Infections
- PwMS are at greater risk of developing, and being hospitalised for, infections than the general population1–3
- In clinical trials, infections were a frequently reported AE4,5
- However, no increased risk of serious infections with OCR vs IFN β-1a or placebo was observed4,5
- The COVID-19 pandemic resulted in an increase in the number of cases of infections related to SARS-CoV-2 during the reporting interval6
- The incidence and type of infections seen in the post-marketing setting (data cut-off: March 2022) is in line with the clinical trial data (data cut-off: November 2021)7
Clinical trials (controlled treatment period and open-label extension)
In the OCR all-exposure population, the rate of SIs was consistent with rates of infection-related hospitalisations reported in a real-world MS cohort4–6
Over a 9-year follow-up period, no new (with the exception of COVID-19 type of infections) or unexpected safety signal were seen in patients treated with ocrelizumab in ongoing clinical trials, ocrelizumab continues to exhibit a stable and favourable safety profile6
The most frequently reported SIs overall were consistent with the frequently reported SIs reported for each year4–6
In PPMS, the rate of SIs remained higher than RMS; over time, the underlying disease condition (e.g. increasing disability, age, comorbidities) appears to drive this possible increase4–6
- The majority of SIs were typical in character, resolved, and were not treatment limiting
Figure 1: Yearly rate of SIs in OPERA I/II and ORATORIO populations over 9 years*,6
Figure 2: Multivariate model for risk of SIs in OPERA (RMS)*,7
Figure 3: Multivariate model for risk of SIs in ORATORIO (PPMS)*,7
Tables 1a, 1b, 1c
In the Ex-COVID-19 analysis, 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, except for malignancies.
*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 2020);
‡Includes patients who received any dose of OCR during the CTP and associated OLE periods of the Phase II and Phase III studies plus VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, LIBERTO and CONSONANCE, including patients originally randomised to comparator (IFN β-1a or placebo) who switched to open-label OCR treatment (data as of November 2021);
§Serious infections 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
*The exposure in PY during Year 9 is limited for meaningful interpretation, so these data are presented in the plots with dotted lines.
Figure 2
*Clinical data cut-off: 3 January 2020
Figure 3
*Clinical data cut-off: 3 January 2020
As of March 2022...
- No new findings related to the type or pattern of SIs were identified
- In these post-marketing case reports, the most commonly reported SIs by preferred terms were UTI and pneumonia, which is in line with clinical trial data
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; Ex, excluding; IFN β-1a, interferon beta-1a; IgG, immunoglobulin G; IgM, immunoglobulin M; LLN, lower limit of normal; MedDRA, Medical Dictionary for Regulatory Activities; OCR, ocrelizumab; OLE, open-label extension; PPMS, primary progressive MS; PY, patient-years; pwMS, people with MS; RCT, randomised controlled trial; RMS, relapsing MS; ROW, rest of world; SARS-COV-2, severe acute respiratory syndrome coronavirus 2; SI, serious infection; SOC, System Organ Class; UTI, urinary tract infection.
- Wijnands JMA, et al. Mult Scler 2017;23:1506–16;
- Nelson RE, et al. Int J MS Care 2015;17:221–30;
- Wijnands JMA, et al. J Neurol Neurosurg Psychiatry 2018;89:1050–6;
- Hauser SL, et al. N Engl J Med 2017:376:221–34;
- Montalban X, et al. N Engl J Med 2017;376:209–20;
- Hauser SL, et al. Presented at ECTRIMS 2022 (Poster P326);
- Derfuss T, et al. Presented at EAN 2022 (Poster EPO-403);
- Roche data on file.
M-XX-00012412 (Date of preparation: February 2023)