Intermittent, add-on treatment with an oral corticosteroid led to a significant drop in relapses among patients with multiple sclerosis who were previously relapsing on monotherapy with interferon-β in a controlled study with 130 patients.
If the efficacy of this cyclic regimen with methylprednisolone is confirmed in a second study now in progress, add-on, cyclic treatment with methylprednisolone “would be justified as routine therapy,” said Dr. Per Soelberg Sørensen, who reported his finding at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal.
Cyclic treatment with methylprednisolone as an add-on to interferon, mitoxantrone, or cyclophosphamide already is used off label at many multiple sclerosis (MS) clinics, said Dr. Sørensen, a professor in the department of clinical neuroscience and psychiatry at Rigshospitalet, Copenhagen.
The Nordic trial of methylprednisolone as add-on therapy to interferon-β (IFN-β) for the treatment of relapsing-remitting multiple sclerosis (NORMIMS), run by Dr. Sørensen and his associates at seven centers in Scandinavia, enrolled MS patients on long-term, subcutaneous treatment with interferon beta-1a who had at least one relapse during their previous year on treatment. In general, about 35% of MS patients on long-term treatment with IFN-β have relapses. The average relapse rate for all MS patients on a steady interferon regimen is 0.4 relapse events per year, Dr. Sørensen said in an interview.
The patients were randomized to receive either placebo or 200 mg of oral methylprednisolone daily for 5 days at 4 week intervals (a total monthly dose of 1 g). During the study, the interferon beta-1a regimen was maintained at a dosage of 44 mcg administered subcutaneously three times a week.
During 96 weeks of treatment, the annualized relapse rate of the 66 patients on methylprednisolone was 22%, compared with a 59% relapse rate among the 64 control patients on placebo, a statistically significant difference, said Dr. Sørensen.
During the study, 8 patients on methylprednisolone and 14 patients on placebo had a sustained increased in their disability based on at least a 1-point rise in their expanded disability status score. The average time it took for patients to have a sustained increase in their disability was 626 days for the patients on methylprednisolone and 376 days among those in the placebo group. The average number of active MS lesions seen with MRI in each patient during 1 year was 4.8 in those on the oral steroid and 5.4 in the control patients, a difference that just reached statistical significance. Methylprednisolone therapy was also well tolerated.
If methylprednisolone was used as cyclic, add-on therapy with IFN-β in routine practice, patients who failed to respond satisfactorily to the combination should be switched to other agents. Natalizumab and mitoxantrone are both approved as second-line drugs for MS and would be alternatives to consider, Dr. Sørensen said.
The second study of methylprednisolone added to interferon beta-1a in relapsing MS patients has treated more than 150 patients with the combination for 3 years. The methylprednisolone dosage used was higher, 500 mg/day for 3 days every 4 weeks (1.5 g/month), the maximum tolerable dose for this steroid, Dr. Sørensen said.
Results from this second study should be reported soon, according to Dr. Sørensen, who is also a coinvestigator for the second study.