Inflammation May Be Interventional Target in Primary Progressive Multiple Sclerosis

Inflammatory activity may be modifiable with current licensed DMTs and thus impact long-term disability outcomes in patients with PPMS.

Among patients with primary progressive multiple sclerosis (PPMS), inflammation may contribute to long-term disability and be associated with reduced risk for becoming wheelchair dependent. These study findings were published in JAMA Neurology.

A small proportion of patients with MS present with PPMS (approximately 10%), characterized as detectable disability progression for 1 year or more from onset. There are several disease-modifying treatments (DMTs) available for MS, however, only ocrelizumab has been found to be effective for PPMS at clinical trial.

For this multicenter, observational, retrospective study, data were sourced from the Italian iMedWeb network. Clinical records for patients with PPMS were extracted in November 2018. Risk for wheelchair dependence was evaluated on the basis of DMT treatment and inflammation using a matching approach. Wheelchair dependence was defined as Expanded Disability Status Scale (EDSS) score of 7.0 and inflammation as relapse in the previous 12 months.

The study population comprised 665 patients with PPMS. Over half of patients (55.0%) were women, they were aged mean 47.8 (standard deviation [SD], 10.8) years, disease onset at 43.0 (SD, 10.7) years of age, 52% had supratentorial onset, 45% had spinal cord onset, and first EDSS score was median 4.5 (interquartile range [IQR], 3.5-5.5).

In these patients, DMT exposure may be associated with a decreased risk of becoming wheelchair bound.

Among the matched cohort, 288 received DMTs and 121 did not. Between 16% and 18% of patients had a relapse in the previous 12 months and 36% of both groups had superimposed relapse.

Among the treated cohort, the most common DMTs were interferon-beta (21%) and azathioprine (19%). During the follow-up (mean, 11.1 years), 54% had a moderate effect, 25% switched to highly effective treatment, and 21% started with highly effective treatment. Patients with a higher visit density (P =.001), baseline relapse (P =.003), and higher EDSS scores (P =.003) were more likely to receive DMTs.

At follow-up, more patients who received DMTs had an EDSS score of 7.0 (39% vs 33%) and they reached the score of 7.0 at a younger age (mean, 55.8 vs 57.0 years).

Reaching an EDSS score of 7.0 was associated with superimposed relapse (adjusted hazard ratio [aHR], 2.37; P =.009), DMT therapy (aHR, 1.75; P =.03), and first EDSS score (aHR, 1.32; P <.001). Reduced risk was associated with the interactions between DMT class and starting with highly effective therapy (aHR, 0.31; P =.04), DMT class and switching to highly effective therapy (aHR, 0.32; P =.03), DMT and superimposed relapse (aHR, 0.33; P =.004), DMT class and moderately effective treatment (aHR, 0.41; P =.04), and time dependent DMT and superimposed relapse (aHR, 0.41; P =.01).

Among the subset of patients who did not have relapse in the previous year (n=338), risk for wheelchair dependence was associated with first EDSS score (aHR, 1.28; P =.006) and was inversely related with the interaction between DMT class and starting with highly effective treatment (aHR, 0.34; P =.01).

This study was limited by the low availability of imaging data.

The study authors concluded that “In these patients, DMT exposure may be associated with a decreased risk of becoming wheelchair bound.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Portaccio E, Fonderico M, Iaffaldano P, et al. Disease-modifying treatments and time to loss of ambulatory function in patients with primary progressive Multiple Sclerosis. JAMA Neurol. Published online July 25, 2022. doi:10.1001/jamaneurol.2022.1929