ABSTRACT
BACKGROUND: Azathioprine is an immunosuppressive agent that reduces relapse rates in patients with multiple sclerosis (MS), but its efficacy in suppressing new brain lesions has never been evaluated. OBJECTIVE: To evaluate the efficacy of azathioprine therapy on new brain lesion suppression in MS. DESIGN: Open-label treatment vs baseline study. SETTING: Outpatient MS clinical center at a university hospital. PATIENTS: Fourteen patients with relapsing-remitting MS of short duration and at least 3 gadolinium-enhancing (Gd+) brain lesions observed within 6 months before treatment. INTERVENTION: Azathioprine, up to 3 mg/kg daily, individually adjusted according to blood lymphocyte number and the occurrence of adverse events. MAIN OUTCOME MEASURES: Brain Gd+ lesions evaluated by monthly magnetic resonance imaging for 6 months before and 6 months during treatment and new T2 lesions evaluated during the same periods and after an additional 6 months. RESULTS: The treatment reduced to 0 the median Gd+ lesion number and volume per magnetic resonance image (P<.001 for both), resulting in a Gd+ lesion number reduction of 50% or more in 12 of 14 patients (P<.01). An equivalent reduction in the new T2 lesion number was observed (P<.02); this activity also persisted during the additional treatment period evaluated using this outcome measure (P<.01). The median azathioprine dose administered (2.6-2.8 mg/kg daily) reduced the mean blood lymphocyte count to 57% of the baseline value. Adverse events were transient or reversible with dose adjustment. CONCLUSIONS: This study indicates for the first time that azathioprine, administered at lymphocyte-suppressing doses, is effective in reducing MS new brain inflammatory lesions and is well tolerated.
