The median disease duration was 8.4 years, with the median number of swollen and tender joints being 20 and 31, respectively. All patients had been receiving methotrexate for 6 months or more and were on a stable dose of 12.5 mg per week or more for 4 weeks prior to the study, a dose that was continued throughout the study.
Patients received placebo, 3 mg/kg, or 10 mg/kg of Remicade (infliximab) by intravenous infusion at 0, 2, and 6 weeks, followed by additional infusions every 4 to 8 weeks thereafter. Concurrent use of other anti-inflammatory drugs was permitted. The primary endpoint was the proportion of patients at week 30 who attained an improvement in signs and symptoms as measured by the American College of Rheumatology (ACR). An ACR 20 response was defined as at least a 20% improvement in both tender and swollen joint counts and in three of the following criteria: physician global assessment, patient’s global assessment, functional/disability measure, visual analog pain scale, and erythrocyte sedimentation rate.
At week 30, 43/86 (50%) of patients treated every 8 weeks with 3 mg/kg of Remicade plus methotrexate attained an ACR 20 response, 27% attained an ACR 50 response, and 8% attained an ACR 70 response. The corresponding values for patients receiving placebo plus methotrexate were 18/88 (20%), 5%, and 0%, respectively – a significant difference. Patients receiving 3 mg/kg Remicade plus methotrexate also showed superior improvement in all ACR response components except disability. Higher doses and/or more frequent administration did not result in higher response rates.
As a result of the clinical data, the recommended dose of Remicade is an initial 3 mg/kg dose given as an intravenous infusion, followed with additional 3 mg/kg doses 2 and 6 weeks after the first infusion, and then every 8 weeks thereafter, in combination with methotrexate. The efficacy of Remicade without concurrent methotrexate is limited.
What the Patient Should Know
Serious infections, including sepsis and fatal infections, have been reported in patients receiving TNF-alpha-blocking agents. Many of these infections have occurred in patients receiving concomitant immunosuppressive therapy that could predispose them to infections. Caution should be exercised when considering using Remicade in patients with a chronic infection or a history of recurrent infection. Patients who have an active clinically important infection should not receive Remicade, and those who develop an infection during Remicade treatment should be monitored closely. Other adverse side effects associated with Remicade include dyspnea, urticaria, and headache.