Comparison of Adverse Event Profiles of Tumor Necrosis Factor-Alfa Inhibitors: Analysis of a Spontaneous Reporting Database

Abstract

Tomohito Wakabayashi, Keiko Hosohata, Saki Oyama, Ayaka Inada, Sayaka Ueno, Hiroko Kambara, Tatsuya Iida, Takahiro Nakatsuji, Mayako Uchida, Kazunori Iwanaga Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, JapanCorrespondence: Keiko HosohataEducation and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, JapanTel [phone]Fax [phone]Email [email protected]: Concerns over safety profiles of tumor necrosis factor (TNF)-alfa inhibitors have been raised. The purpose of this study was to clarify the adverse events associated with TNF-alfa inhibitors using a spontaneous reporting system database.Materials and Methods: A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between 2004 and 2017 were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated.Results: Among the 34,031 reports of adverse events associated with TNF-alfa inhibitors, 65.8% were women, who were frequently in their 60s (28.2%). Signals were detected for pneumonia (ROR, 5.36; 95% CI, 5.14– 5.6), interstitial lung disease (ROR, 2.04; 95% CI, 1.95– 2.15), pneumocystis jirovecii pneumonia (ROR, 11.8; 95% CI, 11.1– 12.5), and herpes zoster (ROR, 6.4; 95% CI, 5.92– 6.91) for TNF-alfa inhibitors as a class. There was variability in their signal strength across individual TNF-alfa inhibitors.Conclusion: The strength of the associations of TNF-alfa inhibitors with adverse events is variable, and further studies are required to evaluate the identified signals.Keywords: TNF-alfa inhibitors, adverse drug events, spontaneous reporting system, reporting odds ratio, Japanese Adverse Drug Event Report database

Keywords

• tnf-alfa inhibitors
• adverse drug events
• spontaneous reporting system
• reporting odds ratio (ror)
• japanese adverse drug event report (jader) database