Direct Comparison of Azathioprine and beta Interferon Efficacy in Multiple Sclerosis

Abstract OBJECTIVE: To compare efficacy and safety of azathioprine (AZA) with the currently available IFNs on clinical and MRI outcome measures of relapsing-remitting multiple sclerosis (MS), through a multicenter randomized controlled trial (RCT). BACKGROUND: Following approval of Beta Interferons (IFN) for multiple sclerosis (MS), Azathioprine (AZA) has mainly been used as a second line treatment, although direct comparison of these medications has never been carried out. DESIGN/METHODS: Eligible patients (n=150; relapsing-remitting MS; > 2 relapses in the last 2 years) were randomly assigned to AZA or to an IFN and followed for 2 years. Primary outcome was efficacy on relapse rate. Key secondary outcome was number of new brain lesion, measured by MRI via T2 weighted sequences. For MRI evaluation 122 patients were included. The efficacy of these treatments was compared by applying a non-inferiority design according to published guidelines. RESULTS: As for baseline characteristics, the randomization generated comparable groups (n= 77 and 73). Clinical evaluation indicates that annualized relapse rate was lower in the AZA than in the IFN group and non-inferiority analysis showed that AZA exerts on this outcome measure at least the same effect of IFNs (0.67%, one sided 95% C.I.= 0.96; p= 0.03). New T2 lesion number analyzed in 97 patients, was similar in both groups indicating that AZA maintains also on this outcome at least 73% of the IFN efficacy (p= 0.05). Number of patients with adverse events (AE) and patients who discontinued treatment for AEs were similar in both the treatment groups although total AE number was higher in the AZA treated group. CONCLUSIONS: These data indicate for the first time, that in relapsing remitting MS AZA is at least as effective as IFNs on clinical outcome measures and that its efficacy on suppressing new brain lesions is equivalent to that of the IFNs.