Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study

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).

Conflict of interest statement

Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su and Roger Chang were employees of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen. Robin L. Avila and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Laura Balcer is editor-in-chief of the Journal of Neuro-Ophthalmology. Steven Galetta has received consulting fees from Biogen and Genentech. Robert J. Fox has received personal consulting fees from AB Science, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, Janssen, Novartis, Sanofi, and TG Therapeutics; has served on advisory committees for AB Science, Biogen, Genzyme, Immunic, Janssen, Novartis, Sanofi, and TG Therapeutics; and has received clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi.

© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Figures

Fig. 1

Cumulative probability for time to confirmed disability improvement (CDI) over 4 years in the intent-to-treat population. Time point shown is for onset of Expanded Disability Status Scale score decrease, which was confirmed 24 weeks later. Dashed lines show the 95% confidence interval

Fig. 2

Proportion of patients experiencing worsening, stability, or improvement in Multiple Sclerosis Impact Scale (MSIS-29) scores at year 4 compared with baseline in the intent-to-treat (ITT) and 4-year completer populations

Fig. 3

Proportion of patients with clinically meaningful improvements on their SDMT (Symbol Digit Modalities Test) score (≥ 4) who exhibited worsening, stability, or improvement on patient-reported outcomes at year 4. MSIS-29 is categorical change in physical and psychological scores. For WPAI, hours of work missed/week and impact on regular activities are due to multiple sclerosis (MS) (impact on regular activities assessed in all patients regardless of employment status). MSIS-29 Multiple Sclerosis Impact Scale, WPAI Work Productivity and Activity Impairment Questionnaire

Fig. 4

Proportion of patients with clinically meaningful improvements on their SDMT score (≥ 4) who achieved NEDA, Clinical NEDA, or MRI NEDA at year 4. NEDA was defined as no relapses or 24-week CDW, no Gd+ lesions, and no new or newly enlarging T2 lesions (CDW was defined as a ≥ 1.5-point increase from a baseline EDSS score of 0.0, a ≥ 1.0-point increase from a baseline EDSS score of 1.0 to CDW confirmed disability worsening; EDSS Expanded Disability Status Scale; Gd+ gadolinium-enhancing; MRI magnetic resonance imaging; NEDA No Evidence of Disease Activity

Fig. 5

Proportion of ITT patients with confirmed disability improvement who exhibited worsening, stability, or improvement on patient-reported outcomes at year 4. MSIS-29 is categorical change in physical and psychological scores. For WPAI, hours of work missed/week and impact on regular activities are due to MS (impact on regular activities assessed in all patients regardless of employment status). ITT Intent-to-treat; MSIS-29 Multiple Sclerosis Impact Scale; WPAI Work Productivity and Activity Impairment Questionnaire

Fig. 6

Proportions of ITT patients with confirmed disability improvement who achieved NEDA, Clinical NEDA, or MRI NEDA at year 4. NEDA was defined as no relapses or 24-week CDW, no Gd+ lesions, and no new or newly enlarging T2 lesions (CDW was defined as a ≥ 1.5-point increase from a baseline EDSS score of 0.0, a ≥ 1.0-point increase from a baseline EDSS score of 1.0 to CDW confirmed disability worsening; EDSS Expanded Disability Status Scale; Gd+ gadolinium-enhancing; ITT Intent-to-treat; MRI magnetic resonance imaging; NEDA No Evidence of Disease Activity