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.

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Cardiac valvular involvement associated with Wegener granulomatosis is uncommon. We describe a 17-year-old male adolescent who sought medical attention because of a sore throat, arthralgias, low-grade fever, and fatigue of 3 weeks' duration. A rash was noted on his elbows, hands, and ankles; subsequently, a crusting lesion was noted in his internal nares, and infiltrates were detected on chest radiography. Blood cultures were negative for pathogens. An echocardiogram disclosed mild left ventricular enlargement with grade 2 aortic insufficiency, and Wegener granulomatosis was diagnosed based on an antineutrophil cytoplasmic antibody titer of 1:512. When blood cultures are negative for aortic valve endocarditis, a high index of clinical suspicion and antineutrophil cytoplasmic antibody testing may lead to the diagnosis of acute aortic insufficiency associated with Wegener granulomatosis.

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