Abstract
Objective Progression independent of relapse activity (PIRA) is a disruptive concept in multiple sclerosis (MS) research and practice. To address the significant heterogeneity of studies in this field, we conducted a systematic review to propose a clinically applicable criteria-based definition of PIRA to assist ongoing investigations.
Method This systematic review was conducted and reported in accordance with the PRISMA guidelines. A systematic search was conducted of Embase, Medline, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, ClinicalTrials.gov and Google Scholar.
Results Of 5,812 results, 13 studies fulfilled inclusion criteria. Most studies included only relapsing remitting MS (RRMS), although a number also included patients with secondary progressive MS. PIRA definitions varied considerably between studies. Studies used a tiered system, including up to three tiers, for Expanded Disability Status Scale thresholds that described PIRA. The duration of time prior to relapse that PIRA must have occurred ranged from > 30 days to > 12 months. In the context of these variable definitions, the reported proportion of patients experiencing PIRA varied from 4% to 24%. Similarly, PIRA associations varied; however, low EDSS was among the most consistently described associations. Most studies did not include MRI in the determination of PIRA, which is a significant limitation of existing criteria.
Conclusions The currently available research supports the presence of PIRA in RRMS. Existing studies have used variable definitions of PIRA. Based on review of the existing literature, a clinically based definition of PIRA is proposed to harmonize this phenomenon for future studies.
