Azathioprine and Interferon β1a in Relapsing-Remitting Multiple Sclerosis Patients: Increasing Efficacy of Combined Treatment

Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon β (IFN-β) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed. We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-β 1a combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups: 8 previously untreated patients (subgroup A) with at least 2 years of natural course of the disease, 8 patients (subgroup B) previously treated with AZA for 2 years and 7 patients (subgroup C) previously treated with IFN-β 1a for 2 years. The baseline Expanded Disability Status Scale (EDSS) ranged from 2 to 4 in all subgroups. All patients completed 2 years of combined treatment with a dose of AZA adjusted to reduce lymphocyte count down to 1,000 ± 100/µl in association with IFN-β 1a at a dose of 6 MIU every other day. The mean number of relapses during the combined treatment period was significantly lower than that observed before combined therapy in all the three subgroups. Also, the mean ΔEDSS score was significantly lower during combined treatment than in monotherapy in subgroups B and C. Moreover, after 2 years of combined treatment, the number of new T 1 hypointense lesions, the number and volume of proton density/T 2 hyperintense lesions and the gadolinium enhancement of T 1 hypointense lesions were significantly lower than before combined treatment. After 2 years of treatment, this combination therapy appears to be safe and well tolerated and no serious side effects were reported. Despite some limitations of our study design, the information regarding efficacy, safety and tolerance of the association of AZA and IFN-β is most encouraging.