37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis – October 13-15, 2021
The following summarizes some of the highlights from Day 2 of ECTRIMS 2021.
CONGRESS HIGHLIGHTS – THURSDAY EDITION
Does COVID-19 vaccination trigger MS relapses?
There are conflicting data on whether COVID-19 vaccination can trigger an MS relapse. A single-centre study in the US reported no relapses among 102 consecutive patients vaccinated with the Pfizer or Moderna vaccines (Chou et al. ECTRIMS 2021; abstract P133). However, there were 6 reported cases (5.9%) of pseudorelapses, which may have been attributable in part to the higher rate of fever post-vaccination among MS patients compared to the general population (25% vs. 16%). A study in Israel found that 1.5% of MS patients experienced a relapse after the first vaccine dose; the relapse incidence was 3.1% within a median of 41 days after the second vaccine dose (Dreyer-Alster et al. ECTRIMS 2021; abstract P187). The rate of acute relapses was comparable in vaccinated and non-vaccinated patients.
The Kaiser Permanente database has reported a total of five cases of relapse (4 myelitis, 1 brainstem event) occurring within 2 weeks of receiving an mRNA vaccine during the period February-May 2021 (Marcus J. ECTRIMS 2021; abstract P371). All subjects had MRI lesions, including three with enhancing lesions. In addition, the Oxford group has documented 12 NMO-like acute demyelinating events in the period February-May 2021 (Camera et al. ECTRIMS 2021; abstract P894). Onset symptoms were transverse myelitis (66.7%), optic neuritis (33.3%) and brainstem/cerebellar/cranial nerve syndromes (33.3%). Ten of 12 cases occurred following the AstraZeneca vaccine; 2 cases occurred after the Pfizer vaccine. There was one death in a 44-year-old male who developed dyspnea, quadriplegia and respiratory failure after receiving the AstraZeneca vaccine; MRI lesions were present in the cerebral hemispheres, brainstem and spinal cord. To date, 66 cases of acute demyelinating events have been reported following COVID vaccination but it is not known if this is higher than the background rate.
Older age at MS onset
Despite the perception that MS is diagnosed earlier now, contemporary cohorts of MS patients are older at diagnosis, according to a retrospective database analysis in Spain (n=1622) (Romero-Pinel et al. ECTRIMS 2021; abstract P150). The study found that the mean age at diagnosis was 23.79 years in the 1970s, 27.86 years in the 1980s, 30.07 years in the 1990s, 32.12 years in 200-2009, and 34.28 years in 2010-2019. The same phenomenon was seen when patients with early-onset (<18 years) or late-onset (>50 years) MS were excluded. This trend to later diagnosis or later onset is also evident in contemporary drug trials, which typically recruit newly-diagnosed patients in their late 30s.
Treatment outcomes with siponimod
A post-hoc analysis of the EXPAND trial determined that 78% of patients responded to siponimod on at least one measure of disability progression (Bovis et al. ECTRIMS 2021; abstract P113). There was a significant effect on time to confirmed progression with siponimod on EDSS (hazard ratio 0.79) and cognition as assessed by SDMT (HR 0.75). Group-level response on the 9-Hole Peg Test and Timed 25-Foot Walk was not significant, however, individual patients did show improvement on one or more of these measures. The authors speculated that patients may respond differently to treatment depending on the underlying pathophysiology of their MS.
A separate analysis from EXPAND reported that siponimod had comparable efficacy in younger and older SPMS patients with active disease (Hua et al. ECTRIMS 2021; abstract P637). In the subgroup aged <50 years, siponimod reduced the risk of 6-month confirmed disability progression by 38%; in patients aged >50 years, the risk reduction with siponimod was 37%. Rates of adverse events were similar for the two age groups. The rate of adverse events leading to discontinuation was slightly higher in the older age group (6.8% vs. 5.9%).
NfL increase may predict relapse
A 1-year Canadian study (n=58) has found that increasing serum neurofilament-light (sNfL) may be predictive of future relapses (Thebault et al. ECTRIMS 2021; abstract P569). Patients who relapsed had higher baseline sNfL levels compared to non-relapsing patients (20.9 vs. 11.4 pg/mL). A two-fold higher baseline level (20 vs. 10 pg/mL) was associated with a 2.3-fold increased risk of relapse in the subsequent year. Moreover, there was a 1.5-fold increased risk of relapse in patients demonstrating a two-fold increase in sNfL over time, most noticeably in patients with lower baseline sNfL levels. Previous studies have reported that baseline sNfL levels are predictive of new MRI lesions (Calabresi et al. Mult Scler 2021;27:1497-1505); and that sNfL levels increase during relapse periods (Huss et al. Biomedicines 2020;8:312). A caveat, however, is that an estimated 33-50% MS patients (as well as healthy controls) will exhibit substantial changes from baseline (>20%) in sNfL due to natural variability (Bridel et al. Mult Scler Relat Disord 2021;47:102666).
Clinical tip of the day
Among MS patients who contract COVID-19, an estimated one-third will experience persistent symptoms (Garjani et al. ECTRIMS 2021; abstract P296). “Long COVID” lasted >4 weeks in 29.5%, and >12 weeks in 9.8% of MS patients. Risk factors for long COVID were higher EDSS scores and pre-COVID anxiety and depression.