Duration of disease-modifying treatment impacts disability outcomes in MS

Longer exposure to disease-modifying treatment delayed the time to wheelchair use among patients with primary progressive MS, or PPMS, according to findings presented at MSVirtual2020.

Additionally, treating younger patients — and a decrease in the delay of time to treatment — improved patients’ long-term disability outcomes, study findings showed.

“Previous phase 3 randomized, controlled trials and real-world studies largely failed to find benefit of disease-modifying drugs among patients affected by primary progressive MS,” Mattia Fonderico, a PhD candidate at the University of Florence in Italy, said during his presentation. “Most of the real-world studies draw the same conclusion, finding no substantial differences between treated and untreated patients. However, some recent results highlighted that sustained exposure to disease-modifying treatments, especially when the drug is administered closer to the disease onset and at a younger age, may serve a protective role, reducing the risk of hard disability milestones.”

Fonderico and colleagues used the Italian MS Registry to identify patients with primary progressive MS (PPMS). The study aimed to determine the effect of disease-modifying treatments (DMTs) on becoming wheelchair-dependent.

The researchers included patients with at least three Expanded Disability Scale Status, or EDSS, evaluations and 3 years of follow-up. They defined study baseline as the first EDSS evaluation for untreated patients and the date of the first DMT initiation for treated patients.

Fonderico and colleagues assessed the impact of DMT on reaching EDSS 6 or 7 as a dichotomous variable (yes or no) and as a time-dependent covariate through multivariable Cox regression models adjusted for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate and annualized relapse rate. They compared outcomes with an as-treated analysis and used propensity-score matching to identify cohorts with similar baseline characteristics. They also evaluated DMT exposure in terms of quartiles of exposure.

The final study cohort of 1,214 patients included 671 women, with a mean baseline age of 48.7 (± 11.1) years and a mean EDSS score of 4.1 (± 1.8). Sixty-five percent of the study population received a DMT in the follow-up period.

At a mean follow-up point of 11.6 (± 6.3) years, 994 patients (82%) achieved EDSS6; 539 patients ( 44%) achieved EDSS7. Multivariable regression models demonstrated the use of DMT — when analyzed as a dichotomous variable — did not impact the risk for reaching EDSS 6 (adjusted HR [aHR] = 1.1; 95% CI, 0.95-1.28) and EDSS 7 (aHR = 0.93; 95% CI, 0.77-1.12).

However, Fonderico and colleagues found that greater DMT exposure significantly decreased the risk for reaching EDSS 7 (aHR = 0.73; 95% CI, 0.56-0.95). Patients in the upper quartile of DMT exposure, compared with those with less DMT exposure, were younger at baseline (mean age, 44.1 ± 10.6 years; P < .001) and treated with the first DMT closer to disease onset (mean time to first DMT, 6.8 ± 6.1 years; P = .002). The researchers confirmed these findings in the propensity-score matching analysis.

“In our cohort, treatment persistence delayed time to wheelchair in patients with PPMS,” Fonderico said. “Our analysis suggested that treating younger patients and reducing delays to treatment initiation may improve patients’ long-term disability outcomes.”

Future studies should evaluate long-term safety to maximize the risk-benefit balance and determine whether — and at what point — it is of no value to continue a DMT in PPMS, Fonderico added.

“Real-world studies will be crucial in assessing long-term safety in order to maximize the benefit-risk balance,” he said.