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

Toshinobu Matsui¹, Ryogo Umetsu^1,2, Yamato Kato¹, Yuuki Hane¹, Sayaka Sasaoka¹, Yumi Motooka¹, Haruna Hatahira¹, Junko Abe^1,3, Akiho Fukuda¹, Misa Naganuma¹, Yasutomi Kinosada⁴, Mitsuhiro Nakamura^1✉

1. Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan;
2. Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1, Seiryomachi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan;
3. Medical Database Co., LTD, 3-11-10 Higashi, Shibuya-ku, Tokyo, 150-0011, Japan;
4. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.

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.

Keywords: etanercept, adalimumab, injection site reaction, adverse event reporting system.

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How to cite this article:
Matsui T, Umetsu R, Kato Y, Hane Y, Sasaoka S, Motooka Y, Hatahira H, Abe J, Fukuda A, Naganuma M, Kinosada Y, Nakamura M. 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. Int J Med Sci 2017; 14(2):102-109. doi:10.7150/ijms.17025. Available from http://www.medsci.org/v14p0102.htm