PT  - JOURNAL ARTICLE
AU  - Hauser, Stephen L.
AU  - Kappos, Ludwig
AU  - Montalban, Xavier
AU  - Craveiro, Licinio
AU  - Chognot, Cathy
AU  - Hughes, Richard
AU  - Koendgen, Harold
AU  - Pasquarelli, Noemi
AU  - Pradhan, Ashish
AU  - Prajapati, Kalpesh
AU  - Wolinsky, Jerry S.
TI  - Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis
AID  - 10.1212/WNL.0000000000012700
DP  - 2021 Oct 19
TA  - Neurology
PG  - e1546--e1559
VI  - 97
IP  - 16
4099  - http://n.neurology.org/content/97/16/e1546.short
4100  - http://n.neurology.org/content/97/16/e1546.full
SO  - Neurology2021 Oct 19; 97
AB  - Background and Objectives To 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.Methods Safety 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.Results At data cutoff (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% confidence interval) 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.Discussion Continuous 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 Evidence This 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.AE=adverse event; ALC=absolute lymphocyte count; ANC=absolute neutrophil count; BL=baseline; CI=confidence interval; CTP=controlled treatment period; DMT=disease-modifying treatment; ER=estrogen receptor; IFN=interferon; Ig=immunoglobulin; IRR=infusion-related reaction; LLN=lower limit of normal; MS=multiple sclerosis; NK=natural killer; NMSC=nonmelanoma skin cancer; OCR=ocrelizumab; OLE=open-label extension; PML=progressive multifocal leukoencephalopathy; PPMS=primary progressive multiple sclerosis; PR=progesterone receptor; PwMS=patients with multiple sclerosis; PY=patient-years; RMS=relapsing multiple sclerosis; SAE=serious adverse event; SEER=Surveillance, Epidemiology, and End Results; SI=serious infection; SIR=standardized incidence ratio; UTI=urinary tract infection; W12=week 12