38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis – October 26-28, 2022
The following summarizes some of the highlights from Day 1 of ECTRIMS 2022.
October 29 Edition
October 28 Edition
Does COVID-19 worsen MS?
Long-term DMT data
MS risk with adolescent obesity
Is vitamin D supplementation effective?
Poor vaccine response in children
Hypogammaglobulinemia with ocrelizumab
Effect of ibudilast on SELs
Clinical tip of the day
CONGRESS HIGHLIGHTS – THURSDAY EDITION
Does COVID-19 worsen MS?
There are conflicting reports on whether MS worsens following COVID-19 infection. An analysis of the Belgian National MS database of MS patients with COVID-19 (N=234) reported that mean EDSS scores worsened during the COVID infection period compared to pre-pandemic (Peeters et al. ECTRIMS 2022; P119). The mortality rate was 2.1%. In contrast, an Austrian study reported no significant difference in MS patients with COVID vs. matched controls in the proportion with relapses (8.6% vs. 7.0%) or EDSS progression (5.6% vs. 4.2%) (Bsteh et al. ECTRIMS 2022; P515). Similarly, an Italian propensity-score matched study of MS patients with and without COVID found no significant difference in NEDA rates at three months (78.3% vs 84.8%) or six months (66.2% vs 76.1%) post-COVID (Bosa et al. ECTRIMS 2022; P056). Interestingly, the only predictor of long COVID was treatment with an anti-CD20 therapy. Finally, the VaxiRIS study found that the rate of clinical conversion to CIS/MS was unchanged in RIS subjects with COVID infection or who received a COVID vaccine (Cohen et al. ECTRIMS 2022; P457).
Long-term DMT data
In the ALITHIOS extension of the ASCLEPIOS trials, a low annualized relapse rate (ARR) was maintained for up to four years with ofatumumab in the recently diagnosed/treatment naïve subgroup (Gartner et al. ECTRIMS 2022; P052). ARR was 42% lower in the continuous ofatumumab vs. teriflunomide/ofatumumab switch group. Mean EDSS was 2.30. Serious adverse events were reported in 16.2% of patients. The results extend the findings from the subgroup analysis of the core studies (Gartner et al. Mult Scler 2022;28:1562-1575).
MS risk with adolescent obesity
Overweight or obesity during childhood or adolescence increased the risk of developing MS in females (odds ratio 2.48) but not males, according to a population-based study in the Netherlands (Loonstra et al. ECTRIMS 2002; P171). There was also an earlier MS onset in overweight females who smoked before age 18 years. Curiously, overweight males had a lower EDSS score later in life than non-overweight males. After MS onset, body weight had no effect on relapse frequency or time to EDSS >6.0.
Is vitamin D supplementation effective?
The VIDAMS (Vitamin D to Ameliorate MS) study examined vitamin D add-on therapy to glatiramer acetate in RRMS patients with recent disease activity (Cassard et al. ECTRIMS 2022; P301). Subjects (N=172) were randomized to a low-dose (600 IU) or high-dose (5000 IU) daily regimen of vitamin D3 for up to 96 weeks. There was no significant difference in the proportion of patients with relapse (32% vs. 34%) or other clinical and MRI endpoints with the two regimens.
Poor vaccine response in children
A retrospective analysis found low antibody titres against hepatitis B (33%) and varicella zoster virus (25%) following vaccination in untreated pediatric-onset MS patients (Khoshnood et al. ECTRIMS 2022; P043). One-quarter had no response to either vaccine. The findings suggest a systemic immune dysfunction early in the clinical course of MS.
Hypogammaglobulinemia with ocrelizumab
A Quebec study reported that the rate of hypogammaglobulinemia in ocrelizumab-treated patients increased over time (Nobile et al. ECTRIMS 2022; P283). The study included 266 RRMS and PPMS patients followed up for a mean of two years. After six ocrelizumab infusions, the proportion with at least one hypogammaglobulinemia event was 32.8% (IgM), 4.2% (IgG) and 3.5% (IgA). All three Igs showed a significant decline with continued dosing. No association was found between hypogammaglobulinemia events and serious infection. This was also the finding of a U.S chart review (N=444) (Smoot et al. ECTRIMS 2022; P346). Infections occurred in 28% of ocrelizumab courses but were unrelated to Ig levels. Risk factors for infection were female sex and treatment duration >2 years.
A pilot study reported that hypogammaglobulinemia can be prevented with extended-interval dosing (EID) of ocrelizumab (Schuckmann et al. ECTRIMS 2022; P748). After four standard treatment cycles, the EID group received ocrelizumab according to B cell levels (dosing when CD19+ B cells >1% of peripheral blood lymphocytes), which translated to a mean time of 46 weeks between infusions. There was no loss of treatment efficacy in patients who were previously stable on the usual dosing regimen.
Effect of ibudilast on SELs
In the phase II SPRINT-MS trial, the phosphodiesterase inhibitor ibudilast was shown to reduce brain atrophy in progressive MS (Fox et al. N Engl J Med 2018;379:846-855). A subsequent analysis found that ibudilast reduced gray matter atrophy without significantly reducing new T2 or T1 lesions (Naismith et al. Neurology 2021;96:e491-e500). A new SPRINT-MS analysis now reports a 26% reduction in slowly-evolving lesion (SEL) volume (Fox et al. ECTRIMS 2022; P188). The treatment effect was similar in PPMS and SPMS.
Clinical tip of the day
MS patients are more likely to report cognitive impairment if they have significant fatigue, but not if they have depression or physical disability (Jackson et al. ECTRIMS 2022; P104). In contrast, clinicians are more likely to perceive cognitive deficits in older patients, as well as those with depression, physical disability or poor quality of life. The authors noted that these differences in perceived cognitive impairment suggest that the impact of MS on daily living may not be fully appreciated and could affect when cognitive screening is performed.
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