Selected highlights from the American Academy of Neurology annual meeting, Boston, MA, 22-27 April 2023.
COVID-19 infections with ocrelizumab
Postpartum relapse and DMTs
NMOSD frequently misdiagnosed
sNfL after menopause
Pregnancy risks with fingolimod
Phase II study of stem-cell therapy in PMS
Low rate of ocrelizumab failure
DMT non-starters common in California
CONGRESS HIGHLIGHTS – WEDNESDAY EDITION
The impaired vaccine response in ocrelizumab-treated patients is well-documented. New data show that following three vaccine doses against the omicron variant, most MS patients (59.3%) receiving ocrelizumab developed a breakthrough CoV2 infection (Novak et al. AAN 2023;P12.005). All infections were mild, suggesting some benefit from vaccination. Patients developing an infection had lower antibody levels compared to those who did not develop an infection (mean 26.5 vs. 54.4 BAU/mL). The study was conducted at MS clinics in California and Denmark.
A health claims database analysis (N=944, mean age 32.4 years) found that the risk of postpartum relapse was two-fold higher in patients who did not restart a DMT although the absolute rate was relatively low (Bove et al. AAN 2023;P9.002). The proportion of patients who relapsed was 8.7% prior to pregnancy and declined to 1.2% in the first trimester, 0.9% in the second trimester and 1.1% in the third trimester. The proportion who relapsed in the postpartum period was 5.2% for those resuming a DMT versus 10.9% for those who remained off therapy. The proportion relapsing was higher in months 0-3 postpartum vs. months 4-6 (6.5% vs. 5.4%).
A U.S. database analysis has reported that 44% of all patients with neuromyelitis optica spectrum disorder (NMOSD) were previously misdiagnosed as having MS (Wong et al. AAN 2023;P13.004). A total of 7768 NMOSD patients were identified in the database; mean age was 49.1 years and 75% were female. About 25% of misdiagnosed NMO patients (11% of total cohort) were started on a disease-modifying therapy. Data were collected in the period 2008 to 2022 and aquaporin-4 (AQP4-IgG) antibody testing may not have been available or routinely used during part of the observation period.
Serum neurofilament-light chain levels appear to increase after menopause, according to a UCSF longitudinal study of 186 postmenopausal women with MS (Silverman et al. AAN 2023; S9.009). Median age at menopause was 52 years; median duration of MS was 15 years; median EDSS score was 3.0. The accumulation of sNfL (slope difference -0.851) and MSFC worsening (slope difference 0.074) indicated increased neuroaxonal damage and functional decline after menopause. Prior studies have reported symptom worsening after menopause. However, there are conflicting findings as to the rate of disability progression worsening after menopause (Midaglia et al. Mult Scler 2022;28:173-182).
An analysis of pregnancy outcomes after DMT exposure reported that the highest risk of major congenital abnormalities was seen with fingolimod (Bast et al. AAN 2023;N2.003). The German MS and Pregnancy Registry study analysed 3363 pregnancies with and without DMT exposure. The rate of spontaneous abortion (8.5% vs. 6.3% in controls) and major congenital abnormalities (3.6% vs. 2.6%) was higher with any DMT exposure. The rate of major congenital abnormalities was 5.9% with fingolimod. In addition, fingolimod exposure, high-dose corticosteroid use and DMT exposure after the first trimester were associated with a lower birth weight.
Several years ago, a group in New York reported on the potential benefit of intrathecal administration of neural progenitor mesenchymal stem cells (MSC-NP) in progressive MS (Harris et al. EBioMedicine 2018;29:23-30). Intrathecal administration was associated with improved outcomes, according to the results of a later meta-analysis (Zhou et al. Stem Cells Int 2019;2019:8536785). The New York researchers have now completed a phase II study. Fifty-four PMS patients were stratified by EDSS score and phenotype (SPMS, PPMS) and randomized to autologous MSC-NP or placebo (Roche et al. AAN 2023;S16.005). Patients received six injections every two months followed by a one-year crossover period. No benefit was seen with respect to EDSS score, T25FW or 9-Hole Peg Test. MSC-NP was associated with improvements in the six-minute walk test. In addition, 50% of SPMS patients exhibited improved muscle strength vs. 33% of patients receiving placebo, suggesting a modest benefit of the procedure in a subgroup of patients. A prior study in active PMS reported a significant improvement in the NEDA rate with intrathecal MSC-NP vs. placebo (58.6% vs. 9.7%) (Petrou et al. Brain 2020;143:3574-3588).
A University of Ottawa study has reported that B cell counts were unchanged in 1.7% of MS patients receiving ocrelizumab (Saldivar et al. AAN 2023;P7.006). Ocrelizumab is a humanized monoclonal antibody (rituximab is chimeric, ofatumumab is a fully human MAb), suggesting that a proportion of ocrelizumab-treated patients will develop neutralizing antibodies. In the Ottawa cohort, 4 of 224 patients had normal CD19+ counts after ocrelizumab infusion. All non-responders were males with RRMS. The authors suggested that testing for neutralizing antibodies may be prudent in ocrelizumab-treated patients with clinical or radiological disease activity.
A U.S. claims database analysis (n=2024) found that one-third of people newly-diagnosed with MS did not start a disease-modifying therapy in the first year (Jordan et al. AAN 2023;S3.017). About one-third of patients started treatment within 60 days of an MS diagnosis. The most common treatments were glatiramer acetate, dimethyl fumarate and ocrelizumab. The median time to treatment start was 35 days for GA, 47 days for DMF and 79 days for ocrelizumab.