TY - JOUR
T1 - Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors
T2 - An Observational, Pharmacovigilance Study
AU - Le, Thomas K.
AU - Brown, Isabelle
AU - Goldberg, Rebecca
AU - Taylor, Matthew T.
AU - Deng, Junwen
AU - Parthasarathy, Varsha
AU - Bordeaux, Zachary A.
AU - Alphonse, Martin Prince
AU - Kwatra, Madan M.
AU - Naranbhai, Vivek
AU - Gusev, Alexander
AU - Alhariri, Jihad
AU - LeBoeuf, Nicole R.
AU - Reynolds, Kerry L.
AU - Cappelli, Laura C.
AU - Naidoo, Jarushka
AU - Brahmer, Julie R.
AU - Kang, Sewon
AU - Semenov, Yevgeniy R.
AU - Kwatra, Shawn G.
N1 - Funding Information:
The information within VigiBase, the World Health Organization's global database of individual case safety reports, comes from a variety of sources, and the probability that the suspected adverse effect is drug related is not the same in all cases. The authors would like to thank Uppsala Monitoring Center Custom Searches for their help in conducting this study. SGK is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR077073-01A1. LCC received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR075872. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TKL, SGK, and YRS had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This study was conducted in Baltimore, MD. Conceptualization: TKL, JN, YRS, SGK; Data Curation: TKL, YRS, SGK; Formal Analysis: TKL, YRS, SGK; Funding Acquisition: SGK; Investigation: TKL, YRS, SGK; Methodology: TKL, JN, YRS, SGK; Project Administration: YRS, SGK; Resources: TKL, YRS, SGK; Software: TKL, YRS, SGK; Supervision: YRS, SGK; Visualization: TKL, KLR, SGK; Writing – Original Draft Preparation: TKL, RG, MTT, YRS, SGK; Writing – Review and Editing: TKL, IB, RG, MTT, JD, VP, ZAB, MPA, MMK, VN, AG, JA, NL, KR, LCC, JN, JB, SK, YRS, SGK, The findings of this article do not represent the opinion of the Uppsala Monitoring Center or the World Health Organization. The funding to LCC had no involvement in the design or interpretation of this study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
The information within VigiBase, the World Health Organization's global database of individual case safety reports, comes from a variety of sources, and the probability that the suspected adverse effect is drug related is not the same in all cases. The authors would like to thank Uppsala Monitoring Center Custom Searches for their help in conducting this study. SGK is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR077073-01A1. LCC received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR075872. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TKL, SGK, and YRS had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This study was conducted in Baltimore, MD.
Publisher Copyright:
© 2022 The Authors
PY - 2022/11
Y1 - 2022/11
N2 - Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.
AB - Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.
UR - http://www.scopus.com/inward/record.url?scp=85133395518&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2022.04.020
DO - 10.1016/j.jid.2022.04.020
M3 - Article
C2 - 35605659
AN - SCOPUS:85133395518
SN - 0022-202X
VL - 142
SP - 2896-2908.e4
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 11
ER -