Etanercept in combination with sulfasalazine, hydroxychloroquine, or gold in the treatment of rheumatoid arthritis.

OBJECTIVE: To prospectively determine the efficacy and safety of etanercept in combination with sulfasalazine (SSZ), hydroxychloroquine (HCQ), and gold in the treatment of rheumatoid arthritis (RA). METHODS: A prospective open-label study enrolled 119 patients with RA who had active disease despite stable therapy with SSZ (n = 50), HCQ (n = 50), or intramuscular gold (n = 19). Primary efficacy endpoints consisted of American College of Rheumatology responses at 24 and 48 weeks. Safety was established at regularly scheduled visits. RESULTS: Patients in each etanercept combination showed significant improvement at both 24 and 48 weeks. Toxicity withdrawals by 48 weeks included gold (n = 1): proteinuria; HCQ (n = 5): septic wrist and bilateral pneumonia, rash, optic neuritis, breast cancer, squamous cancer of the tongue; and SSZ (n = 5): otitis media, elevated liver function indicators, pericarditis, rash, and gastroenteritis. The most common adverse events not requiring discontinuation from the study were injection site reactions (43% of patients) and upper respiratory type infections (34%). CONCLUSION: This study is the first to prospectively evaluate the safety of etanercept in combination with SSZ, HCQ, and gold in patients with RA. Etanercept in combination with SSZ, HCQ, or gold was efficacious and well tolerated, with a discontinuation rate of 9% (11/119) for adverse events at 48 weeks.

Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. RESULTS: Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. CONCLUSION: The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.