Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis.


Journal

Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247

Informations de publication

Date de publication:
Jul 2021
Historique:
received: 22 12 2020
revised: 15 03 2021
accepted: 16 04 2021
pubmed: 13 5 2021
medline: 7 7 2021
entrez: 12 5 2021
Statut: ppublish

Résumé

A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS. A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI. In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

Sections du résumé

BACKGROUND BACKGROUND
A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS.
METHODS METHODS
A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.
RESULTS RESULTS
After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI.
CONCLUSION CONCLUSIONS
In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

Identifiants

pubmed: 33979770
pii: S2211-0348(21)00239-X
doi: 10.1016/j.msard.2021.102972
pii:
doi:

Substances chimiques

Crotonates 0
Hydroxybutyrates 0
Immunosuppressive Agents 0
Indans 0
Nitriles 0
Oxadiazoles 0
Toluidines 0
teriflunomide 1C058IKG3B
ozanimod Z80293URPV

Types de publication

Journal Article Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

102972

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Stanley Cohan (S)

Providence Multiple Sclerosis Center, Providence Brain and Spine Institute, 2805 NE Glisan St., Portland, OR, 97213 USA. Electronic address: Stanley.Cohan@providence.org.

Tom Tencer (T)

Bristol Myers Squibb, 3551 Lawrenceville Rd., Princeton, NJ, 08540 USA.

Stella Arndorfer (S)

Genesis Research, 5 Marine View Plaza, Hoboken, NJ, 07030 USA.

Xuelian Zhu (X)

Genesis Research, 5 Marine View Plaza, Hoboken, NJ, 07030 USA.

Marko Zivkovic (M)

Genesis Research, 5 Marine View Plaza, Hoboken, NJ, 07030 USA.

Jinender Kumar (J)

Bristol Myers Squibb, 3551 Lawrenceville Rd., Princeton, NJ, 08540 USA.

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Classifications MeSH