DX46
Infusion-Related Reactions with Ocrelizumab in the Phase III Studies
Ocrelizumab (OCR) is an FDA-approved, humanized, CD20+ B cell-selective monoclonal antibody for the treatment of relapsing (RMS) and primary progressive (PPMS) multiple sclerosis. Infusion-related reactions (IRRs) in OCR Phase III studies, including the separate double-blind, double-dummy OPERA I and OPERA II studies (RMS; OCR N=825; comparator: interferon β-1a 44 µg three times weekly; NCT01247324 and NCT01412333) and ORATORIO (PPMS; comparator: placebo; NCT01194570) have been reported.
Objectives:
To define the pattern and characteristics of OCR IRRs in the prespecified pooled analysis of OPERA I and OPERA II, and ORATORIO.
Methods:
OCR recipients received 600 mg intravenously every 24 weeks in OPERA I and OPERA II (96 weeks; first dose: 2×300 mg infusions split by 14 days) and ORATORIO (≥120 weeks; all doses split). Pretreatment per protocol was methylprednisolone (MP) 100 mg intravenous (or equivalent); antihistamines and analgesics/antipyretics were recommended. Populations of interest were those with an IRR (≥1 or >1), a Day 1 IRR (with/without ≥1 later IRRs) and those without Day 1 IRRs with a later IRR. Subgroups were also analyzed by pretreatment.
Results:
Overall, 283 of 825 (34.3%) of OCR recipients in the pooled OPERA analysis had ≥1 IRR; of these, 123 patients (14.9%) had >1 IRR. 227 patients (27.5%) had an IRR on Day 1, of which 106 patients (12.8%) had a further IRR; 56 patients (6.8%) had an IRR after not having an IRR on Day 1. Most IRRs were mild to moderate in severity and generally manageable including by infusion adjustments; one life-threatening IRR (Day 1; bronchospasm; MP alone pretreatment) and no fatal IRRs occurred. 11 patients (1.3%) discontinued due to IRRs. Fewer IRRs were seen in patients pretreated with MP + antihistamines (N=120; ≥1 IRR, 29.2% [n=35]; >1 IRR, 9.2% [n=11]; Day 1 IRR, 19.2% [n=23]) vs other pretreatment groups (≥1 IRR, 31.2–52.6%; >1 IRR, 14.5–21.6%; Day 1 IRR, 24.9–49.5%). ORATORIO study results will be presented.
Conclusions:
IRRs were a common adverse event experienced by 34.3% of patients (≥1 IRR) and most frequently occurred at the first vs later infusions. IRRs were generally mild to moderate in severity, manageable (including infusion adjustments) and less frequent with a combination of premedication with MP + antihistamines before each infusion vs other pretreatment groups.