AAN 2020 DAILY REPORT – TUESDAY, APRIL 28 EDITION

 

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.

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CONGRESS HIGHLIGHTS – TUESDAY EDITION

Migraine
Oral and injectable anti-CGRP agents

Insomnia
Lemborexant in insomnia

Multiple sclerosis
MSBase – Long-term disability outcomes with DMTs
Ocrelizumab – long-term effect on disability
How many have SPMS?
Siponimod and meningeal follicles

NMOSD
Safety data for satralizumab

Clinical tip of the day

Migraine

Oral and injectable anti-CGRP agents: Rimegepant, an oral agent targeting calcitonin gene-related peptide (CGRP), was recently approved by the FDA for acute migraine. A matching-adjusted indirect comparison reported that efficacy (monthly migraine days, MMD) was similar to that seen with the injectable anti-CGRP drugs galcanezumab and erenumab approved for migraine prophylaxis (Popoff et al. AAN 2020; abstract P1.010). A separate study (n=13) found that rimegepant 75 mg was well-tolerated if administered for acute migraines in patients who were already taking an injectable anti-CGRP MAb for migraine prophylaxis (Berman et al. AAN 2020; abstract S8.008). No serious adverse events, including elevated liver enzymes >3x ULN, were reported. Coadministration of rimegepant and subcutaneous sumatriptan does not appear to have a clinically significant effect on blood pressure (Hanna et al. AAN 2020; abstract P3.010).

Insomnia

Lemborexant in insomnia: Lemborexant is a dual orexin receptor blocker approved by the FDA in December 2019 for the treatment of insomnia. In the unpublished phase III SUNRISE-2 trial, 949 patients were randomized to lemborexant 5 or 10 mg/day or placebo for 6 months; the placebo group was re-randomized to active treatment for another 6 months (Moline et al. AAN 2010; P2.011). There were significant decreases in Insomnia Severity Index scores in both active treatment arms vs. placebo (-9.5 and -9.7 vs. -7.4) as well as in Fatigue Severity Scores (-8.9 and -9.0 vs. -6.4) at 6 months with further improvement at 12 months. SUNRISE I, a one-month comparison of lemborexant vs. zolpidem and placebo, was published last year (Rosenberg et al. JAMA Netw Open 2019;2:e1918254.

Multiple sclerosis

MSBase – Long-term disability outcomes with DMTs: An analysis by the MSBase group (n=24,884) estimated that disease-modifying therapies (DMTs) reduce long-term disability accrual by about 26% compared to no treatment (Kalincik et al. AAN 2020; abstract P5.008). However, this treatment effect declined with level of disability (-8%/EDSS step), recent disability worsening while on treatment (-14%) and recent on-treatment relapses (-43% per relapse). Disability improvements declined with age (-2%/year), disease duration (-6%/year) and disability (-8%/EDSS step).

Ocrelizumab – long-term effect on disability: Patients receiving continuous ocrelizumab in the OPERA trials and open-label extension had a lower risk of disability progression compared to the interferon/ocrelizumab switch group (Giovannoni et al. AAN 2020; abstract P3.010). Over the 6-year period, the proportion of patients on continuous ocrelizumab with 24-week confirmed disability progression was 10.1% after 3 years, 13.9% at 4 years, 16.2% at 5 years and 19.2% at 6 years.

How many have SPMS? A comparison of three MS registries in the UK, Germany and Sweden found significant differences in the prevalence of SPMS (Forsberg et al. AAN 2020; abstract P4.011). The proportion of SPMS patients in the national databases was 13.8% in the UK, 16.6% in Germany and 24.5% in Sweden. The prevalence of SPMS was as high as 25-36% when a novel decision tree tool (Ramanujam et al. ECTRIMS 2016; abstract P897) that inputs clinical and demographic data was used.

Siponimod and meningeal follicles: A novel study has demonstrated that the sphingosine-1 receptor modulator siponimod can reduce the extent of ectopic lymphoid tissue formation in the spinal cord in an EAE model (Lehmann-Horn et al/ AAN 2020; abstract p3.005). A reduction in meningeal lymphoid tissue was associated with a less severe clinical course. Previous animal studies have demonstrated a reduction in astrogliosis and microgliosis with siponimod independent of the drug’s effects on peripheral immune cells (Gentile et al. J Neuroinflammation 2016;13:207).

NMOSD

Safety data for satralizumab: Satralizumab is an anti-IL6 MAb in development for neuromyelitis optica spectrum disorder. Phase III results were presented last year (see ECTRIMS 2019 slide deck. NeuroSens, September 26, 2019). A pooled analysis of two phase III studies (N=178) found lower rates of infections and serious adverse events with satralizumab compared to placebo (Greenberg et al. AAN 2020; abstract S34.003). The most common adverse events were UTI and upper respiratory tract infection.

Clinical tip of the day: Optic neuritis may be more severe in males who are obese (Chu et al. AAN 2020; abstract 4.012). Optic neuritis severity was examined in CIS patients enrolled in the CLIMB trial (n=61). BMI was significantly higher among males with moderate/severe versus mild ON (31.26 vs. 25.73 kg/m2); obesity was associated with significantly higher estradiol levels (34.24 nmol/L vs. 23.06 nmol/L), with a trend to higher serum leptin (12.29 ng/mL vs. 4.1 ng/mL). Similar associations were not found for female CIS patients.

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