The impact of anti-TNFα agents on weight-related changes: new insights from a real-world pharmacovigilance study using the FDA adverse event reporting system (FAERS) database

ABSTRACT

Introduction

Studies in patients with immune-mediated inflammatory diseases (IMIDs) have inconsistently suggested that anti-TNFα therapy may be associated with excessive weight gain.

Areas covered

We performed a nested case/non-case analysis to investigate the anti-TNF-α inhibitor-associated body-changes in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The risk was expressed as a measure of disproportionality using the reporting odds ratio (ROR) while adjusting for sex, drugs known to cause weight gain and reporter type. We also performed a time-to-onset (TTO) analysis of body weight-related events.

Results

Infliximab was the most commonly involved TNF-α inhibitor in body weight-related changes, reaching an aROR of 1.42 (95%CI:1. 26; 1.59). An increased risk was especially found in patients affected by rheumatic disorders, both in the adult and pediatric population. The median TTO after the start of anti- TNFα therapy was about 6–7 months for both children and adults.

Conclusions

Given the potential effect of these agents on the excess weight gain in IMIDs patients, continuous attention for this side effect with appropriate counseling regarding lifestyle modifications are warranted, especially in those at high risk for obesity.

KEYWORDS:

• Body weight
• pharmacovigilance
• anti-TNF-alpha agents
• immune-mediated inflammatory diseases

Declaration of interest

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RPvM is an employee of Oracle Health Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

FM conceptualized and designed the study, interpreted the data drafted the manuscript, revised and approved the final manuscript as submitted. BV, M AB, A S, P M, M G, and G M, R P. van M, participated in the conceptualization and design of the study, participated in the analysis and interpretation of the data, revised the article, and approved the final article as submitted. R S and E C participated in the conceptualization and design of the study, participated in the analysis and interpretation of the data, coordinated and supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted. CC conceptualized and designed the study, interpreted the data, coordinated and supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the Regional Center of Pharmacovigilance of Lombardy (to EC), the Italian Medicines Agency, Agenzia Italiana del Farmaco (AIFA, to EC), and by the Italian Ministry of Health (Ricerca Corrente 2019-2020, to MP; and Progetto Finalizzata RF-2016-02363761 to EC) which are gratefully acknowledged. The funding public institutions had no role in any part of the work. FM is enrolled in the PhD in Experimental and Clinical Pharmacological Sciences, University of Milano, which supports his fellowship.