Ocrelizumab shorter infusion: Primary results from the ENSEMBLE PLUS substudy in patients with MS

Abstract

Objective: To assess the safety of ocrelizumab (OCR) shorter duration infusion in patients with MS.

Methods: ENSEMBLE PLUS is a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810). In ENSEMBLE, patients with early stage relapsing-remitting MS received OCR 600 mg initially as two 300 mg IV infusions 2 weeks apart and subsequently as a single 3.5-hour 600 mg infusion every 24 weeks for 192 weeks. In ENSEMBLE PLUS, OCR 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration). The primary end point was the proportion of patients with infusion-related reactions (IRRs) after the first randomized dose (assessed during and up to 24 hours postinfusion).

Results: From November 1, 2018, to September 27, 2019, 580 patients were randomized 1:1 to the conventional or shorter infusion group. After the first randomized dose, 67 of 291 patients (23.1%) in the conventional and 71 of 289 patients (24.6%) in the shorter infusion group experienced IRRs. Most IRRs were mild or moderate in both groups; one patient in each group experienced a severe IRR, and in both groups, 98.6% (136 of 138) of all IRRs resolved without sequelae. No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuation occurred. During the first randomized dose, 14 of 291 (4.8%) and 25 of 289 (8.7%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption.

Conclusion: The frequency and severity of IRRs were similar between conventional and shorter OCR infusions. Shortening the infusion time to 2 hours reduces the total infusion site stay time and lessens the overall patient and site staff burden.

Classification of evidence: This interventional study provides Class I evidence that the frequency and severity of IRRs were similar at the first randomized dose using OCR (600 mg) infusions of conventional and shorter duration in patients with relapsing-remitting MS.

Clinical trial identifier number: NCT03085810.