Natalizumab improves ambulation in relapsing−remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM

Abstract

Background and purposeImpaired ambulation is a prominent disabling symptom of multiple sclerosis and can lead to reduced quality of life. Whether natalizumab, a monoclonal antibody shown to reduce disease activity in relapsing−remitting multiple sclerosis, could impact ambulation performance was examined.MethodsA prospective open-label study, TIMER, was conducted in natalizumab-naive patients (n = 215). The timed 25-foot walk (T25FW) and timed 100-m walk (T100MW) were assessed at baseline and at weeks 24 and 48 of natalizumab therapy, together with Expanded Disability Status Scale scores. The effects of natalizumab on T25FW performance were also examined in a retrospective analysis of natalizumab-treated patients (n = 627) and placebo control patients (n = 315) from the AFFIRM study.ResultsIn TIMER, a significant increase from baseline in T25FW speed was seen at week 24 (P = 0.0074) and in T100MW speed at weeks 24 and 48 (both P < 0.001). A greater proportion of patients showed clinically meaningful increases (≥20%) in walking speed on the T100MW (25%) than on the T25FW (13%) at week 48 (P = 0.032). In AFFIRM, natalizumab increased the proportion of patients with ≥20% confirmed improvement in T25FW speed at year 2 by 78% versus placebo (P = 0.0133).ConclusionsNatalizumab increased walking speed in patients with relapsing−remitting multiple sclerosis. The T100MW may be more sensitive to changes in ambulation capacity than the T25FW, and both tests appear to detect clinically meaningful improvements in ambulatory function.

Predictors of Health Utility in Relapsing–Remitting and Secondary-Progressive Multiple Sclerosis: Implications for Future Economic Models of Disease-Modifying Therapies

“…Based on the findings from two systematic literature reviews of outcome measures in trials in multiple sclerosis, T25FW has been collected in RCTs for all approved DMTs (including the first approved DMTs interferons and glatiramer acetate), [ 21 , 22 ] and will likely continue to be collected in future RCTs of MS, owing in part to the growing interest in evaluating the efficacy of DMTs using multiple disability measures in clinical trials of MS [ 75 ]. T25FW has been reported for various DMTs, for example, dimethyl fumarate, [ 76 ] fingolimod and interferon beta-1a, [ 77 ] natalizumab, [ 78 ] and peginterferon [ 44 ]. The MSOAC Placebo Database could serve as a source of T25FW, EDSS, and relapse data for other relevant DMTs such as alemtuzumab, glatiramer acetate, and teriflunomide, [ 41 ] if data from the treatment arms of the clinical trials in the database are available to external researchers.…”

A prospective web-based patient-centred interactive study of long-term disabilities, disabilities perception and health-related quality of life in patients with multiple sclerosis in The Netherlands: the Dutch Multiple Sclerosis Study protocol

“…Since about two decades the number and severity of relapses can be reduced by treatment with immunomodulating or immunosuppressive disease modifying drugs (DMDs), as a result of which further increase in disability may be slowed or stopped [ 2 , 3 ]. Long-term treatment with potent DMDs may even lead to an improvement of neurological functions [ 4 ].…”

Revisión sistemática de estudios de calidad de vida y/o productividad laboral en pacientes tratados con natalizumab

“…Finalmente se incluyeron un total de 18 estudios, de los cuales cuatro (22,2%) eran modelizaciones [15][16][17][18], seis estudios evaluaban la calidad de vida en condiciones de práctica clínica habitual tras la administración de natalizumab [19][20][21][22][23][24], tres eran ensayos que evaluaban diferentes medidas de salud reportadas por pacientes (patient reported outcomes [PRO]) [25][26][27] y un estudio evaluaba el efecto de natalizumab sobre la productividad laboral en Suecia [28]. De los restantes dos eran análisis conjuntos [29,30] de los estudios AFFIRM y SENTINEL, estudios clínicos de natalizumab, focalizándose concretamente en evaluar la CVRS, y en tres se aportaban post-hoc análisis del ensayo AFFIRM que relacionaban la capacidad visual [31] y la velocidad de desplazamiento [23,32] con la calidad de vida.…”