Disease-Modifying Therapies Possibly More Beneficial for Relapsed Progressive MS

December 12, 2018

A new analysis has suggested that an inflammatory response may be a crucial and modifiable determinant of disability accrual in progressive-onset multiple sclerosis.

Inflammatory relapse very well may be a crucial—though modifiable—factor in disability accrual in patients with progressive-onset multiple sclerosis (MS), based on the findings of a cohort analysis.1

Investigators from the University of Melbourne, Australia, led by Jordana Hughes, MD, assessed nearly 1500 patients from the prospective international database MSBase, and found that disease-modifying therapies (DMTs), as well as the time patients spent taking them, are capable of preventing disability accrual in patients with progressive-onset MS who have experienced relapse.

The finding inherently advocates for the practice of superimposed relapses in qualified patients with MS, adding more fodder to an already highly-contested discussion surrounding relapses. “This is most likely attributed to differences in natural disease course as well as the preventive association of DMT on relapse-related disability accrual in patients with progressive-onset disease and superimposed relapse,” Hughes and colleagues wrote.

The primary outcome was a confirmed disability progression, based on Expanded Disability Status Scale (EDSS) scores of 1.5 steps in patients with baseline scores of 0; 1 step in patients with baseline scores from 1-5.5; and 0.5 steps in patients with baseline scores of 6 or more.

On average, patients with progressive-relapsing MS (PRMS) were younger than those with primary progressive MS (PPMS), with mean ages of 46 and 51, respectively (Cohen d = .40), and similarly had lower mean EDSS scores (4.0 vs 4.5, Cohen d = .28) at inclusion. Both patient populations had a higher ratio of women to men, and the overall average male patient age was younger (48 years) than in women (50 years).

Investigators found the proportion of follow-up time patients spent on a DMT significantly reduced the risk of confirmed disability progression in patients with relapse (hazard ratio [HR], 0.96; 95% CI: 0.94 - 0.99; P = .01), but not for patients without relapse (HR, 1.02; 95% CI: 0.99 — 1.05; P = .26). Upon accounting for relapse-related progression, the association of DMT in those with superimposed relapse was no longer prevalent (HR, 1.10; 95% CI: 0.96 — 1.24; P = .16).

When incorporating an interaction term between the proportion of time receiving DMT and each patient group into their multivariable model, investigators found that exposure to DMT and the likelihood of confirmed disability progression was dependent on patient allocation to either PPMS or PRMS group (HR, 0.93; 95% CI: 0.90 — 0.97; P <.001).

The 4% relative decrease in hazard of confirmed disability progression events per each 10% increment in persistence receiving DMT observed in patients with PRMS (HR, 0.96; 95% CI: 0.94 — 0.99; P = .01), was not observed in patients with PPMS.

Hughes and her team suggested that the results indicate that relapses represent a positive prognostic marker as a clinical correlate of episodic inflammatory activity. In turn, this means that they could provide clinicians the opportunity to improve MS outcomes by preventing relapse-related disability accrual. Although, this lacks any sort of deep historical context.

Hughes and colleagues elucidated: “Where previous research has identified no difference in age at onset between patients with vs without relapse, we demonstrated that patients with PRMS were younger at disease onset compared with those with PPMS.”

If clinicians were able to distinguish a progressive-onset MS phenotype, they would be identifying patients who may respond to current DMTs, if it were characterized by acute episodic inflammatory changes. The investigators wrote that further research is still necessary for this, and “in particular[,] incorporating evidence of inflammatory magnetic resonance imaging activity as a predictor of disease course.”

A version of this article first appeared on MDMag.com.

REFERENCES

1. Hughes J, Jokubaitis V, Lugaresi A. Association of inflammation and disability accrual in patients with progressive-onset multiple sclerosis. JAMA Neurol. 2018;75(11):1407-1415. doi: 10.1001/jamaneurol.2018.2109.