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Certain non-cancer medications increase the risk of immune-related adverse events (irAE) in patients receiving immune-checkpoint inhibitors (ICI). This study identified specific drug combinations, like proton pump inhibitors and NSAIDs with ICI, that elevate irAE reporting.

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Area of Science:

  • Pharmacovigilance
  • Oncology
  • Immunology

Background:

  • Immune-checkpoint inhibitors (ICI) have transformed cancer therapy but can cause immune-related adverse events (irAE).
  • The influence of comedications on irAE occurrence is not well understood.
  • This study investigates the association between comedications and irAE in patients treated with ICI.

Purpose of the Study:

  • To identify comedications associated with an increased risk of irAE in patients receiving ICI.
  • To quantify the reporting odds ratio (ROR) for irAE linked to specific comedications.
  • To explore potential synergistic toxicity between certain comedications and ICI.

Main Methods:

  • A pharmacovigilance study using individual case safety reports (ICSRs) from the WHO Vigibase database (up to January 2024).
  • Analysis of suspect or interacting comedications, individually and by drug class (Anatomical Therapeutic Chemical classification level 4).
  • Calculation of the reporting odds ratio (ROR) to assess the association between comedications and irAE in ICI recipients.

Main Results:

  • Multiple comedications were linked to increased irAE reporting, including proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) with nephritis.
  • Statins were associated with myositis, ketoconazole with hepatitis, and dipeptidyl peptidase-4 inhibitors with autoimmune bullous disease.
  • Serious cutaneous adverse reactions were linked to PPIs, certain anti-infectives, allopurinol, and levetiracetam. Ibuprofen and influenza vaccines showed potential synergistic toxicity with ICI.

Conclusions:

  • This study identified several comedications associated with a higher risk of specific irAEs in patients treated with ICI.
  • Some identified drug combinations may exhibit synergistic toxicity, necessitating further investigation.
  • Findings highlight the importance of considering comedication use in managing irAEs in cancer patients receiving ICI therapy.