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 3 of ECTRIMS 2022.
October 28 Edition
October 27 Edition
COVID vaccine response with ofatumumab
COVID boosters in DMT-treated patients
MRI of the beholder
Treatment discontinuation in MS
Sedentary lifestyle common in MS
Treatment decision-making
Clinical tip of the day
CONGRESS HIGHLIGHTS – SATURDAY EDITION
COVID vaccine response with ofatumumab
The KYRIOS study examined COVID vaccine response during treatment with ofatumumab (Ziemssen et al. ECTRIMS 2022; P711). In the interim analysis, all patients who were vaccinated mounted an immune response (humoral and cellular) as early as one week after ofatumumab injection. Most patients also showed a response to a booster vaccine although neutralizing antibody titres were lower than those in controls.
A pilot study examined the response to COVID vaccination in 26 patients receiving ofatumumab (Hendin et al. ECTRIMS 2022; P345). Assays were performed >14 days after the second or third vaccination. Mean duration of ofatumumab treatment was 7.9 months. Overall, 54% mounted an immune response in the first assay; response to a booster injection was 70% (86% if aged <50 years). The vaccine response was less robust in older patients and those who had previously received ocrelizumab.
COVID boosters in DMT-treated patients
A study examined the response to a booster injection in 79 MS patients currently on a DMT who were seronegative after receiving the first two vaccinations (Upcott et al. ECTRIMS 2022; P343). In total, 34% seroconverted after the booster injection; seroconversion rates were 17% with ocrelizumab, 47% for fingolimod and 100% for other DMTs. A T cell response was more common after the third (65%) or fourth (68%) vaccination but was absent in the fingolimod group. Overall, 75% of previous vaccine non-responders showed some immune response to a booster injection.
Also noteworthy was an Italian study of COVID severity following a booster injection in 232 MS patients during treatment with natalizumab, ocrelizumab or fingolimod (Gallo et al. ECTRIMS 2022; P560). Fever, cough, dyspnea, longer COVID symptom duration and need for supplemental oxygen were more common in the ocrelizumab vs. natalizumab group. Fever, cough and dyspnea were also more common with fingolimod vs. natalizumab. While COVID symptoms were generally more severe in patients receiving ocrelizumab or fingolimod, there was no difference among the treatment groups with respect to hospitalizations, use of steroids or mortality.
MRI of the beholder
A new study asked two radiologists to interpret MRIs obtained from MS patients with varying levels of disease activity (Keshavan et al. ECTRIMS 2022; P224). The radiologists agreed about the presence of Gd-enhancing lesions, but agreement was only fair for lesion counts (infratentorial, supratentorial), new lesions and lesion burden. Agreement was poorest for the presence of expanding lesions and brain atrophy.
Treatment discontinuation in MS
A two-centre study in France investigated whether DMT discontinuation was associated with an increase in inflammatory disease activity (Chappuis et al. ECTRIMS 2022; EP1163). The study looked at 49 patients aged >45 years treated with a high- or moderate-efficacy DMT for at least six months. The relapse risk in the year after discontinuation was 6% for the group on a moderate-efficacy DMTs, 9% for those on fingolimod and 43% for those on natalizumab. The risk of relapse peaked in the first three months after stopping fingolimod or natalizumab.
A five-year follow-up study in the Netherlands investigated disease reactivation in 130 patients (mean age 45 years) who stopped taking a platform DMT (Coerver et al. ECTRIMS 2022; P302). Overall, 47.7% of patients had new MRI activity and 30.8% experienced a relapse after discontinuing treatment; 22.3% restarted treatment after a median 17 months. Patients aged 45-55 years had a lower risk of MRI activity (odds ratio 0.287) and relapses (OR 0.439) compared to younger patients
Treatment discontinuation is also being examined in the DISCOMS trial, which reported that stopping treatment in stable patients aged >55 years was not non-inferior to continuing treatment. At 22 months, patients who stopped typically developed 1-2 new lesions without relapses and worsening disability. An extension study is ongoing (Corboy J. ECTRIMS 2022; EP1089). Patients will have one visit and brain MRI at 30-54 months after the initial enrollment. The primary endpoint will be time to relapse or new MRI activity. Thus far, most participants are receiving an injectable therapy as their DMT.
Sedentary lifestyle common in MS
A survey of MS patients in Saskatchewan reported that 58% were insufficiently active to achieve health benefits from exercise (Knox et al. ECTRIMS 2022; EP0845). Patients who never started a DMT (28% of respondents) were more likely to be sufficiently active than those on treatment. Meanwhile, a European pilot study of a structured exercise intervention found that while MS patients and healthy controls trained at a similar intensity level, MS patients compensated for the exercise by increasing their amount of sedentary behaviour on non-exercise days (Nieste et al. ECTRIMS 2022; P791). As a result, the MS group obtained less benefit from the exercise regimen.
Treatment decision-making
A U.S. survey of 145 neurologists and advanced practice clinicians investigated the relative importance of factors influencing treatment choice (Bandari et al. ECTRIMS 2022; P384). Respondents stated that safety was most important, followed by relapse reduction and slowing of disability progression. However, an accompanying discrete-choice questionnaire identified additional factors. In selecting a DMT, dose frequency was considered more important than efficacy, the need for dose titration was as important as safety, and volume of patient calls was as important as GI tolerability. The authors concluded that logistical considerations are as important as clinical factors when choosing therapy.
Clinical tip of the day
Urine dipstick testing prior to ocrelizumab initiation to identify current infection has a low yield and will delay the time to treatment infusion (Dorsey-Campbell et al. ECTRIMS 2022; P740). Concerns have been raised about the risk of urosepsis if ocrelizumab is initiated in a patient with a current UTI. The three-year study examined 353 urinalysis results in 119 MS patients. Overall, 85% of dipstick tests were negative. Only one positive test resulted in a diagnosis of a UTI requiring antibiotics. The authors noted that waiting for blood test results following a positive dipstick test resulted in a delay in initiating ocrelizumab.
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