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Comparative efficacy of switching to natalizumab in active multiple sclerosis.

ABSTRACT: OBJECTIVE: To compare treatment efficacy and persistence in patients who switched to natalizumab versus those who switched between glatiramer acetate (GA) and interferon-beta (IFN?) after an on-treatment relapse on IFN? or GA using propensity score matched real-world datasets. METHODS: Patients included were registered in MSBase or the TYSABRI Observational Program (TOP), had relapsed on IFN? or GA within 12 months prior to switching to another therapy, and had initiated natalizumab or IFN?/GA treatment ?6 months after discontinuing prior therapy. Covariates were balanced across post switch treatment groups by propensity score matching at treatment initiation. Relapse, persistence, and disability measures were compared between matched treatment arms in the total population (n = 869/group) and in subgroups defined by prior treatment history (IFN? only [n = 578/group], GA only [n = 165/group], or both IFN? and GA [n = 176/group]). RESULTS: Compared to switching between IFN? and GA, switching to natalizumab reduced annualized relapse rate in year one by 65-75%, the risk of first relapse by 53-82% (mean follow-up 1.7-2.2 years) and treatment discontinuation events by 48-65% (all P ? 0.001). In the total population, switching to natalizumab reduced the risk of confirmed disability progression by 26% (P = 0.036) and decreased the total disability burden by 1.54 EDSS-years (P < 0.0001) over the first 24 months post switch. INTERPRETATION: Using large, real-world, propensity-matched datasets we demonstrate that after a relapse on IFN? or GA, switching to natalizumab (rather than between IFN? and GA) led to superior outcomes for patients in all measures assessed. Results were consistent regardless of the prior treatment identity.

SUBMITTER: Spelman T

PROVIDER: S-EPMC4402083 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman Timothy T Kalincik Tomas T Zhang Annie A Pellegrini Fabio F Wiendl Heinz H Kappos Ludwig L Tsvetkova Larisa L Belachew Shibeshih S Hyde Robert R Verheul Freek F Grand-Maison Francois F Izquierdo Guillermo G Grammond Pierre P Duquette Pierre P Lugaresi Alessandra A Lechner-Scott Jeannette J Oreja-Guevara Celia C Hupperts Raymond R Petersen Thor T Barnett Michael M Trojano Maria M Butzkueven Helmut H

Annals of clinical and translational neurology 20150227 4

<h4>Objective</h4>To compare treatment efficacy and persistence in patients who switched to natalizumab versus those who switched between glatiramer acetate (GA) and interferon-beta (IFNβ) after an on-treatment relapse on IFNβ or GA using propensity score matched real-world datasets.<h4>Methods</h4>Patients included were registered in MSBase or the TYSABRI Observational Program (TOP), had relapsed on IFNβ or GA within 12 months prior to switching to another therapy, and had initiated natalizumab ...[more]

PMID: 25909083

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Project description:Background: Natalizumab (NTZ) and fingolimod (FTY) are second-line disease modifying treatments (DMTs) approved for Relapsing - Remitting Multiple Sclerosis (RRMS). Few studies are available on a direct comparison between NTZ and FTY, based on post-marketing experience, with conflicting results and reporting relatively short follow-up period. Aim: We hereby report real-world experience of a MS Center with respect to NTZ vs. FTY comparison in terms of efficacy and safety, referencing long-term follow-up. Methods: We used retrospective data for all patients that received 2nd-line treatment NTZ (since May 2007) or FTY (since September 2011). Primary endpoints were, among others, annual EDSS score (mean change from baseline), time to disability worsening or improvement, Annualized Relapse Rate (ARR) after 12 and 24 months and upon total treatment duration, time to first relapse and time to radiological progression. Results: A total of 138 unmatched patients, 84 treated with NTZ and 54 treated with FTY were included. Following Propensity Score (PS) matching, 31 patients in each group were retained. Mean follow-up period for NTZ- and FTY-treated patients was 4.43 ± 0.29 and 3.59 ± 0.32 years (p = 0.057), respectively. In the matched analysis, time to disability improvement and time to disability worsening was comparable between groups. A higher proportion of patients remained free of relapse under NTZ, compared to FTY (Log Rank test p = 0.021, HR: 0.25, 95% CI: 0.08-0.8), as well as free of MRI activity (Log Rank test p = 0.006, HR: 0.26, 95% CI: 0.08-0.6). Treatment discontinuation due to MRI activity was significantly higher for FTY-treated patients compared to NTZ (Log Rank test p = 0.019, HR: 0.12, 95% CI: 0.05-0.76). Conclusion: Our results indicate toward NTZ superiority with respect to relapse and MRI activity outcomes. The fact that NTZ-treated patients may achieve long-standing clinical and radiological remission points toward the need for long follow-up data.

Project description:The objective of this study was to investigate confirmed progression independent of relapse activity in relapsing-remitting multiple sclerosis patients under long-term natalizumab treatment. We performed a retrospective, cross-sectional study of clinical data captured between 1994 and 2019 at two German multiple sclerosis tertiary referral centres. Data files of all relapsing-remitting multiple sclerosis patients treated with natalizumab for ≥24 months were analysed. Confirmed progression independent of relapse activity was defined as ≥12 week confirmed disability progression on a roving Expanded Disability Status Scale reference score by 1 point in patients with an Expanded Disability Status Scale score ≤3 or 0.5 in patients with an Expanded Disability Status Scale score ≥3.5 in the absence of a relapse. Cox proportional hazard models were used to analyse the probability of developing confirmed progression independent of relapse activity depending on both disease and natalizumab treatment duration. Among the 184 patients identified, 44 (24%) developed confirmed progression independent of relapse activity under natalizumab irrespective of the Expanded Disability Status Scale score at natalizumab onset. Time to confirmed progression independent of relapse activity was not affected by Expanded Disability Status Scale at natalizumab onset (categorized by Expanded Disability Status Scale score ≤3.5 versus >3.5) nor by duration of disease nor by duration of therapy. Confirmed progression independent of relapse activity occurred earlier in the disease course in patients with an earlier natalizumab therapy onset with regard to disease duration. A stepwise forward regression analysis revealed disease duration as the main factor for confirmed progression independent of relapse activity development (P = 0.005). Taken together, confirmed progression independent of relapse activity occurs in a substantial proportion of patients on long-term natalizumab treatment and independent of Expanded Disability Status Scale score at natalizumab onset. Our findings suggest that patients who are initiated on natalizumab early during disease course, usually in order to treat an aggressive clinical phenotype, have a higher risk of early confirmed progression independent of relapse activity.

Dataset Information

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Publications

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

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