Real-world improvement across functional systems (FS) in relapsing-remitting multiple sclerosis (RRMS) patients treated with natalizumab in the TYSABRI® Observational Program (TOP) (P6.383)

Objective: To identify changes in neurological functioning assessed by confirmed FS improvement (CFSI) in TOP, an ongoing observational study of RRMS patients initiating natalizumab in real-world settings. Background: Natalizumab is a high-efficacy RRMS therapy associated with disability improvement based on Expanded Disability Status Scale (EDSS) score decrease. Assessing disability using EDSS alone may limit detection of improvement in domains unrelated to ambulation. FS complement EDSS and use seven independent scales to evaluate neurological function. Design/Methods: Patients enrolled in TOP as of November 2016 were included. In patients with FS impairment (baseline score ≥1.0 in any FS), CFSI (≥1.0-point decrease in the impaired FS lasting ≥24 weeks) was evaluated. Kaplan-Meier analyses estimated likelihoods of achieving and maintaining CFSI. Results: At baseline, most patients (5073/5993; 84.6%) had impairment in ≥1 FS. Impairment was most common in the pyramidal (88.5%), sensory (75.6%), and cerebellar (66.1%) systems, with no apparent pattern of coincident impairment across FS. Most patients (60.5%) experienced CFSI in ≥1 FS; the cumulative probability of CFSI in any FS during follow-up (median [range]: 2.92 [0–9.5] years) was 96%. For individual FS, the cumulative probability of improvement ranged from 42%–64% (least likely for the pyramidal and most likely for the visual system). Compared with treatment-naive patients, CFSI in any FS was less likely for patients with 1 (hazard ratio [HR]: 0.83; P =0.0033) or ≥2 prior therapies (HR: 0.73; P 50% over 3 years, and mean duration of CFSI was 2.2–2.4 years. Conclusions: Natalizumab-associated improvements were observed across all FS; most patients had CFSI in ≥1 FS. Natalizumab’s potential to improve patients’ functioning across FS domains may provide meaningful context for considering disability improvement in its efficacy profile. Study Supported by: Biogen Disclosure: Dr. Wiendl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche Ltd, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA. Dr. Wiendl has received research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme. Dr. Butzkueven has nothing to disclose. Dr. Kappos has received research support from Bayer HealthCare Pharmaceuticals, Biogen, F. Hoffmann-La Roche Ltd and Genentech,Novartis, Research grants from: the European Union, Roche Research Foundation, Swiss Multiple Sclerosis Society and Swiss National Research Foundation. Dr. Spelman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis. Dr. Trojano has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck Serono, Novartis, Sanofi, Teva. Dr. Trojano has received research support from Biogen, Merck Serono, Novartis. Dr. Rosales has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Campbell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Ho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Licata has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen.