Conventional vs shorter ocrelizumab infusions: which way to go?
In the ENSEMBLE PLUS study, there appears to be no difference in terms of the frequency and severity of infusion-related reactions (IRRs) between the conventional and shorter infusions of ocrelizumab for the treatment of early relapsing-remitting multiple sclerosis (RRMS). However, patients gravitated towards the shorter regimen more than the conventional method.
Within 24 hours of the first randomized dose (RD), IRR rates were similar between the conventional and the shorter infusion arms (27.1 percent vs 28.8 percent).
After unblinding of the study, most patients chose to stay on (n=331) or transition to (n=279) the shorter ocrelizumab infusion. Seventy-one patients in the conventional infusion arm preferred to stay with their regimen, and only 19 from the shorter infusion arm expressed their preference to switch to the conventional regimen. [AAN 2023; abstract P7.003]
ENSEMBLE PLUS was a double-blind substudy of the single-arm ENSEMBLE study which evaluated the safety of a conventional (3.5-hour duration) and a shorter (2.0-hour duration) infusion of ocrelizumab in patients with early RRMS. A total of 745 participants (mean age 34.2 years, 64 percent female) were randomized 1:1 to each arm. Mean time since first symptom was 1.8 years.
Ocrelizumab infusions were administered at a dose of 600 mg every 24 weeks for 192 weeks (up to eight doses) with mandatory premedication. The first dose was administered as per label – two 300-mg infusions 14 days apart.
The majority of IRRs were mild to moderate (grade 1/2) in severity, and none were life-threatening or fatal. Overall, the most frequent IRR symptoms during the first RD were throat irritation (14 percent) and dysphagia (4 percent). The most common IRR symptoms 24 hours post infusion for both regimens were fatigue and headache (12 percent for both).
The frequency of IRRs requiring intervention was low in both the conventional and shorter infusion arms (10.5 percent vs 14.8 percent) and none led to treatment discontinuation. There were also low incidences of infusion interruptions (5.6 percent vs 8.1 percent) and slowing (6.2 percent vs 8.6 percent).
Overall, IRR frequency decreased over the course of RDs, dropping from about 28 percent for both infusion groups at the first RD to 0 percent by the sixth RD. A similar trend was seen among those who had no IRRs prior to the first RD.
“The overall safety profile was similar between arms and in line with the general ocrelizumab safety profile,” said the researchers. Although patient decisions were not strongly driven by the IRRs, most preferred the shorter over the conventional regimen after unblinding.
“Shortening the infusion time to 2 hours reduces total site stay time (including mandatory premedication, infusion, and observation) from 5.5–6.0 hours to 4.0 hours and may reduce patient and site staff burden,” said the researchers.