More recent trials have shown that relapse rates are similar with the use of azathioprine or methotrexate (25 mg/week orally) and, surprisingly and disappointingly, higher with mycophenolate mofetil (2,000 mg/day) than with azathioprine.10,11 The latter study thereby provided some unintended reassurance that standard maintenance therapy is useful. Leflunomide at 30 mg/day was superior to methotrexate at 20 mg/week for remission maintenance in one small study, but the safety of that dose and, conversely, the efficacy of the more usual dose (20 mg/day) are unknown. Another study found that the addition of etanercept to standard maintenance therapy did not reduce relapse rates.12,13 Thus, azathioprine remains the best choice for patients with significant renal dysfunction or liver disease, methotrexate is an appropriate alternative for all other patients, and either leflunomide or mycophenolate remain options in the event that the other two drugs are contraindicated, poorly tolerated, or ineffective for a given patient. Whether there is a role for high-dose sulfamethoxizole-trimethoprim (one double-strength tablet twice daily) in addition to an immune-suppressive drug continues to be a source of debate, but this drug at this strength should not be used in combination with methotrexate.
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