European Committee for Treatment and Research in MS (ECTRIMS) 31st Congress – Barcelona, Spain, October 7-10, 2015 – The Late Breaking session at ECTRIMS 2015 was especially interesting this year as new data were presented on several novel MS treatments.
The most highly anticipated were the results from the phase III ORATORIO trial of ocrelizumab in primary-progressive MS (Montalban and colleagues. ECTRIMS 2015; abstract LB228). The study randomized 725 patients to ocrelizumab 600 mg q24weeks (two 300 mg infusions two weeks apart) or placebo for at least 120 weeks. The primary endpoint was the time to sustained disability progression on EDSS confirmed at 12 weeks. Overall, there was a significant 24% reduction in 12-week disability progression with ocrelizumab; and a 25% reduction of disability confirmed at 24 weeks. There was also a 29% difference in timed 25-foot walk favouring ocrelizumab. T2 lesion volume declined -3.45% with ocrelizumab compared to an increase of 7.4% with placebo. The most common adverse effect with ocrelizumab was infusion reactions, which occurred in 28% of subjects. Upper respiratory tract infections were similar with active treatment versus placebo (6.2% vs. 5.9%).
It was noted that ORATORIO is the first trial to demonstrate a significant benefit in PPMS. However, in the failed OLYMPUS trial of rituximab in PPMS, a subgroup analysis showed a significant reduction in time to confirmed disability progression in younger patients (aged < 51 years) and those with Gd-enhancing lesions (Hawker and colleagues. Ann Neurol 2009;66:460-471). It may be that the positive results seen in ORATORIO were due in part to the study’s inclusion criteria (age < 55 years, EDSS score 3.0-6.5, < 10 years from onset of MS symptoms), which may have selected the subgroups seen in OLYMPUS to be more likely to respond to a B cell-directed therapy. This issue should be clarified once the full study results are published.
A Canadian multicentre phase II study of minocycline 100 mg BID in patients with clinically isolated syndrome (CIS) reported a significant reduction in the proportion of patients converting to MS at one year versus placebo (41.7% vs. 66.8%) (Metz et al. ECTRIMS 2015; abstract LB227). The relative risk reduction was 37.6%. These results were comparable to those of previous CIS studies (BENEFIT, CHAMPS, PRECISE, REFLEX, TOPIC), in which risk reductions ranged from 43-52% over two years (for a recent review of CIS trials see Freedman et al. Mult Scler Relat Disord 2014;3:147-155; free full text at www.msard-journal.com/article/S2211-0348(13)00085-0/pdf). A pilot study of minocycline in MS (Zhang et al. Can J Neurol Sci 2008;35:185-191), and as add-on therapy to glatiramer acetate (Metz et al. Mult Scler 2009;15:1183-1194) have previously reported some benefits with the antibiotic, most notably in reducing inflammatory activity on MRI.
Biotin is part of the B complex group of vitamins and is often referred to as vitamin H (for Haar und Haut, or hair and skin), but a recent study suggested that its benefits may extend beyond the scalp. A pilot study in France administered high-dose biotin (100-300 mg/day) to 23 consecutive patients with primary- or secondary-progressive MS for up to 36 months (Sedel et al. Mult Scler Relat Disord 2015;4:159-169). Improvements were seen in visual evoked potentials in two patients, and 16 of 18 patients with spinal cord involvement were rated as improved.
The group has now reported the results of a study of high-dose biotin (MD1003) in SPMS/PPMS patients without baseline inflammatory activity (Tourbah et al. ECTRIMS 2015; abstract LB223). A total of 154 patients were randomized to MD1003 100 mg tid or placebo for one year. Overall, 13 of 103 patients in the MD1003 group (12.62% vs. 0% with placebo) met the primary endpoint of improvement from baseline in EDSS score or timed 25-foot walk at nine months and confirmed at 12 months. The mean change in EDSS score was -0.03 with MD1003 compared to +0.14 with placebo; this difference was significant. The authors noted that clinical benefits were more pronounced in SPMS patients compared to the PPMS group.