Monash University
Central Clinical School

Author Of 1 Presentation

Observational Studies Poster Presentation

P0859 - Comparative effectiveness of natalizumab, fingolimod, and first-line therapies for rapidly evolving severe relapsing-remitting multiple sclerosis (ID 1551)

Abstract

Background

Natalizumab and fingolimod are indicated in the EU for patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES RRMS; ≥2 relapses in 1 year and ≥1 gadolinium-enhancing lesions or increased T2 lesion numbers on MRI) or highly active RRMS. Patients with RRMS may also receive first-line therapies (interferon beta, glatiramer acetate, dimethyl fumarate, or teriflunomide; collectively BRACETD). Effectiveness comparisons of therapies in patients with RES RRMS are lacking.

Objectives

To compare the clinical effectiveness of natalizumab, fingolimod, and BRACETD in patients with RES RRMS in real-world settings.

Methods

Data from the MSBase registry as of August 2019 were used. Adults with RRMS, ≥2 relapses in the past 12 months, and available Expanded Disability Status Scale scores at baseline (BL) and on therapy were included. At index date, patients were treatment naive or had switched from BRACETD to natalizumab, fingolimod, or another BRACETD. Patients were propensity score matched 1:1:1 based on BL demographic and clinical variables. Annualized relapse rates (ARRs) were compared using a generalised estimating equation Poisson regression model. Other outcomes (time to first relapse, 6-month confirmed disability worsening [CDW], and 6-month confirmed disability improvement [CDI]) were analysed using Cox marginal regression models.

Results

Matched treatment groups included 721 triplets of patients with mean follow-up of approximately 3 years. In each group, 23.3–23.9% of patients were treatment naïve. ARR (95% CI) was lowest with natalizumab (0.18 [0.17–0.20]) followed by fingolimod (0.29 [0.26–0.31]) and BRACETD (0.39 [0.37–0.42]; P<0.001 for all comparisons); rate ratio (95% CI) vs BRACETD was 0.46 (0.42–0.53) for natalizumab and 0.72 (0.65–0.80) for fingolimod. Risk of first relapse was lower with natalizumab vs fingolimod (hazard ratio [HR] [95% CI], 0.63 [0.53–0.74]) or BRACETD (0.41 [0.36–0.48]; P<0.001 for both) and with fingolimod vs BRACETD (0.66 [0.57–0.76]; P<0.001). No differences in CDW were observed. CDI was more likely with natalizumab than with fingolimod (HR [95% CI], 1.25 [1.01–1.55]; P=0.047) or BRACETD (1.46 [1.16–1.85]; P=0.002). CDI was not significantly different between fingolimod and BRACETD (HR [95% CI], 1.17 [0.91–1.50]; P=0.209).

Conclusions

In this large cohort of patients with RES RRMS treated in real-world settings, natalizumab was more effective than fingolimod or BRACETD at reducing relapses. Natalizumab patients were also 25% and 46% more likely to exhibit CDI than fingolimod and BRACETD patients, respectively.

This study was supported by Biogen International (Zug, Switzerland).

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Presenter Of 1 Presentation

Observational Studies Poster Presentation

P0859 - Comparative effectiveness of natalizumab, fingolimod, and first-line therapies for rapidly evolving severe relapsing-remitting multiple sclerosis (ID 1551)

Abstract

Background

Natalizumab and fingolimod are indicated in the EU for patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES RRMS; ≥2 relapses in 1 year and ≥1 gadolinium-enhancing lesions or increased T2 lesion numbers on MRI) or highly active RRMS. Patients with RRMS may also receive first-line therapies (interferon beta, glatiramer acetate, dimethyl fumarate, or teriflunomide; collectively BRACETD). Effectiveness comparisons of therapies in patients with RES RRMS are lacking.

Objectives

To compare the clinical effectiveness of natalizumab, fingolimod, and BRACETD in patients with RES RRMS in real-world settings.

Methods

Data from the MSBase registry as of August 2019 were used. Adults with RRMS, ≥2 relapses in the past 12 months, and available Expanded Disability Status Scale scores at baseline (BL) and on therapy were included. At index date, patients were treatment naive or had switched from BRACETD to natalizumab, fingolimod, or another BRACETD. Patients were propensity score matched 1:1:1 based on BL demographic and clinical variables. Annualized relapse rates (ARRs) were compared using a generalised estimating equation Poisson regression model. Other outcomes (time to first relapse, 6-month confirmed disability worsening [CDW], and 6-month confirmed disability improvement [CDI]) were analysed using Cox marginal regression models.

Results

Matched treatment groups included 721 triplets of patients with mean follow-up of approximately 3 years. In each group, 23.3–23.9% of patients were treatment naïve. ARR (95% CI) was lowest with natalizumab (0.18 [0.17–0.20]) followed by fingolimod (0.29 [0.26–0.31]) and BRACETD (0.39 [0.37–0.42]; P<0.001 for all comparisons); rate ratio (95% CI) vs BRACETD was 0.46 (0.42–0.53) for natalizumab and 0.72 (0.65–0.80) for fingolimod. Risk of first relapse was lower with natalizumab vs fingolimod (hazard ratio [HR] [95% CI], 0.63 [0.53–0.74]) or BRACETD (0.41 [0.36–0.48]; P<0.001 for both) and with fingolimod vs BRACETD (0.66 [0.57–0.76]; P<0.001). No differences in CDW were observed. CDI was more likely with natalizumab than with fingolimod (HR [95% CI], 1.25 [1.01–1.55]; P=0.047) or BRACETD (1.46 [1.16–1.85]; P=0.002). CDI was not significantly different between fingolimod and BRACETD (HR [95% CI], 1.17 [0.91–1.50]; P=0.209).

Conclusions

In this large cohort of patients with RES RRMS treated in real-world settings, natalizumab was more effective than fingolimod or BRACETD at reducing relapses. Natalizumab patients were also 25% and 46% more likely to exhibit CDI than fingolimod and BRACETD patients, respectively.

This study was supported by Biogen International (Zug, Switzerland).

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