AUTHOR=Blok Katelijn M. , van Rosmalen Joost , Tebayna Nura , Smolders Joost , Wokke Beatrijs , de Beukelaar Janet TITLE=Disease activity in primary progressive multiple sclerosis: a systematic review and meta-analysis JOURNAL=Frontiers in Neurology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1277477 DOI=10.3389/fneur.2023.1277477 ISSN=1664-2295 ABSTRACT=Background

Disease activity in multiple sclerosis (MS) is defined as presence of relapses, gadolinium enhancing lesions and/or new or enlarging lesions on MRI. It is associated with efficacy of immunomodulating therapies (IMTs) in primary progressive MS (PPMS). However, a thorough review on disease activity in PPMS is lacking. In relapsing remitting MS, the prevalence of activity decreases in more contemporary cohorts. For PPMS, this is unknown.

Aim

To review disease activity in PPMS cohorts and identify its predictors.

Methods

A systematic search in EMBASE, MEDLINE, Web of science Core Collection, COCHRANE CENTRAL register of trials, and GOOGLE SCHOLAR was performed. Keywords included PPMS, inflammation, and synonyms. We included original studies with predefined available data, extracted cohort characteristics and disease activity outcomes and performed meta-regression analyses.

Results

We included 34 articles describing 7,109 people with PPMS (pwPPMS). The weighted estimated proportion of pwPPMS with overall disease activity was 26.8% (95% CI 20.6–34.0%). A lower age at inclusion predicted higher disease activity (OR 0.91, p = 0.031). Radiological activity (31.9%) was more frequent than relapses (9.2%), and was predicted by longer follow-up duration (OR 1.27, p = 0.033). Year of publication was not correlated with disease activity.

Conclusion

Inflammatory disease activity is common in PPMS and has remained stable over the last decades. Age and follow-up duration predict disease activity, advocating prolonged monitoring of young pwPPMS to evaluate potential IMT benefits.