A narrative review on immune checkpoint inhibitor drug interactions with statins, proton pump inhibitors and corticosteroids

Abstract

Abstract Background Immune checkpoint inhibitors (ICI) are increasingly and highly used in aging cancer patients with polypharmacy. The common comedications, such as statins, proton pump inhibitors (PPIs), and corticosteroids, have the potential to interact with ICIs and alter their effectiveness and toxicity, although a synthesis of this evidence is not offered in detail. Objective To conduct a narrative review and summarize available preclinical and clinical evidence on the impact that concomitant statin, PPI, and systemic corticosteroids had on the (overall/progression-free survival) and safety (immune-related adverse events) of ICI therapy. Methodology We conducted a narrative review on the base of systematic search in PubMed/MEDLINE, Embase, and Web of Science (January 2020–April 2026). The subject of the thematic synthesis of literature on interactions between ICIs (anti-PD-1/PD-L1, anti-CTLA-4) and the three classes of drugs. All quantitative estimates are obtained by means of the published meta-analyses and cohort analyses, no additional pool analysis was conducted. Key findings According to published meta-analyses reports, statin use is associated with improved ICI effectiveness in some studies, because of their impact on antitumor immunity through mevalonate pathway inhibition (pooled HR for OS: 0.8; 95% CI: 0.71–0.92). It has been repeatedly shown in multiple observational studies that PPIs consistently reduce efficacy of ICIs because of their dose-dependent gut microbiome dysbiosis effect which becomes especially harmful when patients exceed high usage before ICI treatment (pooled HR ~ 1.18). The relationship of corticosteroids and ICI outcome seems situation-specific based on observational data: baseline use (≥ 10 mg prednisone equivalent), by contrast, has been indicated to be negatively correlated with long-term outcomes in retrospective cohorts (HR ~ 1.54), whereas therapeutic administration for immune-related side effects does not seem to reduce long-term survival advantage in reported studies. Conclusion Observational studies indicated that concomitant medications have significant effect on ICI outcomes due to pharmacodynamics interaction. Reducing the prescription of needless PPIs during ICI therapy, thorough rationale for baseline corticosteroids and statin continuation (if clinically required) may be justified, although prospective studies should pay more attention to validate relationships. Although preclinical research and observational data provide the majority of the evidence, concurrent drugs may also impact the effectiveness of ICIs through pharmacodynamic processes.