Comparison of signal detection of tumour necrosis factor-α inhibitors using the Korea Adverse Events Reporting System Database, 2005-2016.

ABSTRACT

OBJECTIVES: There are no pharmacovigilance studies on adverse event (AE) data for tumour necrosis factor alpha (TNFα) inhibitors in South Korea. We analysed AEs induced by adalimumab, infliximab, and etanercept METHODS: We used data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Events Reporting System Database (KIDS-KD) collected between 2005 and 2016. We used three different signal detection methods: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The drug was compared with drug labels in the USA and Korea. Logistic regression analysis identified AEs that are more likely to occur with drug use. RESULTS: Of the 5594 AEs identified, 350, 452, and 71 were related to adalimumab, infliximab, and etanercept, respectively. We identified seven new signals, which were not listed on drug labels in either Korea or the USA, for AEs associated with the study drugs two for adalimumab (medication error and drug failure), two for infliximab (palpitation and temperature sensation change), and three for etanercept (hyperkeratosis, acne, and thyroid neoplasm malignant). Injection site pain (OR 6.14, 95% CI 1.15-32.74) and alopecia (OR 4.54, 95% CI 1.16-17.77) for adalimumab, chest pain (OR 6.01, 95% CI 1.35-26.77) for infliximab, and uveitis (OR 10.11, 95% CI 1.13-90.77) for etanercept were more likely to be reported in patients with each TNFα inhibitor than in those without, respectively. CONCLUSIONS: Seven new signals that were not included in the current label were identified for TNFα inhibitors and should be updated and monitored.Key Points• Large-scale spontaneous AE reporting data and data mining techniques are useful for detecting signals of rare AEs as well as common AEs induced by drugs.• Drug labels should be updated to reflect signals that are newly discovered by continuous monitoring.