Disproportionality analysis of bullous pemphigoid adverse events with PD-1 inhibitors in the FDA adverse event reporting system

ABSTRACT

Objectives: Bullous pemphigoid, an autoimmune dermatological disease, may be associated with the use of a relatively new anti-cancer drug class, PD-1 inhibitors, which includes pembrolizumab and nivolumab. This paper analyzes the signals between PD-1 inhibitors and bullous pemphigoid based upon the reported real-world data.

Methods: A pharmacovigilance analysis was performed on the publicly available Adverse Event Reporting System database of Food and Drug Administration. Disproportionality ratios were used to examine a signal between PD-1 inhibitors and bullous pemphigoid. A heat map was generated to depict the signal between PD −1 inhibitor use and skin toxicity adverse events.

Results: The analysis indicated that there is a significant signal (PRR = 13.82 [95% CI: 9.99–19.11], Chi-squared with Yates’ correction = 420.48) between pembrolizumab use and bullous pemphigoid and that there is a significant signal (PRR = 13.19 [95% CI: 10.57–16.46], Chi-squared with Yates’ correction = 869.71) between nivolumab use and bullous pemphigoid. The signals remained statistically significant after stratifying for sex and age for both pembrolizumab and nivolumab. The signal is supported by 35 case reports in which there was evidence of PD-1 inhibitor use and a pemphigoid adverse event.

Conclusion: When prescribing PD-1 inhibitors, physicians should monitor closely for symptoms of bullous pemphigoid.

KEYWORDS:

• Bullous pemphigoid
• PD-1 inhibitor
• pharmacovigilance
• drug safety
• pembrolizumab
• nivolumab

Author contributions

P Aggarwal was involved in the conception and design, and analysis and interpretation of the data; the drafting of the paper and revising it critically for intellectual content, and the final approval of the version to be published.

Declaration of interest

The author has 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.