Pulse Brain · Growing Health Evidence Index
Tier 2 — RCT / large cohortPeer-reviewed

Performance of Composite Endpoints Defining Progression Independent of Relapse Activity in Multiple Sclerosis

Ludwig Kappos, Sean Yiu, Jason Reucassel, Jiwon Oh, Cristina Granziera, Joep Killestein, Robert Bermel, Claude Berge, Agne Kazlauskaite, Hans‐Martin Schneble, Frank Dahlke, Bruce Cree

Annals of Clinical and Translational Neurology · 2025

Read source ↗ All evidence

Summary

This analysis of two large multiple sclerosis trials (OPERA I/II and ENSEMBLE) evaluated the utility of composite progression independent of relapse activity (cPIRA) as a clinical trial endpoint. The study found that cPIRA events were largely independent of MRI activity in ocrelizumab-treated patients and occurred despite low serum neurofilament levels, and that cPIRA independently predicted subsequent disability worsening on multiple measures. The authors conclude cPIRA is a clinically relevant and sensitive endpoint for MS trials.

Regional applicability

This is an international multi-centre trial analysis (primarily European and North American sites) examining methodology for multiple sclerosis drug trials. The findings on endpoint validation are directly applicable to United Kingdom-based MS clinical research and trial design, though they do not address United Kingdom-specific clinical practice or policy.

Key measures

Expanded Disability Status Scale (EDSS) worsening, 9-Hole Peg Test, Timed 25-Foot Walk Test, MRI lesion activity, serum neurofilament light (sNfL), Symbol Digit Modalities Test, Multiple Sclerosis Impact Scale-29

Outcomes reported

The study evaluated composite progression independent of relapse activity (cPIRA) as a clinical trial endpoint in relapsing multiple sclerosis, measuring its characteristics, relationship to biomarkers, sustainability, and predictive value for future disability worsening.

Theme
Measurement & metrics
Subject
Out of scope / non-food
Study type
Research
Study design
Secondary analysis of randomised controlled trial data
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1002/acn3.70111
Catalogue ID
SNmq64coy3-bj9dgm

Topic tags

Pulse AI · ask about this record

Dig deeper with Pulse AI.

Pulse AI has read the whole catalogue. Ask about this record, its theme, or how the findings apply to UK farming and policy — every answer cites the underlying studies.