Infections
- PwMS are at greater risk of developing, and being hospitalised for, infections than the general population1–3
- In OCR RMS and PPMS pivotal clinical trials, infections were a frequently reported AE4–6
- However, no increased risk of serious infections with OCR vs IFN β-1a or placebo was observed4–6
- Treatment with OCR in both RMS and PMS populations for longer periods of time was not associated with a higher risk of SIs6
- Over a 10-year follow-up period in clinical trials,* OCR continues to exhibit a stable and favourable safety profile6
Clinical trials (controlled treatment period and open-label extension)
Table 1A: OPERA (RMS) cumulative exposure (controlled treatment period/open-label extension)
Table 1B: ORATORIO (PPMS) cumulative exposure (controlled treatment period/open-label extension)
Table 1C: All RMS, all PMS and OCR all-exposure population
- In PPMS, the rate of SIs remained higher than RMS;6 over time, this could be due to the underlying disease condition (e.g. increasing disability, age, comorbidities)7
Figure 1: Yearly rate of SIs (excluding COVID-19) in RMS* and PMS†
all-exposure populations6
Clinical cut-off date: November 2022
- The majority of SIs were of Grade 3 intensity and were not treatment limiting, with >90% resolved6
- In the RMS and PMS all-exposure populations, UTI and pneumonia were the most commonly reported SIs; this is consistent with incidence rates and patterns observed in real-world studies1,6,8,9
- SI rates remained stable with non-significant year-on-year variation, and within the range reported in real-world registries1,6,8
Figure 2: Yearly rate of SIs (including COVID-19) in RMS* and PMS†
all-exposure populations6
Clinical cut-off date: November 2022
Figure 3: Multivariate model for risk of SIs in OPERA (RMS)10
Clinical cut-off date: January 2020
- Treatment with OCR for longer periods of time was not associated with a higher risk of SIs10
- The presence of ≥2 comorbidities was associated with an increased risk of SIs in people with RMS10
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Figure 4: Multivariate model for risk of SIs in ORATORIO (PPMS)10
Clinical cut-off date: January 2020
- Treatment with OCR for longer periods of time was not associated with a higher risk of SIs10
- Being overweight or obese, having an EDSS >6.0, and having abnormal IgM levels were found to be associated with an increased risk of SIs in people with PPMS10
- For patients who switched to OCR from placebo, a trend towards an increased risk was noted10
As of March 2023:
- 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, excluding COVID-19, were UTI and pneumonia, which is in line with clinical trial data
Overview
*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, CONSONANCE, CHIMES and OLERO including patients originally randomised to comparator (IFN β-1a or placebo) who switched to open-label OCR treatment (data as of November 2022).
Tables 1A, 1B, 1C
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, 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 2022);
‡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;
§Includes patients with RMS 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, CHIMES and OLERO (data as of November 2022);
‖Includes patients with PMS who received any dose of OCR during the CTP and associated OLE periods of ORATORIO, OBOE, CONSONANCE and OLERO (data as of November 2022);
¶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, CONSONANCE, CHIMES and OLERO including patients originally randomised to comparator (IFN β-1a or placebo) who switched to open-label OCR treatment (data as of November 2022).
Figure 1
COVID-19 related AEs were excluded from this analysis, but patients continued to contribute to the incidence of all other AEs.
*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, CHIMES and OLERO (data as of November 2022);
†Includes patients who received any dose of OCR during the CTP and associated OLE periods of OBOE, CONSONANCE and OLERO (data as of November 2022);
‡The exposure in PY during Years 8–11 is limited for meaningful interpretation, so these data are presented in the plots with dotted lines.
Figure 2
*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, CHIMES and OLERO (data as of November 2022);
†Includes patients who received any dose of OCR during the CTP and associated OLE periods of ORATORIO, OBOE, CONSONANCE and OLERO (data as of November 2022);
‡The exposure in PY during Years 8–11 is limited for meaningful interpretation, so these data are presented in the plots with dotted lines.
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.
†From non-interventional post-marketing study and reports from other solicited sources.
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; PMS, progressive MS; PPMS, primary progressive MS; PY, patient-years; pwMS, people with MS; RMS, relapsing MS; ROW, rest of world; SI, serious infection; SOC, System Organ Class; USA, United States of America; 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-ACTRIMS 2023 (Poster P304);
- Hauser SL, et al. Presented at ECTRIMS 2022 (Poster P326);
- Knapp R, et al. Mult Scler Relat Disord 2022;68:104245;
- Persson R, et al. Mult Scler Relat Disord 2020;41:101982;
- Derfuss T, et al. Presented at EAN 2022 (Poster EPO-403);
- Roche data on file.
M-XX-00015937 (Date of preparation: February 2024)