Ocrelizumab in Patients With Early-stage RRMS—Results from the Phase IIIb ENSEMBLE Trial and the Matched Real-world NTD MS Registry Cohort
Hans-Peter Hartung1, Trygve Holmoy2, Jens Wuerfel3, Yanic Heer4, Stefan Braune5, Arnfin Bergmann5, Mel Zuercher4, Sabrina Guye6, Thomas Kuenzel6, Suzanne Moore6, Timothy Vollmer7
1Department of Neurology, UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University, 2Department of Neurology, Akershus University Hospital, 3Roche PDMA Neuroscience, 4Neurology Department, PricewaterhouseCoopers AG, 5NeuroTransData, 6F. Hoffmann-La Roche Ltd., 7University of Colorado
Objective:
To contextualize ocrelizumab effectiveness in early-stage relapsing-remitting multiple sclerosis (RRMS) from the multicenter, open-label, single-arm, Phase IIIb ENSEMBLE trial (NCT03085810) with real-world, first-line disease-modifying therapies (DMTs), using the German NeuroTransData (NTD) MS registry
Background:
Early treatment with high-efficacy DMTs can provide long-term benefits on MS disease outcomes. Understanding of ocrelizumab effectiveness in early-stage MS is still limited.
Design/Methods:
Treatment-naive patients with early-stage RRMS from ENSEMBLE receiving ocrelizumab were matched to NTD intent-to-treat (ITT) patients initiating interferon β-1a/-1b, glatiramer acetate, dimethyl fumarate and teriflunomide as index therapies. We applied propensity-score methods targeting a 2:1 matching ratio, controlling for seven baseline covariates, including brain-imaging activity. No evidence of disease activity (NEDA-2; including no relapses or 24-week confirmed disease worsening [CDW]) up to 120 weeks was explored as an efficacy outcome.
Results:
Overall, 301 ENSEMBLE patients were matched to 198 NTD–ITT patients. Baseline covariates were similar and well-balanced post-matching (standardized mean difference <0.2). The number of patients achieving NEDA-2 at Week 120 was 238 (79.1%) and 122 (61.6%) in the matched ENSEMBLE and NTD–ITT cohorts, respectively. The odds ratio (OR; 95% CI) comparing ENSEMBLE versus NTD–ITT cohort for NEDA-2 were 2.30 (1.50–3.52), primarily driven by an effect on relapses whereas there was no significant effect on 24-week CDW. Treatment switches including to high-efficacy DMTs occurred across the treatment pathways in NTD–ITT cohort.
Conclusions:
Ocrelizumab in early RRMS was associated with significantly lower risk of disease activity assessed by NEDA-2 compared with real-world treatment pathways including first-line DMTs. The study is limited by the short observation period while non-disabling relapses are frequent in early RRMS. The ITT approach accounted for the real-world treatment pathways and DMT switches; however, it may not fully account for the effect on disability worsening of escalation strategy to high-efficacy DMTs applied in NTD.