title: Age-related trends in injection site reaction incidence induced by the tumor necrosis factor-α (TNF-α) inhibitors etanercept and adalimumab: the Food and Drug Administration adverse event reporting system, 2004-2015.
abstract: Tumor necrosis factor-α (TNF-α) inhibitors are increasingly being used as treatment for rheumatoid arthritis (RA). However, the administration of these drugs carries the risk of inducing injection site reaction (ISR). ISR gives rise to patient stress, nervousness, and a decrease in quality of life (QoL). In order to alleviate pain and other symptoms, early countermeasures must be taken against this adverse event. In order to improve understanding of the risk factors contributing to the induction of ISR, we evaluated the association between TNF-α inhibitors and ISR by applying a logistic regression model to age-stratified data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The FAERS database contains 7,561,254 reports from January 2004 to December 2015. Adjusted reporting odds ratios (RORs) (95% Confidence Intervals) were obtained for interaction terms for age-stratified groups treated with etanercept (ETN) and adalimumab (ADA). The adjusted RORs for ETN* ≥ 70 and ADA* ≥ 70 groups were the lowest among the age-stratified groups undergoing the respective monotherapies. Furthermore, we found that crude RORs for ETN + methotrexate (MTX) combination therapy and ADA + MTX combination therapy were lower than those for the respective monotherapies. This study was the first to evaluate the relationship between aging and ISR using the FAERS database.
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan;; Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1, Seiryomachi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
authors.forename: Ryogo
authors.initials: R
authors.lastname: Umetsu
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hane
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sasaoka
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Motooka
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Hatahira
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan;; Medical Database Co., LTD, 3-11-10 Higashi, Shibuya-ku, Tokyo, 150-0011, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Abe
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Akiho
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Naganuma
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kinosada
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects*; D000328:Adult; D000367:Age Factors; D000368:Aged; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D000068800:Etanercept / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007267:Injections / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept
keywords: adalimumab; adverse event reporting system.; etanercept; injection site reaction