Effect of Siponimod on Disability in EXPAND Re-examined with Two New Subscales of the Expanded Disability Status Scale in Patients with SPMS
Gary Cutter1, Xiangyi Meng2, Amit Bar-Or3, Ralph HB Benedict4, Stanley L Cohan5, Nina Jaitly2, Wendy Su2, Davorka Tomic6, Bruce AC Cree7
1UAB School of Public Health, Birmingham, AL, USA, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 3Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, 4University at Buffalo, State University of New York, Buffalo, NY, USA, 5Providence Multiple Sclerosis Center, Providence Brain and Spine Institute, Portland, OR, USA, 6Novartis Pharma AG, Basel, Switzerland, 7UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
Objective:
Evaluate treatment effects of siponimod on two different Expanded Disability Status Scale (EDSS) subscales in the EXPAND trial in patients with secondary progressive multiple sclerosis (SPMS).
Background:
In EXPAND, siponimod 2 mg/day reduced confirmed disability progression (as measured by EDSS) versus placebo over ≤36 months in patients with SPMS.
Design/Methods:
Two subscales were developed: Motor Integration (MI: ambulation, cerebellar/pyramidal functions) and Collateral (C: bowel and bladder, brainstem, cerebral, sensory and visual functions). Treatment differences (change from baseline in each subscale) were assessed using analysis of covariance mixed-effect model repeat-measurement model, with treatment, time point (and their interaction), country/region and baseline relapse status as factors, and corresponding baseline as covariates. Analyses were for all patients, patients with/without relapses during 24 months before enrollment and patients with/without gadolinium-enhancing lesions at baseline. Effect sizes (ES) were calculated for each time point. Analyses for hypothesis generation; no adjustment for multiple comparisons.
Results:
Data were analyzed for 1645 patients (siponimod, n=1099; placebo, n=546). Treatment effects were detected over 36 months for EDSS (p=0.020) and both subscales (MI: p=0.014; C: p=0.021); ES favoring siponimod were observed from 6 months onwards. MI subscale detected marked ES at Month 9 in all patients (0.12; p=0.007), the relapsing subgroup (0.25; p=0.009) and patients without lesions (0.13; p=0.012); and at Month 12 in those with lesions (0.22; p=0.041). Treatment effects were detected later with C subscale than with MI. The C subscale detected marked ES at Month 15 for the relapsing subgroup (0.19; p<0.05) and Month 27 for patients with (0.43; p<0.05) and without lesions (0.29; p<0.05).
Conclusions:
Treatment effects were detected earlier in MI than C subscales. These findings are consistent with earlier EDSS subscale analyses of fingolimod data, and confirm the efficacy of siponimod on disability progression in patients with SPMS.