OP0336 COMMONLY USED DRUGS IN RHEUMATOLOGY MAY ALTER ANTI-TUMORAL RESPONSE TO IMMUNE CHECKPOINT INHIBITORS
Authors: Marie Kostine, Eleonora Mauric, Thomas Barnetche, Léa Rouxel, Caroline Dutriaux, Léa Dousset, Sorilla Prey, Marie Beylot-Barry, Julien Seneschal, Rémi Veillon, Charlotte Vergnenegre, Amaury Daste, Charlotte Domblides, Baptiste Sionneau, Marine Gross-Goupil, Alain Ravaud, Edouard Forcade, Bernard Bannwarth, Marie-Elise Truchetet, Christophe Richez, Nadia Mehsen-Cetre, Thierry Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Immune checkpoint inhibitors (ICIs) are revolutionizing the treatment of some advanced cancers. Gut microbiota has emerged as an important component of anti-tumoral response and can also be related to the occurrence of immune-related adverse events (irAEs). It has recently been shown that antibiotic treatment given at the initiation of ICI therapy had a dramatic impact on microbiota that compromised the anti-tumoral effect of ICIs (1). <h3>Objectives</h3> To evaluate whether co-medications known to have a potential impact on gut microbiota may alter ICI efficacy and/or irAE occurrence when given at ICI onset. <h3>Methods</h3> This was a retrospective cohort study including all cancer patients who received ICIs at our institution from May 2015 to September 2017. Co-medications given to the patients within one month before or one month after the first administration of ICI were extracted from medical records on the basis of a predefined list of medications known to impact gut microbiota. The tumour response, occurrence of irAEs and patient outcomes were assessed on a regular basis. Overall survival (OS) has been considered from the start of ICI therapy. <h3>Results</h3> 635 patients (70% male, mean age 64.5 years) were included, of whom 293 had melanoma, 150 had advanced non-small cell lung cancer and 83 had renal carcinoma. A previous autoimmune disorder was present in 8% of patients, mainly rheumatic and endocrine diseases. Psychotropic drugs (41.1%), proton pump inhibitors (PPIs) (37.3%), angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARBs) (32%), glucocorticoids (GC) (24.2%), antibiotics (21.4%), statins (20.8%) and morphine (20.6%) were the most co-prescribed medications. Baseline GC use, when ≥ 10mg of prednisone equivalent, was associated with a significant decrease in OS (median 4.5 months versus 24.3 months; p&lt;0.0001) and a less frequent tumour response (55% versus 73%; p=0.0001). When given after ICI onset for the management of irAEs, GC did not influence ICI efficacy (<b>Figure A</b>). Baseline PPIs use also altered both OS (median 10.9 versus 24.3 months; p&lt;0.0001) and tumour response (62% versus 71%; p=0.02) (<b>Figure B</b>). We confirmed the detrimental impact of antibiotics when given at ICI onset, and also found worse outcomes for patients receiving baseline psychotropic drugs (median OS 9.3 versus 19.4 months; p=0.0001). No significant difference was observed with baseline use of NSAIDs, aspirin, statins and ARBs/ACE. Furthermore, co-medication with antibiotics, GC, PPIs, morphine, NSAIDs, aspirin and psychotropic drugs was associated with decreased occurrence of irAEs. <h3>Conclusion</h3> As many of these treatments are used by rheumatologists, one should be aware of their potential detrimental effect when used at ICI initiation, that sometimes could have been avoided. <h3>Reference</h3> [1] Routy B et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan 5;359(6371):91-97. <h3>Disclosure of Interests</h3> None declared