Controversies with revised 2017 McDonald criteria
Aggressive treatment is more effective, but…
Dimethyl fumarate – long-term data
Examining autoimmunity with alemtuzumab
2-minute walk more sensitive than T25FW

Controversies with revised 2017 McDonald criteria
The 2017 revisions to the McDonald criteria introduced three important changes: OCBs could be substituted for dissemination in time (DIT) to arrive at a diagnosis of MS; asymptomatic Gd+ lesions could be used when determining dissemination in space and time; and cortical lesions could be used to support dissemination in space (DIS) (Thompson et al. Lancet Neurol 2018;17:162-73).

Brownlee and colleagues retrospectively applied the 2010 and 2017 revisions to its database of 154 CIS patients who had been followed for 15 years (Brownlee et al. ECTRIMS 2018; abstract 1410). The 2017 DIS criteria were more sensitive (88% vs. 85%) and the specificity was the same (73%); the DIT criteria were more sensitive (94% vs. 87%) but less specific (72% vs. 73%). Taken together, the 2017 criteria were more accurate than the 2010 criteria (83% vs. 79%).

The new criteria can enable an earlier diagnosis of MS (Gaetani et al. J Neurol 2018; epublished September 8, 2018), but two cautionary notes have been sounded. One study recently reported that 33% of patients diagnosed with the 2017 criteria did not experience a second attack during the 5-year follow-up (vs. 23% with the 2010 criteria) (van der Vuurst de Vries et al. JAMA Neurol 2018; epublished August 6, 2018). The second concern is the medicolegal implications of retrospectively applying the new criteria to CIS patients (Giovannoni et al. ECTRIMS 2018; abstract P653). In a recent survey of MS specialists in the UK, 51% said they were likely to offer their CIS patients a lumbar puncture to change their diagnosis to MS. However, only 40% said they felt ethically obliged to apply the new criteria, and 32% expressed concerns about the medicolegal ramifications. Most clinicians (70%) said that applying the new criteria retrospectively had socioeconomic consequences for patients previously diagnosed with CIS.
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Aggressive treatment is more effective, but…
Two studies at ECTRIMS examined outcomes in MS patients treated with higher-efficacy DMDs. The MSBase group analysed long-term disability outcomes with higher-efficacy therapy agents that were started either earlier (0-2 years after disease onset) or later (>4 years) in the clinical course (n=748) (He et al. ECTRIMS 2018; abstract P919). Those starting on a higher-efficacy therapy earlier experienced worse EDSS progression in the first two years, but had lower mean EDSS scores than the later group at 6 years (2.5 vs. 3.4). Differences remained significant up to 10 years after disease onset.

A Danish MS registry study examined patients (n=807) who relapsed on a moderately-effective DMD who were switched to another moderately-effective agent or escalated to a higher-efficacy drug (Chalmer et al. ECTRIMS 2018; abstract 263). At 3 years, there was a 39% lower risk of a first relapse with a higher-efficacy agent. ARR was 0.21 with the higher efficacy DMD versus 0.34 with a moderately-effective agent. Higher-efficacy therapy was also associated with a 13% lower risk of EDSS worsening by 1 point.

A survey of U.S. neurologists found that a majority (52%) favoured a treatment-optimization approach using a higher-efficacy agent rather than a treatment-escalation approach (Naismith et al. ECTRIMS 2018; abstract P868). However, a chart review found that higher-efficacy agents were used in only 23.3% of cases. Early use of a higher-efficacy therapy was similar in neurologists who advocated higher-efficacy therapies compared to those favouring an escalation approach (24.8% vs. 18.9%, NS). Early use of higher-efficacy DMDs did not differ by years in practice, practice setting, academic affiliation, or MS center affiliation.
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Dimethyl fumarate – long-term data
Relapse rates remain low and accumulation of disability is uncommon in newly-diagnosed patients on dimethyl fumarate for 9 years, according to data from the long-term follow-up of ENDORSE (Gold et al. ECTRIMS 2018; abstract P920). ARR was 0.14, and the proportion of patients with EDSS ≤3.5 was 93% at Year 9. There was a 64% reduction in the relapse rate in the year following a switch from placebo to DMF (ARR 0.09 in years 3-9). A total of 50% in the continuous DMF group remained on therapy after a median 8.6 years. The discontinuation rate due to MS was 11%.
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Examining autoimmunity with alemtuzumab
There has been much speculation about the cause(s) of autoimmune adverse events in a subset of patients treated with alemtuzumab; suggestions have included B cell hyperrepopulation, and B cell repopulation prior to Treg reconstitution. Lymphocyte kinetics have now been examined in alemtuzumab-treated patients with or without an autoimmune adverse event over a 6-year follow-up period (Wiendl et al. ECTRIMS 2018; abstract P880). The T cell subsets examined were CD3+, CD4+ and CD8+ (including naïve, memory and regulatory T cells); the B cell subset was CD19+ (including immature, mature and memory B cells). The CD19+/Treg ratio was also examined. No differences in lymphocyte depletion or repopulation were seen in patients with and without autoimmune events. The authors concluded that differences in lymphocyte depletion or repopulation kinetics are not predictive of the occurrence of autoimmune AEs in alemtuzumab-treated patients.

A separate study examined whether autoimmune antibodies were predictive of autoimmunity during treatment with alemtuzumab (Sandgren et al. ECTRIMS 2018; abstract P934). The autoantibodies were thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), glutamic acid decarboxylase antibodies (GADAb), islet cell antibodies (ICA) and anti-glomerular basement membrane antibodies (GBMAb). A total of 65% of patients who developed an autoimmune thyroid disorder had positive TgAb and TPOAb at baseline. Three of 51 patients (5.9%) had positive thyroid autoantibodies at baseline, and all subsequently developed an autoimmune thyroid disorder.
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2-minute walk more sensitive than T25FW
The RESERVE project reports that the 2-minute walk (2MW), which requires that patients walk as quickly as they can for two minutes, is more sensitive to subtle gait changes than the Timed 25-Foot Walk (Kurz et al. ECTRIMS 2018; abstract P707). A shorter 2MW distance, but not a longer T25FW, was associated with higher T2 lesion volume. Both measures discriminated between patient-reported mild vs. moderate gait problems, but only 2MW distinguished between minimal vs. mild gait disturbances.
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