Treatment guidelines and positive trials at ECTRIMS

The first European guidelines for the treatment of multiple sclerosis (MS) were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in London in September 2016. The presentation of the guidelines rounded off a meeting that also saw a host of promising results from trials of therapies targeted at the degenerative stage of MS.

The treatment guidelines were developed in a collaboration between the European Academy of Neurology and ECTRIMS, and are based on the latest global evidence and the therapies that are approved for use in Europe. Among the agreed recommendations is advice to initiate disease-modifying therapy before MS diagnosis in patients with clinically isolated syndrome and MRI abnormalities. Also agreed is that patients with primary progressive MS should receive ocrelizumab, although inclusion of this recommendation in the published guidelines will depend on the expected upcoming approval of this drug in Europe. For established MS, the guidelines leave the choice of therapy to the treating neurologist, but recommend that they take into account a number of factors, including patient history, age, the level of disease activity, comorbidities, and personal preference. Although the initial recommendations have been agreed by the steering group, the guidelines are yet to be finalized and published.

The clinical trial highlights included the results of the phase III EXPAND study of the S1P receptor modulator siponimod, which inhibits the egress of lymphocytes from lymph nodes, in secondary progressive MS (SPMS). The placebo-controlled study included 1,651 patients with SPMS, and showed that siponimod reduced disability progression by 21% at 3 months and 26% at 6 months. Subgroup analysis showed that the effect was greatest in patients who had experienced relapses in the previous 2 years, but was still significant in patients without relapse.

More promising results in SPMS were reported from a pilot trial of lipoic acid, in which 51 patients were administered 1,200 mg lipoic acid per day or a placebo for 96 weeks. The yearly rate of whole-brain atrophy was 66% lower in treated patients than in patients who received placebo. The investigators now plan to undertake a larger trial to confirm the neuroprotective effects.

Results of the ENHANCE study of prolonged-release fampridine were also encouraging. This study included 646 patients, all of whom had Expanded Disability Status Scale scores of 4–7 at baseline. In this population, prolonged-release fampridine significantly improved walking, balance and mobility. The effect was maintained throughout the 24 weeks of the study, indicating that this therapeutic approach could benefit patients with MS who are already disabled.

Finally, the first results from the FLUOX-PMS trial of fluoxetine for the prevention of disability progression were presented. Although no significant effect was seen, there was a trend for the drug to slow disability progression, with the biggest effect on walking ability.