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

Bermel, Robert; Waubant, Emmanuelle; Pardo, Gabriel; Bass, Ann D; Repovic, Pavle; Newsome, Scott D.; Lindsey, J. W.; Kile, Deidre; Pradhan, Ashish; Musch, B; Zabeti, Aram

doi:10.1002/acn3.51310

Cited by 8 publications

(11 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

ObjectiveTo report safety of ocrelizumab (OCR) up to 7 years in patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) enrolled in clinical trials or treated in real-world postmarketing settings.MethodsSafety analyses are based on integrated clinical and laboratory data for all patients who received OCR in 11 clinical trials, including the controlled treatment and open-label extension (OLE) periods of the phase 2 and 3 trials, plus the phase 3b trials VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, CONSONANCE, and LIBERTO. For selected adverse events (AEs), additional postmarketing data were used. Incidence rates of serious infections (SIs) and malignancies were contextualized using multiple epidemiologic sources.ResultsAt data cut-off (January 2020), 5,680 patients with multiple sclerosis (MS) received OCR (18,218 patient years [PY] of exposure) in clinical trials. Rates per 100 PY (95% CI) of AEs (248; 246–251), serious AEs (7.3; 7.0–7.7), infusion-related reactions (25.9; 25.1–26.6), and infections (76.2; 74.9–77.4) were similar to those within the controlled treatment period of the phase 3 trials. Rates of the most common serious AEs, including SIs (2.01; 1.81–2.23) and malignancies (0.46; 0.37–0.57), were consistent with the ranges reported in epidemiologic data.ConclusionContinuous administration of OCR for up to 7 years in clinical trials, as well as its broader use for more than 3 years in the real-world setting, are associated with a favorable and manageable safety profile, without emerging safety concerns in a heterogeneous MS population.Classification of evidenceThis analysis provides Class III evidence that long-term, continuous treatment with OCR has a consistent and favorable safety profile in patients with RMS and PPMS. This study is rated Class III because of the use of OLE data and historical controls.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Specifically, minimizing treatment burden for patients could help to increase patient satisfaction and adherence, while reducing the time required at the infusion center may lower treatment cost and lead to decreased workloads for infusion site staff, optimizing resource use (Pritchard et al, 2014;Sehn et al, 2007;Tuthill et al, 2009). The safety and tolerability of shorter ocrelizumab infusions are being investigated in a number of studies (Hartung et al, 2020;Bermel et al, 2019;Vollmer et al, 2019). Here, we describe findings from SaROD (ShoRter Ocrelizumab infusion stuDy; NCT03606460), an open-label, nonrandomized, Phase IIIb study evaluating the safety and tolerability of shorter-duration 300-and 600-mg ocrelizumab infusions in patients with RMS or PPMS.…”

Section: Introductionmentioning

confidence: 99%

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

Vollmer

Cohen

Alvarez

et al. 2020

Multiple Sclerosis and Related Disorders

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…In each group, the majority of IRRs were mild or moderate in severity and resolved without sequelae; no IRRs led to treatment discontinuation and there were no serious, life-threatening or fatal IRRs in either group [ 33 ]. The results of ENSEMBLE PLUS were supported by those of the CHORDS extension substudy ( n = 129 with RRMS) [ 39 ] and the US open-label, phase IIIb SaROD shorter infusion study, which included several patients with PPMS (representing 9.5% of the 95 patients with MS in the shorter 600 mg infusion cohort) [ 34 ].…”

Section: Tolerability Of Ocrelizumabmentioning

confidence: 83%

Ocrelizumab: A Review in Multiple Sclerosis

Lamb

2022

Drugs

View full text Add to dashboard Cite

Ocrelizumab (Ocrevus ® ) is an intravenously administered, humanized anti-CD20 monoclonal antibody approved for the treatment of adults with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS). The efficacy of ocrelizumab in reducing relapse rates and disease activity in patients with RMS was demonstrated in pivotal trials (versus interferon β-1a) and supporting single-arm studies in specific subpopulations. In patients with PPMS, ocrelizumab reduced measures of clinical and MRI progression relative to placebo. Clinical benefits were maintained over ≥ 7.5 study years of treatment. Ocrelizumab was generally well tolerated and no new safety signals have emerged with long-term use. Extensive (albeit short-term) real-world data pertaining to ocrelizumab is consistent with that from clinical trials. Ocrelizumab provides the convenience of short, half-yearly infusions. Ocrelizumab continues to represent a generally well-tolerated, high-efficacy disease-modifying therapy (DMT) for RMS and is a valuable treatment for delaying disease progression in patients with PPMS (for whom there are currently no other approved DMTs). Supplementary Information The online version contains supplementary material available at 10.1007/s40265-022-01672-9.

show abstract

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

Cited by 8 publications

References 8 publications

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

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

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

Ocrelizumab: A Review in Multiple Sclerosis

Contact Info

Product

Resources

About