Ocrelizumab and infections

Overview: *Includes patients who received any dose of OCR during the CTP and associated OLE periods of the Phase II (NCT00676715) and Phase III (NCT01247324, NCT01412333, NCT01194570) studies plus VELOCE (NCT02545868), CHORDS (NCT02637856), CASTING (NCT02861014), OBOE (NCT02688985), ENSEMBLE (NCT03085810), LIBERTO (NCT03599245), CONSONANCE (NCT03523858), CHIMES (NCT04377555) and OLERO (NCT05269004), including patients originally randomised to comparator (IFN β-1a or placebo) who switched to open-label OCR treatment (data as of November 2023). Table 1: COVID-19 related AEs were excluded from this analysis, but patients continued to contribute to the incidence of all other AEs. AEs were classified according to MedDRA versions 18.0, 18.1, 22.1 and 24.1. Multiple occurrences of the same AE in one patient are counted multiple times. *Data as of April–July 2015; ^†Includes patients who received any dose of OCR during the CTP and associated OLE periods of the Phase III studies, including patients originally randomised to comparator (IFN β-1a or placebo) who switched to open-label OCR treatment (data as of November 2023); ^‡Includes patients with RMS who received any dose of OCR during the CTP and associated OLE periods of the Phase II (NCT00676715) and Phase III (NCT01247324, NCT01412333) studies plus VELOCE (NCT02545868), CHORDS (NCT02637856), CASTING (NCT02861014), OBOE (NCT02688985), ENSEMBLE (NCT03085810), LIBERTO (NCT03599245), CHIMES (NCT04377555) and OLERO (NCT05269004). Data as of November 2023; ^§Includes patients with PMS who received any dose of OCR during the CTP and associated OLE periods of OBOE (NCT02688985), ORATORIO (NCT01194570), CONSONANCE (NCT03523858) and OLERO (NCT05269004). Data as of November 2023; ^‖SIs are defined using AEs falling into the MedDRA SOC ‘Infections and Infestations’, and using ‘Is the event nonserious or serious?’ from the AE case report form. Figure 1: COVID-19 related AEs were excluded from this analysis, but patients continued to contribute to the incidence of all other AEs. *More information on COVID-19 related SI rates can be found in the supplementary material; ^†Cumulative rates of SIs over a median period of 3.9 years (2016–2019) in a German claims database.⁹ For comparability, the rates were calculated in a subpopulation of patients with RMS and PMS up to the age of 64 years. Post-marketing: *There are well-recognised limitations that should be considered when interpreting spontaneous post-marketing safety reports, including events that may not be causally related to drug exposure; in the real-world setting, events are frequently confounded by factors such as multiple drug use and the presence of pre-existing comorbidities; reporting bias may exist for more significant outcomes, which may result in an overrepresentation of the more serious outcomes; and reporting rates can be stimulated by external factors, such as press reports. The causes of infections are recorded as reported to the company; while the company follows up on all reports to identify the cause, an exact diagnosis is not always possible. Some of the investigations remain ongoing and, therefore, the information may be subject to change. Abbreviations: AE, adverse event; BMI, body mass index; CI, confidence interval; COVID-19, coronavirus disease 2019; CTP, controlled treatment period; DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; IFN β-1a, interferon beta-1a; Ig, immunoglobulin; IR, incidence rate; LLN, lower limit of normal; LRTI, lower respiratory tract infection; MedDRA, Medical Dictionary for Regulatory Activities; OCR, ocrelizumab; OLE, open-label extension; PMS, progressive MS; PPMS, primary progressive MS; PY, patient-years; pwMS, people with MS; RMS, relapsing MS; ROW, rest of world; RR, rate ratio; SI, serious infection; SOC, System Organ Class; UTI, urinary tract infection.