Activity

Activity ID

12837

Expires

October 2, 2026

Format Type

Journal-based

CME Credit

1

Fee

$30

CME Provider: JAMA Neurology

Description of CME Course

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 sclerosisPIRAprogression independent of relapse activitysilent 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.

Disclaimers

1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.

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NOTE: If a Member Board has not deemed this activity for MOC approval as an accredited CME activity, this activity may count toward an ABMS Member Board’s general CME requirement. Please refer directly to your Member Board’s MOC Part II Lifelong Learning and Self-Assessment Program Requirements.

Educational Objectives

To identify the key insights or developments described in this article

Keywords

Demyelinating Disorders, Multiple Sclerosis, Neurology

Competencies

Medical Knowledge

CME Credit Type

AMA PRA Category 1 Credit

DOI

10.1001/jamaneurol.2023.3331

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