Course: Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis: A Systematic Review
CME Credits: 1.00
Released: 2023-10-02
Key Points
Question What is the current evidence on progression independent of relapse activity (PIRA) in multiple sclerosis (MS), and what definition and terminology is used in the literature?Findings In this systematic review of 48 studies, PIRA was found to be the most common form of disability accumulation across all traditional MS phenotypes, including clinically isolated syndrome and early relapsing-remitting MS. However, there is no uniform definition of PIRA in the literature.
Meaning Acknowledging the occurrence of PIRA may lead to a better understanding of the drivers of MS evolution and more targeted interventions in clinical trials and practice; a harmonized definition could improve comparability of results in current and future studies.
Abstract
Importance Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.Objective To summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials.
Evidence Review A literature search was conducted using the search terms multiple sclerosis, PIRA, progression independent of relapse activity, silent progression, and progression unrelated to relapses in PubMed, Embase, Cochrane, and Web of Science, published between January 1990 and December 2022.
Findings Of 119 identified single records, 48 eligible studies were analyzed. PIRA was reported to occur in roughly 5% of all patients with RRMS per annum, causing at least 50% of all disability accrual events in typical RRMS. The proportion of PIRA vs relapse-associated worsening increased with age, longer disease duration, and, despite lower absolute event numbers, potent suppression of relapses by highly effective disease-modifying therapy. However, different studies used various definitions of PIRA, rendering the comparability of studies difficult.
Conclusion and Relevance PIRA is the most frequent manifestation of disability accumulation across the full spectrum of traditional MS phenotypes, including clinically isolated syndrome and early RRMS. The harmonized definition suggested here may improve the comparability of results in current and future cohorts and data sets.
To identify the key insights or developments described in this article
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