Clinical trials in non-ambulatory people with progressive multiple sclerosis: can the nine hole peg test step up as primary outcome measure?

Background Non-ambulatory patients are generally excluded from clinical trials in progressive multiple sclerosis (MS), even though they continue to experience disability worsening. Using hand function - assessed with the Nine Hole Peg Test (NHPT) - as a primary endpoint could enable their inclusion. We aimed to describe two-year NHPT trajectories and identify predictors of worsening in this population to inform the design of such trials.Methods We included 131 patients from the Belgian National MS Center (Melsbroek) database with (1) progressive MS, (2) a baseline Expanded Disability Status Scale (EDSS) score of ≥ 7.0, and (3) available NHPT and EDSS scores at baseline, 12, and 24 months. We applied four definitions for NHPT worsening: classical (C), best hand (BH), worst hand (WH), and either hand (EH). We investigated associations between baseline characteristics and NHPT worsening with logistic regression.Results Across all four definitions, NHPT performance consistently worsened over time. C, BH, and WH outcomes showed similar progression rates: approximately 25% at 12 months and 40% at 24 months. The EH-NHPT definition proved most sensitive (35.9% worsening at 12 months and 52.7% at 24 months), with paradoxical improvement observed in 15.3% and 9.2% of patients, respectively. Older age and poor hand function at baseline modestly decreased the likelihood of EH-NHPT worsening at 24 months; there were no significant predictors at 12 months.Conclusion Hand function deteriorates in non-ambulatory people with progressive MS. The EH-NHPT may represent a sensitive and feasible endpoint for future clinical trials in this often-neglected population.