Author Of 1 Presentation
P0237 - Sustained reduction in 48-week confirmed disability progression in patients with PPMS treated with ocrelizumab in the ORATORIO OLE: 7-year follow-up (ID 109)
The efficacy and safety of ocrelizumab (OCR) in primary progressive multiple sclerosis were demonstrated vs placebo (PBO) in the Phase III ORATORIO study (NCT01194570).
To assess the efficacy of switching to or maintaining OCR therapy on 48-week confirmed disability progression (CDP), in the open-label extension (OLE) of ORATORIO, over 7 years (360 weeks).
In the double-blind period (DBP), patients were randomized to OCR or PBO and followed for ≥120 weeks until a prespecified number of CDP events occurred. At DBP completion, patients remained on blinded treatment until the trial outcome was determined (extended controlled period; ECP). At OLE start, patients continued OCR (OCR-OCR) or switched from PBO to OCR (PBO-OCR). Time to 48-week CDP-EDSS (Expanded Disability Status Scale [EDSS] score increase from baseline [BL] of ≥1 point if BL EDSS ≤5.5 or ≥0.5 points if BL EDSS >5.5), time to 48-week CDP on the 9-Hole Peg Test (CDP-9HPT; ≥20% increase from BL in timed 9HPT) and time to 48-week confirmed EDSS≥7 (wheelchair requirement) are presented up to Week 360.
Overall, 72% of patients entered the OLE. At Week 168 (12 weeks after the first patients entered the OLE), the proportion of patients with 48-week CDP-EDSS in the PBO-OCR and OCR-OCR groups was 44.4% vs 30.5% (Δ=13.9%; p<0.001), respectively; at Week 360 the corresponding proportions were 65.7% vs 54.2% (Δ=11.6%; p=0.006). At Week 168, the proportion of patients with 48-week CDP-9HPT in the PBO-OCR and OCR-OCR groups was 27.9% vs 15.8% (Δ=12.1%; p<0.001); at Week 360 the corresponding proportions were 41.6% vs 31.1% (Δ=10.6%; p=0.014), respectively. At Week 168 the proportion of patients with 48-week confirmed EDSS≥7 in the PBO-OCR and OCR-OCR groups was 9.1% vs 4.8% (Δ=4.3%; p=0.054), respectively; at Week 360 the proportions were 21.7% vs 12.3% (Δ=9.4%; p=0.009). During the DBP+ECP+OLE, compared with the PBO-OCR group, continuous OCR treatment reduced the risk of CDP-EDSS by 31% (HR [95% CI]: 0.69 [0.56–0.86]; p<0.001), CDP-9HPT by 34% (HR [95% CI]: 0.66 [0.50–0.87]; p=0.003) and 48-week confirmed EDSS≥7 by 44% (HR [95% CI]: 0.56 [0.37–0.85]; p=0.006). Timed 25-Foot Walk, composite CDP and 24-week CDP will also be presented. The OLE safety profile was consistent with the DBP.
After 7 years, 48-week CDP outcomes favoured those on earlier and continuous OCR treatment. Patients initiating OCR 3–5 years earlier had a significantly reduced risk of requiring a wheelchair vs those switching from PBO.