Combination Therapy for Relapsing-Remitting MS Speaker: Silva Markovic-Plese, MD, Clinical Fellow, Neuroimmunology Branch, the National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland.
Interferon beta-1b (INF-beta-1b) (Betaseron, Berlex) and azathioprine (Imuran drug, Prometheus) combination therapy appears to offer an effective treatment approach in patients with relapsing-remitting multiple sclerosis (RRMS) who are refractory to treatment with INF beta-lb alone.
To reach this conclusion, a study was carried out to assess the effectiveness of azathioprine in augmenting the response to INF beta-lb in a group of patients with RRMS. This group of individuals continued to have active disease while being maintained on INF beta-lb monotherapy. To this end, a subset of six patients refractory to INF beta-lb therapy was identified from a longitudinal study of RRMS patients treated with INF beta-lb. These patients had been treated with INF beta-lb for three to 35 months (median: 17 months), with continuously high disease activity (median: l2.69; Gadolinium [Gd]-enhancing lesions and median exacerbation rate, l.63). The six patients were studied on INF beta-lb 8 IMU subcuta-neously on alternate days and oral canadian azathioprine l.5 mg/kg daily for six to 48 months (median: l5 months). Patients were evaluated monthly with serial magnetic resonance imaging (MRI) scans and comprehensive neurological evaluations. The number of Gd-enhancing MRI lesions was used as a primary outcome measure. Clinical outcome measures (expanded disability status score (EDSS), progression index [change in EDSS per year], and exacerbation rates).
In this group of patients, adding azathioprine to INF beta-lb therapy resulted in a reduction of new Gd-enhancing lesions from 6.83 to 3.37. Also, the number of total Gd-enhancing lesions was reduced from l2.67 to 3.87 during the combination therapy, compared to INF beta-lb monotherapy. Both of these reductions between combination therapy and baseline were statistically significant. Thirteen months after the addition of generic azathioprine to INF beta-lb, complete clinical responses were reported. At four years’ follow-up (one patient had been followed for eight years), the patients, four of whom had recurrent exacerbations during INF beta-lb monotherapy, had a sharp reduction in the number of relapses during the combination therapy, and all were, for the most part, exacerbation-free.