# Real-world effectiveness of high-efficacy therapies in multiple sclerosis: a propensity score-matched cohort study

## TL;DR

High-efficacy MS therapies show better real-world effectiveness and longer treatment persistence compared to low-efficacy options.

## Contribution

Demonstrates real-world effectiveness of high-efficacy MS therapies using a propensity score-matched cohort study.

## Key findings

- High-efficacy DMTs reduced annualized relapse rates by 64% compared to low-efficacy DMTs.
- Treatment discontinuation was 67–87% lower with high-efficacy DMTs.
- Clinical and radiological disease activity was significantly lower with high-efficacy DMTs.

## Abstract

Effectiveness classification of disease-modifying therapies (DMTs) in MS relies either on head-to-head trials or indirect comparisons of annualized relapse rates (ARR) across studies. Validating efficacy estimates in real-world settings is crucial, particularly as the discussion on the broader use of high-efficacy (HE) DMTs including antibodies, S1P receptor modulators, and cladribine tablets, continues to evolve. Because treatment decisions in clinical practice are individualized and no single DMT is universally preferred, effectiveness assessments are appropriately conducted at the group level.

To evaluate the real-world effectiveness of HE vs. low-efficacy (LE) DMTs at the group level.

A retrospective 1:1 propensity score-matched cohort study was conducted using routine data from MS patients initiating HE or LE DMTs at a German tertiary MS center between 2007 and 2023. Primary outcome was ARR; secondary endpoints were cumulative hazard of relapse, MRI activity, loss of NEDA-3, 3-month confirmed disability progression (CDP), and treatment discontinuation.

After matching, 266 datasets were analyzed with a median follow-up of 24 months in the LE DMT group and 43 months in the HE DMT group. ARR was 64% lower with HE DMTs (0.13 vs. 0.37; rate ratio 0.36, 95% –CI: 0.23–0.53; p < 0.001). Relapse hazard, MRI activity, and NEDA-3 loss were 53–63% lower (hazard ratios 0.41, 0.37, and 0.47; all p < 0.001). CDP did not differ between groups. Hazard of treatment discontinuation was 67–87% lower with HE DMTs (hazard ratios 0.13–0.33; all p < 0.001). No discontinuation due to recurrent infections occurred.

HE DMTs resulted in significantly lower clinical and radiological disease activity than LE DMTs in real-world conditions while showing greater treatment persistence. These findings support the broad use of HE DMTs, while LE DMTs may be reserved for specific indications.