PMID- 31694698 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20200713 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 7 IP - 1 DP - 2019 Nov 6 TI - Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system. PG - 286 LID - 10.1186/s40425-019-0754-2 [doi] LID - 286 AB - BACKGROUND: Immune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment of a broad spectrum of malignancies. ICIs can produce durable antitumor responses but they are also associated with immune-related adverse events (irAEs). Endocrinopathies have reported as one of the most common irAEs of ICIs. METHODS: This study aimed to quantify association of endocrine adverse events (AEs) and ICI therapy and also to characterize the profiles of ICI-related endocrine complications from real-world practice. Data from the first quarter of 2014 to first quarter of 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered to conduct disproportionality analysis. The definition of endocrine AEs relied on the preferred terms (PTs) provided by the Medical Dictionary for Regulatory Activities (MedDRA). Two signal indices based on statistical shrinkage transformation, reporting odds ratios (ROR) and information component (IC), were used to evaluate correlations between ICIs and endocrine events. For ROR, it was defined a signal if the lower limit of the 95% confidence interval (ROR(025)) more than one, with at least 3 cases. For IC, lower end of the 95% confidence interval of IC (IC(025)) exceeding zero was deemed statistically significant. RESULTS: A total of 29,294,336 records were involved, among these 6260 records related to endocrine AEs after ICIs treatment were identified. In general, male had a slightly lower reporting frequencies for ICIs-related endocrinopathies compared with female but not significant (ROR = 0.98 95%CI: 0.93-1.04) and the difference varied in several common endocrine AEs. Notably, in general, ICI drugs were significantly associated with over-reporting frequencies of endocrine complications, corresponding to IC(025) = 2.49 and ROR(025) = 5.99. For monotherapy, three strategies (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing endocrine events. Different reporting frequencies emerged when anti-CTLA-4 therapy was compared with anti-PD-1/PD-L1 medications for endocrine toxicities, corresponding to ROR = 1.68 (95%CI 1.55-1.83), ROR = 2.54 (95%CI 2.20-2.93), respectively. Combination therapy was associated with higher risk of endocrinopathies compared with monotherapy (ROR = 2.00, 95%CI 1.89-2.11). When further analysis, the spectrum of endocrine AEs differed in immunotherapy regimens. Hypothyroidism (N = 885,14.14%), adrenal insufficiency(N = 730,11.66%), hypophysitis (N = 688,10.99%) and hyperthyroidism (N = 472,7.54%) were top 4 ranked endocrine events after ICI therapy and their reporting frequency also differed in ICI immunotherapies. CONCLUSION: Our pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice. FAU - Zhai, Yinghong AU - Zhai Y AD - Tongji University School of Medicine, 1239 Siping Road, Yangpu District, Shanghai, 200092, China. AD - Department of Health Statistics, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China. FAU - Ye, Xiaofei AU - Ye X AD - Department of Health Statistics, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China. FAU - Hu, Fangyuan AU - Hu F AD - Department of Health Statistics, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China. FAU - Xu, Jinfang AU - Xu J AD - Department of Health Statistics, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China. FAU - Guo, Xiaojing AU - Guo X AD - Department of Health Statistics, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China. FAU - Zhuang, Yonglong AU - Zhuang Y AD - Beijing Bioknow Information Technology Co.Ltd., Beijing, China. FAU - He, Jia AU - He J AUID- ORCID: 0000-0002-2338-9501 AD - Tongji University School of Medicine, 1239 Siping Road, Yangpu District, Shanghai, 200092, China. hejia63@yeah.net. AD - Department of Health Statistics, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China. hejia63@yeah.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191106 PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Endocrine Disruptors) SB - IM MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents, Immunological/*adverse effects/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Databases, Factual MH - Drug-Related Side Effects and Adverse Reactions/diagnosis/*epidemiology MH - Endocrine Disruptors/*adverse effects/therapeutic use MH - Female MH - Humans MH - Male MH - *Mandatory Reporting MH - Middle Aged MH - Neoplasms/*complications/drug therapy/*epidemiology MH - Pharmacovigilance MH - Retrospective Studies MH - United States MH - United States Food and Drug Administration PMC - PMC6836403 OTO - NOTNLM OT - CTLA-4 OT - Combination therapy OT - Endocrine toxicities OT - FAERS OT - Immune checkpoint inhibitors OT - Monotherapy OT - PD-1/PD-L1 COIS- Not applicable. EDAT- 2019/11/07 06:00 MHDA- 2020/07/14 06:00 PMCR- 2019/11/06 CRDT- 2019/11/08 06:00 PHST- 2019/07/14 00:00 [received] PHST- 2019/09/20 00:00 [accepted] PHST- 2019/11/08 06:00 [entrez] PHST- 2019/11/07 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] PHST- 2019/11/06 00:00 [pmc-release] AID - 10.1186/s40425-019-0754-2 [pii] AID - 754 [pii] AID - 10.1186/s40425-019-0754-2 [doi] PST - epublish SO - J Immunother Cancer. 2019 Nov 6;7(1):286. doi: 10.1186/s40425-019-0754-2.