Predictive markers for response to interferon therapy in patients with multiple sclerosis

TypeofStudy:An open, retrospective study evaluating the predictive markers for response to interferon (IFN) therapy including Betaseron and IFNβ-1a in patients with multiple sclerosis.Patients:137 outpatients, 92 females and 45 males, age range 14-64 years. 29 patients received Betaseron (18 females and 11 males, mean age 39.2 years), 39 intramuscular IFNβ-1a (25 females and 14 males, mean age 38.0 years), 37 subcutaneous IFNβ-1a 22 mcg (27 females and 10 males, mean age 33.7 years), and 32 subcutaneous IFNβ-1a 44 mcg (22 females and 10 males, mean age 32.0 years).DosageDuration:250 mcg sc every other day. Duration: at least 3 years.Results:Results are given for the whole group of patients receiving IFN therapy without separate data for Betaseron. No difference was noted in the number of relapse-free patients between BAb-negative [58/104 (54%)] and BAb-positive [12/27 (44%)] patients, but there was a slight difference in the relapse-free survival (RFS). The BAb-positive group revealed a median time to 1st relapse of 10 months, while this was undefined in the BAb-negative group. Time to 1st relapse was remarkably increased in both MxA-positive (undefined) compared with MxA-negative (7 months) patients and in NAb-negative (undefined) compared with NAb-positive (8 months) patients. Among all patients, 70 (51%) were relapse-free. Of these, 65 (93%) were MxA-positive and 5 (7%) were MxA-negative. More MxA-positive patients were relapse-free compared with MxA-negative patients (57.5% vs 21%). Similar result was noted for NAb status, as 55.8% (67/120) of NAb-negative patients were relapse-free compared with 17.6% (3/17) of NAb-positive patients.AdverseEffects:No adverse events were mentioned.FreeText:The prognostic value of myxovirus-resistance-protein A messenger ribonucleic acid (MxA mRNA), neutralizing antibodies (NAbs), and Anti-anti-IFN antibodies or binding antibodies (BAbs) on the risk of having a new relapse was analyzed. Concomitant medication: high-dose intravenous methylprednisolone in patients experiencing relapse.AuthorsConclusions:The present study demonstrated for the first time that MxA mRNA quantification after 1 year of treatment with IFNβ has a strong prognostic value for the risk of experiencing new relapses. The prognostic value obtained using MxA mRNA is higher than that given by NAbs measurements. Therefore, to improve efficacy, the practice of MxA measurement might be the first choice in a monitoring strategy for IFNβ-treated patients. In addition, NAb and (less importantly) BAb evaluation might be used to predict the persistency of loss of biologic activity, distinguishing between reduced drug efficacy due to persistent inhibitory factors or treatment failure due to poor compliance.Indications:29 patients with multiple sclerosis (18 relapsing-remitting multiple sclerosis, 8 secondary progressive multiple sclerosis, and 3 relapsing progressive multiple sclerosis).