Premedication Regimen of Cetirizine, Dexamethasone, and Famotidine Prior to Ocrelizumab Leads to Less Sedation Issues, Study Shows

Preliminary data from a study comparing 2 premedication regimens for ocrelizumab (Ocrevus; Genentech) showed similar frequency and severity of infusion-related symptoms (IRSs); however, a combination of cetirizine, dexamethasone, and famotidine (C-PO) had a significantly lesser effect on sedation. These data showed that C-PO can be a safe and effective premedication regimen for patients with multiple sclerosis (MS) pursuing ocrelizumab.¹

The study, presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29-June 1 in Nashville, Tennessee, pinned 2 premedication regimens against each other: oral diphenhydramine 50 mg, intravenous (IV) dexamethasone 20 mg, and oral famotidine 20 mg (D-IV) vs C-PO in 50 patients with MS. Because the prescribing information for ocrelizumab recommends premedication with IV corticosteroid and an antihistamine to reduce IRSs, the study aimed to see whether one approach may be more advantageous in the frequency of sedation, IRSs, and pre-infusion-related adverse events (AEs) before, during, and after administration.

As of April 3, 2024, 50 patients with MS completed at least 1 cycle of ocrelizumab 600 mg with premedication D-IV, and of these, 31 patients completed an additional subsequent cycle of ocrelizumab 600 mg with premedication C-PO. Led by senior author Joshua Katz, MD, co-director of The Elliot Lewis Center For Multiple Sclerosis Care, participants were asked at each cycle to complete a questionnaire regarding drowsiness and related symptoms prior to administration of premedications, immediately after cycle, and 24 hours after cycle.

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In total, 34 of 50 patients (68.0%) reported IRSs with D-IV and 21 of 31 patients (67.7%) reported IRSs with C-PO. Similar results were found for moderate to severe IRSs, as 20% (n = 10) of patients with D-IV reported at least 1 vs 19.4% (n = 6) with C-PO. The biggest difference between the 2 treatment approaches was with sedation. Results showed that 86% (n = 43) of patients reported being less alert with D-IV compared with 38.7% (n = 12) with C-PO. Additionally, 48% (n = 24) experienced moderate to severe decreased alertness with D-IV compared with 12.9% (n = 4) with C-PO.

Ocrelizumab, a second-generation anti-CD20 recombinant monoclonal antibody, is the only approved therapy for patients with progressive forms of MS. The therapy is initially given as a 300 mg IV infusion over 2.5 hours, followed up with an additional 300 mg IV infusion 14 days later. Subsequent doses are given every 6 months as a 600 mg IV infusion over 3.5 hours.

The therapy is contraindicated in patients with a history of life-threatening infusion reactions and those with active hepatitis-B infection. Before initiating ocrelizumab, patients are expected to have all necessary immunizations given at least 6 weeks prior, given the expected B-cell depletion.

One previous 2019 study, published in the journal of Multiple Sclerosis Related Disorders, showed that a regiment of cetirizine (10 mg), randitidine (75 mg), increased hydration, IV diphenhydramine (50 mg), IV methylprednisolone (125 mg), and oral acetaminophen (650 mg), was shown to reduce infusion reactions by 60%. The analysis, which included 207 patients receiving ocrelizumab, showed a significant reduction of infusion-association reactions with increasing age (OR, 0.94; P = .001) and male sex (OR, 0.34; P = .034).²

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REFERENCES
1. Fearey M, Greenawalt P, Stine S, et al. Tolerability of Oral Cetirizine and Oral Dexamethasone vs Oral Diphenhydramine and Intravenous Dexamethasone in Patients Treated With Ocrelizumab. Presented at: 2024 CMSC Annual Meeting; May 29-June 2; ABSTRACT LB08
2. Conte WL, Arndt N, Cipriani VP, Dellaria A, Javed A. Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol. Mult Scler Relat Disord. 2019;27:397-399. doi:10.1016/j.msard.2018.11.027