The American Academy of Neurology (AAN) annual meeting, scheduled for April 25-May 1, 2020, was cancelled due to the COVID-19 pandemic. The following summarizes some of the new research that would have been presented at AAN 2020.
CONGRESS HIGHLIGHTS – THURSDAY EDITION
Alemtuzumab – 9-year data
Siponimod long-term data
Stopping DMTs in inactive patients
Changing definition of SPMS
How prognostic is confirmed disability progression?
Quetiapine and remyelination
New data for solriamfetol
Alemtuzumab – 9-year data: A 9-year analysis of the CARE-MS II cohort found that 41% have not required additional therapy after the initial two-year course (Bass et al. AAN 2020; abstract P7.022). ARR was 0.19 in years 3-9. Overall, 69% had no new/enlarging T2 lesions, 89% had no Gd+ lesions and 60% had no 6-month confirmed disability progression. The cumulative incidence of thyroid adverse effects was 44%; the cumulative incidence of immune thrombocytopenia was 3.7%.
Siponimod long-term data: The EXPAND trial compared siponimod 2 mg/day with placebo in patients with SPMS (Kappos et al. Lancet 2018;391:1263-1273). In the long-term extension, there was greater long-term benefit with continuous siponimod compared to delayed siponimod (placebo/siponimod) (Kappos L. AAN 2020; abstract S40.003). The time to six-month CDP was longer with continuous siponimod versus placebo/siponimod (21.0 vs. 13.6 months), a 54% improvement. ARR was 0.054 versus 0.097 for the continuous and delayed groups, respectively. The risk of worsening SDMT score was reduced 23% with immediate versus delayed siponimod.
Stopping DMTs in inactive patients: A California study examined outcomes in 134 older patients with inactive MS who stopped their DMT (McFaul et al. AAN 2020; abstract P8.012). At the time of treatment discontinuation, mean patient age was 60.5 years, mean disease duration was 19.1 years, and mean time since last relapse was 10.7 years; 97% were being treated with an injectable DMT. Over the 5-year follow-up, 7.5% had new Gd+ or T2 lesion activity, 3.7% had a relapse and 1.5% developed mild residual deficits. Six patients (4.5%) restarted treatment due to a return in disease activity.
Changing definition of SPMS: Neurologists are changing how they diagnose SPMS, according to U.S. surveys conducted in 2018 and 2019 (Naismith et al. AAN 2020; abstract P5.007). Neurologists were more likely to rely on 6-month confirmed disability progression (25% in 2019, 16% in 2018) and increased brain atrophy (15% vs. 9%), and less likely to rely on an absence of relapses (12% vs. 24%), time since MS diagnosis (11% vs. 16%) and decreased ARR (6% vs. 11%). MS specialists tended to use 6-month CDP to identify SPMS; general neurologists were more like to rely on worsening MRI findings and decreased walking speed. MS specialists were also more likely than general neurologists to categorize an SPMS patient as having active disease (73% vs. 59%).
How prognostic is confirmed disability progression? : An analysis of the CLIMB database examined the value of confirmed disability progression (CDP) in predicting time to EDSS 6 or SPMS onset (Healy et al. AAN 2020; abstract S54.003). While CDP was associated with a shorter time to EDSS 6 in univariate analysis, models that included CDP were less predictive than those that used EDSS scores and excluded CDP. Clinical and MRI features were also more useful than CDP in predicting subsequent events.
Quetiapine and remyelination : Animal studies have suggested that quetiapine, an atypical antipsychotic that interacts with multiple neurotransmitters, has potential neuroprotective effects (reviewed in Zhornitsky et al. CNS Neurosci Ther 2013;19:737-744). However, a University of Calgary phase I study found that even low doses of quetiapine (100-150 mg/day) were poorly tolerated (Metz et al. AAN 2020; abstract P9.017). The limiting side effect was sedation.
New data for solriamfetol: Solriamfetol (Sunosi) is a dopamine/norepinephrine reuptake inhibitor that received FDA approval in 2019 for the treatment of daytime sleepiness in patients with narcolepsy or obstructive sleep apnea. A maintenance (up to 50 weeks) study of patients previously enrolled in a trial recently reported improvements in Epworth Sleepiness Scale scores, with worsening scores when subjects were randomized to placebo (Malhotra et al. Sleep 2020;43:pii: zsz220). Adverse effects included headache, nausea, anxiety and decreased appetite; 4.2% had serious adverse effects and 9.5% stopped treatment due to AEs. A separate analysis reported sustained reductions in impairments at work (29.5%) and outside of work (26.7%) (Foldvary-Schaefer et al. AAN 2020; abstract P3.004).
Clinical tip of the day: It may be useful to screen for hypogammaglobulinemia when patients receiving an anti-CD20 DMT have been on treatment for a year (Vollmer et al. AAN 2020; abstract S29.002). A study followed 546 patients with MS and NMOSD treated with ocrelizumab or rituximab for a mean of 30 months. Overall, 10.5% had lymphopenia, 37.9% had low IgM and 7.4% had low IgG. The time course was lymphopenia (mean 11.3 months after initiation), low IgM (19.7 months) and low IgG (36.1 months). Among those with low IgG, 73.9% had prior low IgM.