DMTs may reduce risk for becoming wheelchair dependent in patients with PPMS

In patients with primary progressive MS who experience persistent inflammatory activity, disease-modifying therapies were linked to a reduced risk for becoming wheelchair dependent, according to a study in JAMA Neurology.

“Although several disease-modifying treatments are available for the treatment of relapsing-remitting MS, in the PPMS phenotype, with the exception of ocrelizumab, previous randomized clinical trials of current licensed [disease-modifying therapies] were found to be ineffective,” Emilio Portaccio, MD, of the department of neuroscience, psychology, pharmacology and children’s health at the University of Florence in Italy, and colleagues wrote.

Portaccio and fellow researchers sought to investigate the effectiveness of disease-modifying therapies (DMTs) on the risk for becoming wheelchair dependent in a real-world population of patients with PPMS by conducting a multicenter, observational, retrospective, comparative effectiveness study. They obtained data from the Italian MS register in November 2018 and analyzed it from June to December 2021.

From an initial cohort of 3,298 patients with PPMS, 665 participants (mean age, 43.0 years; 55% women) were included and had at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Of those, 409 were selected for propensity score matching (288 treated, 121 untreated).

Researchers assessed the risk for becoming wheelchair bound (an EDSS score of 7) through multivariable Cox regression models and considered participants who received DMT before reaching a score of 7 treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective).

During the study follow-up, 37% of patients in the matched cohort (152 of 409) reached an EDSS score of 7 after a mean follow-up of 10.6 years. A higher EDSS score at baseline (adjusted hazard ratio = 1.32; 95% CI, 1.13-1.55), superimposed relapses (aHR = 2.37; 95% CI, 1.24-4.54) and DMT exposure (aHR = 1.75; 95% CI, 1.04-2.94) were associated with a higher risk for an EDSS score of 7. Conversely, the interaction interval between DMT and superimposed relapses correlated with a reduced risk for becoming wheelchair bound (aHR = 0.33; 95% CI, 0.16-0.71).

When researchers considered treatment according to DMT class and included DMT as a time-dependent covariate, they reached similar conclusions.

“Results of this comparative effectiveness research study suggest that inflammatory activity is a modifiable risk factor of long-term disability in PPMS,” Portaccio and colleagues wrote. “In these patients, DMT exposure may be associated with a decreased risk of becoming wheelchair bound.”