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Oral DMT use
Disease reactivation and miscarriage
French Canadians
Biomarkers
Concussion and MS

Increasing use of oral DMTs
A retrospective study obtained health administrative data to analyse the use of oral disease-modifying therapies in British Columbia, Canada, for the period 2011-2015 (Setayeshgar et al. ECTRIMS 2017; abstract P346). The oral DMTs introduced during this period were fingolimod, dimethyl fumarate and teriflunomide.

Among 12,272 MS patients, there were 1,019 new users (8.3%) of at least one oral DMT during the study period. Fingolimod use increased from 2.4 to 19.4 per 1000 MS patients; DMF use increased from 6.2 to 39.5/1000; and teriflunomide use increased from 4.2 to 16.0/1000. Use of injectable DMTs declined 31% during this same period. However, a majority of patients continued to be treated with an injectable DMT in 2015. Patients aged 45 years or younger were more likely to be current DMT users, and were more likely to fill a prescription for an oral DMT.
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Risk of disease reactivation after miscarriage
A retrospective analysis of data from four Italian MS centres found that there is an increased risk of disease reactivation following miscarriage in women with RRMS (Landi et al. ECTRIMS 2017; abstract P326).

Data were obtained for 88 miscarriages in 69 women during the period 1983-2016. Mean age at miscarriage was 34 years, and occurred after a mean of 9.6 weeks after the estimated conception date. A total of 62 of 88 miscarriages (70.5%) occurred during treatment with a DMT. Following miscarriage, there was no change in annualized relapse rates (pre: 0.47; post: 0.38). However, the mean number of gadolinium-enhancing lesions significantly increased after miscarriage (from 0.36 to 0.76). Gd+ lesion number was higher in patients with a shorter duration of pregnancy prior to miscarriage, and patients with a higher number of Gd+ lesions prior to pregnancy.
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Mortality among French Canadians with MS
The CHUM MS clinic in Montreal examined mortality data from a cohort of 3771 MS patients over a median follow-up period of 13.7 years (Rousseau et al. ECTRIMS 2017; abstract P341). A total of 482 patients (12.8%) had died by the end of the study period.

The overall mortality rate was 8.7 per 1000-years. (The overall age-standardized mortality rate in Canada in 2013 was 4.8/1000 population) (Statistics Canada; www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/hlth86b-eng.htm). The mortality rate was higher in men (11.6 vs. 7.6/1000 PY in women). Disease course had a significant impact on mortality rates: 5.5/1000 PY in patients with clinically isolated syndrome; 7.2/1000 PY in RRMS; 18.2/1000 PY in SPMS; and 19.1/1000 PY in PPMS.

A subgroup analysis also determined that age of onset influenced mortality. Mortality rates were lower in patients diagnosed at a younger age (4.3/1000 PY if age 20-40 years at diagnosis) compared to an older age (11.5/1000 PY if older than 40 years). These results support previous reports of higher mortality rates in patients with MS.
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NfL examined as potential biomarker
Numerous biomarkers have been proposed for predicting conversion from CIS: OCBs, kappa free-light chain, IgG against neurotropic viruses, chitinase-3-like protein-1, soluble CD27, and neurofilament light chain (NfL) (Thouvenot et al. ECTRIMS 2017; abstract 99). NfL has also been suggested as a biomarker of disability progression and time to SPMS.

Two studies have now examined the utility of NfL as a marker of treatment success. The first examined serum NfL levels from baseline to week 48 in the ADVANCE phase III trial of peg-interferon-beta-1a (Calabresi et al. ECTRIMS 2017; abstract 102). Baseline serum NfL levels were significantly associated with the number of Gd+ lesions and T2 lesion volume at baseline, and the number of T2 lesions and percent brain volume change (PBVC) at the end of year 2. Treatment with peg-IFN-beta-1a resulted in a significant decrease in NfL levels compared to placebo (55% vs. 26%). In a subgroup analysis of placebo patients with or without evidence of disease activity (EDA vs. NEDA), NfL levels remained consistently low in the NEDA group; NfL levels were higher and more variable at all time points in the EDA group.

A separate study examined serum NfL levels in 98 RRMS and 48 progressive MS patients (Novakova et al. ECTRIMS 2017; abstract 75). Median serum NfL levels were unchanged in untreated patients who either remained untreated (40.7 vs. 37.1 ng/L) or started treatment with a first-line DMT (20.6 vs 25.5 ng/L); or treated patients who switched from one first-line DMT to another (17.3 vs. 16.7 ng/L). In contrast, median NfL levels decreased significantly in untreated patients who started on a second-line DMT (22.7 vs. 18.5 ng/L); and those who escalated from a first- to a second-line therapy (17.9 ng/L vs. 12.6 ng/L). NfL levels were low and stable in patients switching from one second-line therapy to another (14.9 vs. 13.7 ng/L).
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Concussion – an MS risk factor?
An analysis of the Swedish Patient and MS Registries has reported that concussion during adolescence increases the risk of developing MS (Olsson et al. ECTRIMS 2017; abstract P339). All patients with an MS diagnosis up until 2012 (n=7292) were matched with 10 people without MS (total n=80,212). Concussion was identified for individuals up to age 20 in the Patient Registry.

One concussion during adolescence was associated with a significantly elevated risk of developing MS (adjusted odds ratio 1.22 vs. no concussions). MS risk was higher in individuals with a history of multiple concussions (adjusted OR 2.33 vs. no concussions). The authors speculated that during adolescence, inflammation resulting from head trauma may initiate an autoimmune response in the CNS.
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