Safety results of administering ocrelizumab per a shorter infusion protocol in patients with primary progressive and relapsing multiple sclerosis

Abstract

Background: Ocrelizumab is an approved MS treatment administered as two 300-mg intravenous infusions 2 weeks apart (Dose 1), each lasting approximately 2.5 hours, followed by single 600-mg infusions every 6 months lasting approximately 3.5 hours. Our objective was to evaluate shorter-duration ocrelizumab infusions in the Phase IIIb open-label SaROD study (NCT03606460). Methods: Eligible patients received ocrelizumab 600-mg Dose 2 or 3 infused over approximately 2 hours (Cohort 1) or ocrelizumab 300-mg Dose 1, Infusion 2 over approximately 1.5 hours (Cohort 2). The primary endpoint was the number and proportion of patients experiencing Grade 3-4 infusion-related reactions (IRRs) in Cohort 1. Secondary endpoints included Grade 1-4 IRRs in both cohorts and Grade 3-4 IRRs in Cohort 2. Results: Mean infusion times decreased by approximately 1.09 and 0.79 hours in Cohorts 1 and 2, respectively, compared with US prescribing information. IRRs, reported by 36% of 141 patients, were mild-to-moderate, with no observed Grade 3-4 IRRs. No IRR-related discontinuations occurred. No serious AEs, deaths, or new safety signals were observed. Conclusion:The IRR rate with ocrelizumab shorter-duration infusions was similar to that observed in the pivotal Phase III trials. Ocrelizumab can be infused over a shorter time without sacrificing patient safety.

Safety evaluation of shorter infusion for ocrelizumab in a substudy of the Phase IIIb CHORDS trial

“…Reductions may be even greater compared with real‐world data, with some anecdotal evidence suggesting 600‐mg infusions could last as long as 5 to 6 h 12,13 . Importantly, the incidence and severity of IRRs in this substudy were consistent with observations in the pivotal studies, 6 and the overall safety profile was consistent with that seen in ENSEMBLE PLUS 7 and SaROD 8 . Overall, findings demonstrate that the safety profile of OCR remains unchanged with a shorter infusion across different patient populations.…”

“…Reductions may be even greater compared with real-world data, with some anecdotal evidence suggesting 600-mg infusions could last as long as 5 to 6 h. 12,13 Importantly, the incidence and severity of IRRs in this substudy were consistent with observations in the pivotal studies, 6 and the overall safety profile was consistent with that seen in ENSEMBLE PLUS 7 and SaROD. 8 Overall, findings demonstrate that the safety profile of OCR remains unchanged with a shorter infusion across different patient populations. Additional events occurring in one patient (0.8%) each during the 30-day follow-up included skin lacerations, bronchitis, conjunctivitis, ear infection, gastroenteritis, hordeolum, nasopharyngitis, sinusitis, staphylococcal infection, upper respiratory tract infection, band sensation, hypoesthesia, trigeminal neuralgia, visual field defect, influenzalike illness, back pain, abdominal discomfort, dry mouth, cough, upper respiratory tract congestion, ear pain, depression and nephrolithiasis.…”

“…Most IRRs were mild to moderate in severity and decreased with subsequent dosing, [4][5][6] supporting the investigation of shorter OCR infusions. Findings from the Phase IIIb ENSEMBLE PLUS (NCT03085810) 7 and SaROD (NCT03606460) 8 studies, in which patients received one or two doses of OCR as per the initial prescribing recommendations before receiving their next dose as a shorter infusion, demonstrated that a shorter infusion time was not associated with an increased rate or severity of IRRs. [7][8] This article describes outcomes from an extension substudy of CHORDS (NCT02637856), in which patients with relapsing remitting MS (RRMS) who completed four doses of OCR per the initial prescribing recommendations received the scheduled fifth dose over a shorter duration.…”

Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis

“…Results from studies investigating a shorter infusion protocol also indicate that reducing infusion duration does not increase the incidence, patterns, or severity of IRRs. [20][21][22] This may allow improvements in the overall patient experience and optimization of resources at infusion clinics. 23 Real-world studies show an increased risk of infection in PwMS relative to non-MS controls, both in treated and untreated cohorts.…”

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance

“…3 To date, there are 22 disease-modifying therapies (DMTs) available to treat RRMS and active SPMS, with only one approved (ocrelizumab) for PPMS. 4 Unfortunately, this means that many patients with progressive disease have very few treatment options. Research is ongoing to identify biomarkers to detect the transition from RRMS to SPMS, yet this transition still relies primarily on expert opinion.…”