Jai Perumal1, Roumen Balabanov2, Ray Su3, Roger Chang3, Laura J Balcer4, Steven L Galetta4, Robin L Avila3, Danette Rutledge3, Robert J Fox5. 1. Weill Cornell Medical College, Cornell University, 1305 York Ave #2F, New York, NY, 10065, USA. jaisperumal@gmail.com. 2. Northwestern University, Chicago, IL, USA. 3. Biogen, Cambridge, MA, USA. 4. New York University Grossman School of Medicine, New York, NY, USA. 5. Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA.
Abstract
BACKGROUND: STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs). METHODS: Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study. CONCLUSION: These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients. CLINICALTRIALS: GOV: NCT01485003 (5 December 2011).
BACKGROUND: STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs). METHODS: Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study. CONCLUSION: These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients. CLINICALTRIALS: GOV: NCT01485003 (5 December 2011).
Authors: Carrie M Hersh; Bernd Kieseier; Carl de Moor; Deborah M Miller; Denise Campagnolo; James R Williams; Kathryn C Fitzgerald; Kuangnan Xiong; Marisa P McGinley; Megan Hyland; Richard A Rudick; Tjalf Ziemssen; Irene Koulinska Journal: Mult Scler J Exp Transl Clin Date: 2021-04-15