POS0708 EVALUATING THE HYPERSENSITIVITY PROFILE OF ANIFROLUMAB AND THE NEED FOR PREINFUSION PROPHYLACTIC TREATMENT IN PATIENTS WITH SLE

Abstract

BackgroundAnifrolumab, a human monoclonal antibody (mAb), is approved in Canada, Japan, and the United States for the treatment of patients with systemic lupus erythematosus (SLE) based on results from the phase 2b MUSE and the phase 3 TULIP-1/-2 trials.1–3 Anaphylactic reactions (ARs), hypersensitivity reactions (HSRs), and infusion-related reactions (IRRs) are risks of mAb infusions, so physicians prescribing anifrolumab may wish to understand the hypersensitivity profile and whether prophylactic pretreatments are required to mitigate HSR/IRRs.ObjectivesTo evaluate the hypersensitivity profile of anifrolumab and the need for pretreatment.MethodsPooled data were analyzed from patients with moderate to severe SLE despite standard therapy who received intravenous infusions (every 4 weeks, 48 weeks) of anifrolumab or placebo in the randomized, 52-week MUSE (NCT01438489),1 TULIP-1 (NCT02446912),2 and TULIP-2 (NCT02446899)3 trials. An AR (analyzed in the anifrolumab 150/300/1000 mg and placebo groups) was defined as acute illness onset within minutes to several hours of infusion with involvement of skin and/or mucosal tissue, and/or respiratory compromise, and/or reduced blood pressure, and/or persistent gastrointestinal symptoms. HSRs and IRRs were analyzed in the anifrolumab 300 mg group (as this is the approved dose) and the placebo group. An HSR was defined as acute illness onset with involvement of skin and/or mucosal tissue during infusion (not meeting the AR definition); IRR was defined as any other reaction occurring during/within 24 hours of infusion. Patients did not receive pretreatment unless they had experienced a previous IRR/HSR in the program. Pretreatment was assumed if a patient received prophylactic antihistamine, corticosteroid, non-steroidal anti-inflammatory drug, and/or dopamine antagonist 1 day before/on the day of infusion.ResultsOf patients who received anifrolumab 300 mg (n=459), anifrolumab 1000 mg (n=105), or placebo (n=466), none experienced ARs; 1 patient who received anifrolumab 150 mg (n=93) experienced an AR. HSRs occurred in 3% (n=12) of anifrolumab 300 mg-treated patients (of whom 4 had a history of HSRs) vs 1% (n=3) in the placebo group. IRRs occurred in 9% (n=43) of anifrolumab-treated patients vs 7% (n=33) in the placebo group. All HSRs and IRRs were mild/moderate in intensity. There were no discontinuations due to HSRs or IRRs in the anifrolumab group, while there were 2 in the placebo group (HSR: n=1; IRR: n=1). In the anifrolumab 300 mg and placebo groups, more patients experienced HSR/IRRs with the initial (1–6) vs later infusions (Figure 1). In the anifrolumab group, the median (median absolute deviation) time to first HSR or IRR was 30.5 (29.5) days or 27.0 (26.0) days, respectively. Of the 12 anifrolumab-treated patients with ≥1 HSR, 3 received subsequent pretreatment, and none had any HSR after the use of pretreatment. Of the 43 anifrolumab-treated patients with ≥1 IRR, 2 received pretreatment, of whom 1 had an IRR after pretreatment and anifrolumab dosage remained unchanged.ConclusionFollowing anifrolumab infusion, ARs were uncommon, and few (3%) patients experienced HSRs. HSRs and IRRs with the approved anifrolumab 300 mg dose were mild to moderate, occurred early in treatment, did not lead to discontinuation, and only rarely required pretreatment. Our data support a safe and manageable hypersensitivity profile for anifrolumab.