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- Title
(DXT24) Two Expanded Disability Status Scale Subscales Evaluated in Patients with Relapsing-Remitting or Secondary Progressive Multiple Sclerosis.
- Authors
Cutter, Gary; Xiangyi Meng; Weiss, Jamie L.; Benedict, Ralph H. B.; Cohan, Stanley L.; Cree, Bruce A. C.; Su, Wendy; Thomas, Florian P.
- Abstract
Background: In phase 3 trials using the Expanded Disability Status Scale (EDSS), fingolimod and siponimod reduced disability worsening in patients with relapsing-remitting (RRMS) and secondary progressive multiple sclerosis (SPMS), respectively. However, EDSS components may differentially contribute to worsening, and contribution of each component may depend on disease stage. Also, EDSS assessments can be burdensome for patients and clinicians. Using factor analysis, different EDSS functions can be allocated to 2 novel subscales, including parameters most relevant to disease worsening. Objectives: Evaluate the effects of fingolimod and siponimod using EDSS subscales derived by factor analysis of phase 3 trial data. Methods: PROC FACTOR procedure was used to determine best fit of baseline EDSS data to the following subscales: Motor Integration (MI: ambulation, cerebellar, and pyramidal functions) and Collateral (C: bowel and bladder, brainstem, cerebral, sensory, and visual functions). Treatment effect sizes (ESs) on disability (mean change from baseline vs placebo) were determined overall and by each subscale up to 24 months (M) in patients with RRMS from FREEDOMS and up to 27M in patients with SPMS from EXPAND. Statistical significance was assessed using rank analysis of covariance (FREEDOMS) and a covariance mixed-effect, repeat-measurement model (EXPAND). Subgroup analyses of patients in EXPAND with/without lesion activity or relapses prior to screening were also performed and will be presented. Analyses were for hypothesis generation without multiple comparison adjustment. Results: Treatment ESs in FREEDOMS (N = 843: fingolimod, n = 425; placebo, n = 418) at 24 months were -0.14, P = .002 (EDSS); -0.18, P = .002 (MI); and -0.07, P = .081 (C). Significant effects (P < .05) were seen on MI from M6; effects on C were mostly nonsignificant. In EXPAND (N = 1645: siponimod, n = 1099; placebo, n = 546), overall treatment effects were detected over 27M for EDSS (P = .020), MI (P = .014), and C (P = .021). Significant ESs were seen on MI (all P < .01) at M9 (-0.28), M15 (-0.34), and M18 (-0.34), and on C at M18 (-0.24, P < .05) and M27 (-0.54, P < .001). Conclusions: The benefits of fingolimod in patients with RRMS mainly affected the MI subscale. For patients with SPMS, the benefits of siponimod were seen on both MI and C. In SPMS, effects on MI appeared earlier than on C, however the largest ES was seen later on C. Defining EDSS subscales with factor analyses may help improve their clinical usefulness.
- Subjects
CLINICAL trials; CONFERENCES &; conventions; IMMUNOSUPPRESSIVE agents; MULTIPLE sclerosis; DISEASE relapse; TREATMENT effectiveness; SPHINGOSINE-1-phosphate
- Publication
International Journal of MS Care, 2020, Vol 22, Issue S2, p24
- ISSN
1537-2073
- Publication type
Article