ArticleMultiple sclerosis (Houndmills, Basingstoke, England)2023
The impact of relapse definition and measures of durability on MS clinical trial outcomes.
Article in Multiple sclerosis (Houndmills, Basingstoke, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Retinal Layer Thickness for Risk Stratification of Progression Independent of Relapse Activity in Relapsing-Remitting Multiple Sclerosis.Brain and behavior · 2026Observational
- Secondary progression activity monitoring in MS despite an early highly active treatment the SPAM study.European journal of neurology · 2025Article
- Progression independent of relapsing biology in multiple sclerosis: a real-word study.Frontiers in neurology · 2025Article
- Relapse-Associated and Relapse-Independent Contribution to Overall Expanded Disability Status Scale Progression in Multiple Sclerosis Patients Diagnosed in Different Eras.Annals of neurology · 2024Article
- The global patient-reported outcomes for multiple sclerosis initiative: bridging the gap between clinical research and care - updates at the 2023 plenary event.Frontiers in neurology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDefinitions of trial measures are consequential to accurately capturing outcomes and cross-trial comparability, particularly for derivative measures.
objectiveUsing CombiRx, examine the impact of relapse definition on endpoints and evaluate the durability of progression measures in Relapsing Remitting Multiple Sclerosis (RRMS).
methodsCombiRx relapse types were distinguished by the presence or timing of Expanded Disability Status Scale (EDSS) increase. Using the broadest definition of relapse, progression endpoints were assessed in patients without relapses on trial. Durability compared EDSS at study end and time of worsening.
resultsBroadening relapse definition to the most inclusive definition increased annualized relapse rate (ARR) threefold in all arms and decreased progression independent of relapse activity (PIRA), defined as 6-month confirmed disability worsening (6M CDW) without relapse, by 44%. Neither PIRA nor PIA (progression independent of any inflammatory activity) guaranteed durable worsening, with 43% and 40%, respectively, improving by end of study. Multivariate analysis showed two CDW events, not relapse, predicted durability among patients meeting 6M CDW.
conclusionsThe stringency of relapse definition impacted absolute ARR and composite endpoints in RRMS. Despite the most generous relapse definition, 43% of patients meeting PIRA on trial did not have durable worsening suggesting that relapse definition and durability should be considered to avoid overestimating progression in RRMS trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.