Comparison of post-marketing surveillance approaches regarding infections related to tumor necrosis factor inhibitors (TNFi’s) used in treatment of autoimmune diseases

ABSTRACT

Objectives: To examine agreement between the FDA Adverse Event Reporting System (FAERS) and observational studies in common infections for tumor necrosis factor inhibitors (TNFi’s).

Methods: Using MedDRA® preferred terms, all infection cases in FAERS with each TNFi were retrieved using Evidex^TM. Observational studies reporting TNFi-related infections were identified from PubMed (OS-PM) and ClinicalTrials.gov (OS-CT). Infections with a reporting rate of ≥2% (based on percentage of total number of infections) from each data source were compiled. Fleiss’s kappa and Cohen’s kappa (κ) were calculated to determine agreement across all three sources and between each two sources.

Results: A total of 163,789 FAERS infection cases, 53 OS-PM studies and 52 OS-CT studies were identified. The Fleiss’ kappa that comparing all 3 data sources demonstrated lack of agreement. Significant moderate agreements were found between FAERS and OS-CT for etanercept and adalimumab, respectively (κ = 0.53, p = 0.02; κ = 0.56, p = 0.02), but no agreements (κ < 0) when comparing FAERS vs. OS-PM or OS-CT vs. OS-PM.

Conclusion: For common TNFi-related infections, passive (FAERS) and active (observational studies) pharmacovigilance results are similar between FAERS vs. OS-CT for etanercept and adalimumab but dissimilar across the 3 sources. Our findings suggest incorporating both active and passive pharmacovigilance methods in post-marketing drug safety assessment.

KEYWORDS:

• Active surveillance
• adverse events
• FAERS
• infections
• passive surveillance
• TNF inhibitors

Author contributions

All authors were involved in the conception and design; C Chen conducted the data synthesis and analysis, and all authors contributed to the interpretation of the data; C Chen drafted the initial paper and all authors revised it critically for intellectual content. All authors have provided the final approval of the version to be published, and all authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.