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 3 of ECTRIMS 2021.
CONGRESS HIGHLIGHTS – FRIDAY EDITION
COVID-19 vaccine response and DMTs
The New York State MS Consortium examined the humoral response to COVID-19 vaccination in 497 MS patients receiving an mRNA vaccine or the AstraZeneca vaccine (Weinstock-Guttman et al. ECTRIMS 2021; abstract P630). The humoral response was determined by measuring either IgG antibodies or anti-spike IgGs. The response rates were 75.6% (anti-spike IgG) and 33.3% (nonspecific IgGs). The seroconversion rate was higher in patients receiving dimethyl fumarate (100%), glatiramer acetate (100%), natalizumab (100%) and interferon-beta (91.0%); the rate was 94.2% in untreated patients. Seroconversion rates were lower among those receiving teriflunomide (80.0%), S1PR modulators (26.3%) or anti-CD20 agents (22.6%). Zero of 3 patients switched from ocrelizumab to cladribine seroconverted. A total of 1.1% of MS patients developed COVID after being fully vaccinated.
An Italian study looked at the humoral response at 7 days after the second COVID vaccination in 80 MS patients and 51 healthy controls (Capuano et al. ECTRIMS 2021; abstract P651). The assay used detected anti-spike IgG, with 33.8 binding antibody units (BAU) used as the cut-off. Anti-CoV-2 antibodies were detected in all healthy controls and 100% of patients on natalizumab, 54.8% of patients on ocrelizumab and 40.0% on fingolimod. The antibody response was significantly blunted in patients receiving ocrelizumab or fingolimod (median BAU 59.8 and 21.5, respectively) compared to healthy controls (BAU 1860) or natalizumab patients (BAU 3015). The likelihood of seroconversion was correlated with time since last ocrelizumab infusion and duration of fingolimod exposure. A reduction in humoral immunity with rituximab and fingolimod was also reported in the Norwegian NEVROVAX study (Konig et al. ECTRIMS 2021; abstract P650).
COVID-19 outcomes with ofatumumab
An analysis of the ongoing ALITHIOS extension study (n=1703) identified 139 (8.2%) confirmed or suspected cases of COVID-19 during treatment with ofatumumab (Cross et al. ECTRIMS 2021; abstract P982). The mean time on treatment was 2.2 years. Overall, 92.8% of cases were non-serious and 7.2% required hospitalization. There was one death (0.7%). Treatment was interrupted in 22 patients. Mean time to COVID-19 recovery was 19.7 days. For all cases, serum IgG levels were above the lower limit of normal (5.65 g/L) before or during COVID-19 infection. A separate analysis of three patients reported that there was T cell immunity during ofatumumab treatment.
Delayed dosing effective during pandemic
Uncertainty regarding the safety of high-efficacy infusion drugs during the pandemic prompted some clinicians to delay dosing. A single-centre analysis in the US examined the efficacy of ocrelizumab when six-monthly infusions were delayed a mean of 8 weeks (Smoot et al. ECTRIMS 2021; abstract P639). Following the delay, there were two suspected relapses but no patient demonstrated an enhancing lesion. The authors concluded that less frequent dosing of ocrelizumab may be as effective as the usual dosing. A UK study of ocrelizumab reported no increase in disease activity with extended-interval dosing (Allen et al. ECTRIMS 2021; abstract P826). Treatment was typically administered every 7-9 months, although some were dosed less often than every 9 months. Overall, 2% experienced a relapse and 8% had new MRI lesions.
A study in Portugal examined data for 90 clinically stable patients on natalizumab switched to extended-interval dosing (q6weeks) during the pandemic (Bernardes et al. ECTRIMS 2021; abstract P787). During the one-year follow-up, one patient experienced a relapse and six patients were switched back to standard dosing because of symptoms (e.g. fatigue, constipation) that were considered to be part of a wearing-off phenomenon.
No evidence of disease activity (NEDA)
A UK study analysed baseline predictors of NEDA in RRMS patients on treatment with dimethyl fumarate (n=670) (Al-Araji et al. ECTRIMS 2021; abstract P807). The mean age of patients was 40.5 years; the mean disease duration was 8.6 years. NEDA was defined as no relapses, new MRI activity or disability worsening. Over the one-year observation period, 71% of DMF-treated patients achieved NEDA. NEDA predictors at the start of treatment were a lower EDSS score, fewer baseline MRI lesions and fewer relapses in the prior 12 months.
A meta-analysis of 29 studies (n=10,528) examined the value of NEDA in predicting long-term disability in treated patients with MS (Rotstein et al. ECTRIMS 2021; abstract P796). The mean duration of follow-up was 6.3 years (range 4-16). The positive predictive value of NEDA for no EDSS worsening was >90% for platform and high-efficacy DMTs. However, the absence of NEDA was not highly predictive of EDSS worsening. The authors noted that since few patients with disease activity developed worsening disability, additional criteria may be needed to guide treatment switches. A previous analysis of the CLIMB database reported an overall NEDA rate of 46% at one year, however, <10% maintained NEDA at 7 years (Rotstein et al. JAMA Neurol 2015;72:152-158). The positive predictive value of NEDA for progression in that study was 78.3%.
Clinical tip of the day
Canadian neurologists working at MS clinics believe that physical activity is important but they often fail to discuss it with their patients, according to a new survey (Thebault et al. ECTRIMS 2021; abstract P879). Neurologists asked patients about their physical activity only 70% of the time and promoted its value in 65% of cases. Most neurologists said that there was insufficient evidence to support the role of physical activity as an adjunct to DMTs. About one-half said they were unsure about what resources were available in the community.