Author Of 1 Presentation
SS02.05 - COVID-19 in persons with multiple sclerosis treated with ocrelizumab: pharmacovigilance update
Limited evidence-based data exist on potential risks of COVID-19 infection in persons with multiple sclerosis (pwMS) receiving immunotherapy. More than 160,000 pwMS have been treated with ocrelizumab (OCR), in clinical trial and real-world settings; data continue to show a consistent and favorable benefit/risk profile.
To present a summary of postmarketing pharmacovigilance data (as of May 31, 2020) from pwMS treated with OCR, who have either confirmed or suspected COVID-19.
Pharmacovigilance-reported adverse event (AE) COVID-19 cases, identified in a search of the Roche Global Safety Database using MedDRA preferred terms and string searches, were defined as valid when at least an identifiable reporter, a single identifiable patient, a medicinal product and a suspected AE were provided. Cases were designated as serious if described by the reporter as serious according to their judgment or if adjudicated as serious by the company when regulatory definitions were met. Patient characteristics and details of OCR treatment were usually provided. All cases were conservatively considered as having confirmed COVID-19. Outcome was classified as recovered, recovering, not recovered, fatal, or not reported.
Of 201 cases, 61% (n=122/201) were reported as non-serious, and 39% (n=79/201) were reported as serious, mostly due to hospitalization (n=51/79). Where known, reasons for hospitalization included, among others, treatment of pneumonia and treatment in ICU. Serious cases were reported as recovered/recovering in 32% (n=25/79) of patients, whilst the outcome was not reported in 33% (n=26/79) of serious cases. A fatal outcome was reported in 5.5% (n=11/201) of patients; risk factors included hypertension, diabetes mellitus, respiratory disease, and malignancy. Updated assessment of the pharmacovigilance cases will be presented.
Taking into account the known limitations of postmarketing safety data, this analysis appears to be in line with published larger case series of non-MS and MS COVID-19 patients. Risk factors in fatal cases were similar to known risk factors reported in the general population.
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.