Treatment de-escalation after mitoxantrone therapy: results of a phase IV, multicentre, open-label, randomized study of subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis.

OBJECTIVE: The objective of this study was to assess the effect of treatment with interferon (IFN) ß-1a, 44 µg subcutaneously (sc) three times weekly (tiw), on clinical and magnetic resonance imaging (MRI) outcomes in patients with relapsing multiple sclerosis (MS) following mitoxantrone therapy. METHODS: This was an open-label, randomized, multicentre, rater-blinded, 96-week observational study conducted in Germany. Clinically stable patients with relapsing forms of MS, who had discontinued mitoxantrone treatment 1-6 months before study entry, were randomized to IFN ß-1a sc 44 µg tiw, or no treatment. The primary endpoint was time to first relapse. Secondary endpoints included the number of relapse-free patients, disease activity assessed by MRI and time to 3-month confirmed Expanded Disability Status Scale (EDSS) progression, all at week 96. RESULTS: A total of 30 patients were randomized (intent-to-treat population: 14 IFN ß-1a, 15 untreated; one patient from the safety population discontinued the study after 25 days owing to an adverse event and without providing any postbaseline efficacy data, and was thus excluded from the intent-to-treat population). Overall, 71.4% (10/14) of patients in the IFN ß-1a group remained relapse free over 96 weeks, versus 46.7% (7/15) in the untreated group (p = 0.26). IFN ß-1a delayed the time to first relapse versus no treatment (p = 0.14); time to first relapse (25th percentile) was 95.4 (IFN ß-1a) versus 46.0 weeks (no treatment). Confirmed EDSS progression was observed in five patients in each treatment group. Mean change in EDSS score was 0.3 in both groups (p = 0.79). Changes in the number or volume of T1 and T2 lesions at week 96 were not significantly different between treatment groups (p > 0.05). There were no new or unexpected adverse events related to IFN ß-1a treatment. CONCLUSIONS: Several endpoints appeared to show a benefit of IFN ß-1a treatment, but no significant differences could be detected owing to the small sample. Therefore, these data only permit, at best, tentative conclusions about the disease course in patients with MS after de-escalation from mitoxantrone and continuation with or without IFN ß-1a. Larger confirmatory studies are required.