Dupilumab Adverse Events in Nasal Polyp Treatment: Analysis of FDA Adverse Event Reporting System

Abstract

Objectives Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase‐III clinical trials was low, dupilumab‐associated adverse reactions (DAR) with real‐world use is unknown and potentially under‐reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP‐tx) using the FDA Adverse Event Reporting System (FAERS). Study Design Retrospective database study. Methods FAERS was queried for DAR from 2019Q1 to 2021Q2. Individual DAR (iDAR) were categorized and quantitatively compared between treatment groups (CRSwNP, asthma, atopic dermatitis). Zero‐truncated Poisson regression was modeled to predict the number of iDAR, and logistic regression was modeled to predict serious DARs. Results There were 15,411 DAR observations; 911 for CRSwNP‐tx, of which 121 (13.3%) had serious reactions and 3 died. Common CRSwNP‐tx iDAR were dermatologic (13.9%), generalized (13.3%), and injection‐site (10.8%) symptoms. The number of CRSwNP‐tx iDAR was 2.99 [2.81, 3.17], compared to 3.44 [3.32, 3.56] for asthma and 3.18 [3.13, 3.24] for atopic dermatitis (Kruskal‐Wallis test, P < .001). For CRSwNP‐tx, iDAR reported‐risk‐ratio was 0.84 [0.77, 0.92] among men and 1.12 [1.04, 1.22] among older adults (>50). Serious DAR reported‐odds‐ratio was 1.37 [0.91, 2.04] among men and 1.39 [0.93, 2.08] among older adults. Conclusions While there are limitations with FAERS, this analysis suggests CRSwNP‐tx is associated with fewer iDAR compared with other treatment indications. More iDAR are experienced among women and older adults, but men tend to have more serious DAR. Level of Evidence 3 Laryngoscope, 132:2307–2313, 2022

Dupilumab‐induced skin‐associated side effects in patients with chronic rhinosinusitis with nasal polyposis

“…psoriasiform dermatitis, alopecia areata) and rare cases of other diseases 6–8 . A recent report based on the FDA's ‘Adverse Event Reporting System’ found significantly less dupilumab‐related adverse events in patients with CRSwNP as compared to those with AD or asthma 9 . While this study could not further specify adverse skin reactions, series of case reports are describing onset of psoriasiform dermatitis following dupilumab initiation in AD patients 10,11 .…”

“…and co‐workers performed the only prior investigation providing data on dupilumab‐associated dermatologic side effects in CRSwNP patients. While their study included a large number of observations, no details on the nature of dermatologic eruptions were provided 9 . The limited data available in CRSwNP patients is opposed by a multitude of publications reporting either rosacea‐like dermatitis or psoriasiform dermatitis in dupilumab‐treated patients with AD 6,10,11,14 .…”

“…While their study included a large number of observations, no details on the nature of dermatologic eruptions were provided. 9 The limited data available in CRSwNP patients is opposed by a multitude of publications reporting either rosacea‐like dermatitis or psoriasiform dermatitis in dupilumab‐treated patients with AD. 6 , 10 , 11 , 14 In our study, we observed one case of rosacea‐like dermatitis and three cases of psoriasiform dermatitis, with one patient additionally developing alopecia areata.…”

“… 6 , 7 , 8 A recent report based on the FDA's ‘Adverse Event Reporting System’ found significantly less dupilumab‐related adverse events in patients with CRSwNP as compared to those with AD or asthma. 9 While this study could not further specify adverse skin reactions, series of case reports are describing onset of psoriasiform dermatitis following dupilumab initiation in AD patients. 10 , 11 Blocking IL4Rα potentially leads to conversion from Th2‐ to Th1 or Th17‐dominated immune pathways resulting in psoriasis‐ or rosacea‐like skin eruptions.…”

Safety of triazole antifungals: a pharmacovigilance study from 2004 to 2021 based on FAERS

“…It enables quantification of the association between the drug and the reported AEs by signal detection. 15 – 17 In this study, we extracted reports of all triazole antifungal drugs in FAERS between the first quarter of 2004 (first FDA approval) and the third quarter of 2021 (Q3; the latest). Each report in the FAERS database includes information on the following areas: administrative and demographic information and the PRIMARYID; information on the source of the reports; patient outcome information in the case reports; reaction information in the case reports; and medication information in the case reports.…”