In October 2018, over 9,400 delegates gathered in Berlin for the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) — the world’s largest conference on multiple sclerosis (MS). Recurring themes during the congress included the application of real-world data to treatment decision-making, the use of neurofilament light chain as a biomarker for neurodegeneration, and the ongoing challenge of treating progressive forms of MS.

The Late-Breaking News session featured a number of notable ‘firsts’, including the first demonstration of a reduction in MS disease activity by a Bruton’s tyrosine kinase (BTK) inhibitor, the first phase III trial in patients with neuromyelitis optica spectrum disorder (NMOSD), and the first multi-arm trial in secondary progressive MS (SPMS).

BTK inhibitors suppress the activation of B cells and macrophages, and their therapeutic potential is currently being explored in a range of autoimmune disorders. At ECTRIMS 2018, Xavier Montalban presented data from a phase II trial of the BTK inhibitor evobrutinib in patients with relapsing–remitting MS. Compared with placebo, oral evobrutinib treatment at a dose of 75 mg, administered once or twice daily, was associated with reductions in the accrual of gadolinium-enhancing lesions in the brain and in the annualized relapse rate. The investigators concluded that the drug warrants further evaluation in larger trials.

Takashi Namamura reported on the SAkuraSky study, a phase III trial of the anti-IL-6 receptor monoclonal antibody satralizumab in patients with NMOSD. In comparison with placebo, the drug reduced the relapse rate by 62% across the entire cohort and by 79% in a subset of patients who were seropositive for anti-aquaporin-4 antibodies. SAkuraSky is the first phase III trial to be conducted in patients with NMOSD, and the results provide validation of the IL-6 receptor as a therapeutic target in this condition.

Jeremy Chataway described an innovative multi-arm trial that was designed to test potential neuroprotective therapies in patients with SPMS. The MS-SMART trial tested three oral drugs — amiloride, fluoxetine and riluzole — against placebo. Each of the four treatment arms consisted of 110 patients with SPMS, and the primary outcome measure was a reduction in brain atrophy. Unfortunately, none of the drugs met this end point; in fact, the patients who received fluoxetine initially showed acceleration of atrophy. Nevertheless, Chataway concluded that the study design lays down a template for future work.

“While these results are disappointing, well-controlled trials such as the MS-SMART trial will help inform new approaches for future studies aimed at treating progressive forms of MS,” commented Alan Thompson, Chair of the Scientific Steering Committee of the International Progressive MS Alliance. “Lessons from this study and others will inform the Alliance’s research priorities and those of other international research funders such as the UK MS Society and National MS Society.”