PND7 - AN EXPLORATORY ANALYSIS OF EFFICACY OF OCRELIZUMAB FOR MULTIPLE SCLEROSIS PATIENTS WITH INCREASED DISABILITY

Three pivotal trials, OPERA I & II and ORATORIO, demonstrated the efficacy of Ocrelizumab (OCR) compared to Interferon Beta-1a (IFN) or Placebo (PLA) in relapsing (RMS) or primary progressive (PPMS) multiple sclerosis patients. We conducted an exploratory subgroup analysis for patients with higher baseline disability from those trials. This was a post hoc data analysis. Patients at the end of the double-blinded randomized controlled treatment period (DB) could enroll in the open-label extension (OLE) by continuing or switching to OCR. Patients were included if their baseline EDSS was >5.0 (RMS) or >6.0 (PPMS). Kaplan-Meier curves and proportional hazards models assessed the effect of treatment on 24-week confirmed disability progression (CDP) (RMS and PPMS), and 20% increase in 9-hole peg test (9HPT) and timed 25-foot walk (T25-FW) (PPMS only). A total of 42 and 50 RMS patients who received OCR and IFN, respectively, and 63 and 25 PPMS patients who received OCR and PLA, respectively, were included. In the DB period, PPMS patients treated with OCR had reduced risks of CDP (HR=0.51, 95% CI: 0.3,1.0), T25-FW (HR=0.55, 95% CI: 0.3,0.9) and 9HPT (HR=0.58, 95% CI: 0.3,1.1). At Week 264 (OLE year 2), 48.6% and 73.5% of OCR/OCR patients had 9HPT and T25-FW worsening, respectively, compared to 84.3% and 91.3% of PLA/OCR patients (9HPT Δ=35.7%, 95% CI: 15.0%, 56.4%; T25-FW Δ=17.8%, 95% CI: 1.2%, 34.3%). RMS patients treated with OCR during the DB period had a reduced risk of CDP (HR=0.29, 95% CI: 0.1,1.4). At Week 240 (OLE year 3), 12.2% of OCR/OCR patients had CDP compared to 27.3% of IFN/OCR patients (Δ=15.2%, 95% CI: -3.3%, 33.6%). PPMS patients with higher disability experienced OCR treatment benefit for CDP, 9HPT and T25-FW. Patients initiating OCR earlier accrued greater and sustained treatment effect compared to patients switching from IFN or PLA.