Disease-Modifying Therapy More Beneficial In Relapsed Progressive MS Patients

Inflammatory relapse could be a crucial, but modifiable, determinant in disability accrual in patients with progressive-onset multiple sclerosis (MS), according to a new cohort analysis.

In an assessment of nearly 1500 patients in the prospective international database MSBase, investigators from the University of Melbourne, Australia, have found that disease-modifying therapies (DMTs)—and the time patients spent on them—are capable of preventing disability accrual in patients with progressive-onset MS who have experienced relapse.

The finding, which inherently advocates for the practice of superimposed relapses in qualified patients with MS, is more fodder to a 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,” investigators, led by Jordana Hughes, MD, wrote.

In order to analyze the associations between superimposed relapses on the disease outcomes of progressive-onset MS patients, investigators assessed the outcomes of 1419 eligible patients from the MSBases, which has collected data on MS patients since January 1995. Patient inclusion criteria included a primary progressive MS (PPMS) or progressive-relapsing (PRMS) diagnosis, adult-onset, and a minimum data set of at least 3 healthcare visits with the disability recorded, and 3 months between the second and last visit.

Disparity between PPMS and PRMS is noted by the latter group receiving either a diagnosis or having had progressive-onset MS with a record relapse in the data set. Investigators’ primary outcome was a confirmed disability progression event—defined as an increase in Expanded Disability Status Scale (EDSS) scores by 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 PRMS were younger than those with PPMS (mean age, 46 vs 51, Cohen d = .40), and similarly had lower mean EDSS scores (4.0 vs 4.5, Cohen d = .28) at inclusion. A greater ratio of women to men were similar across both patient populations, and overall mean male patient age was younger (48 years) than in women (50 years).

Investigators found the proportion of follow-up time patients spent on DMT significantly reduced the risk of confirmed disability progression in patients with relapse (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). When they accounted for relapse-related progression, the association of DMT in patients 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 MS patient group into their multivariable model, investigators found a more distinct association between therapy and disease course: 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 suggest the findings indicate that relapses represent a positive prognostic marker as a clinical correlate of episodic inflammatory activity. They could provide clinicians the opportunity to improve MS outcomes through the prevention of relapse-related disability accrual.

That said, such findings lack deep historical context.

“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,” investigators explained.

What could have been uncovered is further evidence for a progressive-onset MS phenotype characterized by acute episodic inflammatory changes. If clinicians were able to distinguish such a phenotype, they would be identifying patients who may respond to current DMTs.

“Further research is needed to characterize the role of acute episodic inflammation in progressive-onset disease, in particular incorporating evidence of inflammatory magnetic resonance imaging activity as a predictor of disease course,” they concluded.

The study, "Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis," was published online in JAMA Neurology.