Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.
PURPOSE
Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice.


MATERIALS AND METHODS
A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression.


RESULTS
We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001).


CONCLUSION
Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.
['Pérez-Ruiz|E|E|http://orcid.org/0000-0001-7204-0800', 'Jiménez-Castro|J|J|', 'Berciano-Guerrero|M-A|MA|', 'Valdivia|J|J|', 'Estalella-Mendoza|S|S|', 'Toscano|F|F|', 'Rodriguez de la Borbolla Artacho|M|M|', 'Garrido-Siles|M|M|', 'Martínez-Bautista|M J|MJ|', 'Villatoro Roldan|R|R|', 'Rivas-Ruiz|F|F|', 'Nogales-Fernández|E|E|', 'Morales|C|C|', 'Pérez-Valderrama|B|B|', 'De la Cruz-Merino|L|L|', 'Rueda|A|A|']
D000305:Adrenal Cortex Hormones D000328:Adult D000368:Aged D000369:Aged, 80 and over D000863:Antacids D014151:Anti-Anxiety Agents D002289:Carcinoma, Non-Small-Cell Lung D064806:Dysbiosis D005260:Female D006801:Humans D000082082:Immune Checkpoint Inhibitors D008175:Lung Neoplasms D008297:Male D008545:Melanoma D008875:Middle Aged D012189:Retrospective Studies
Immune checkpoints inhibitors Intestinal dysbiosis Clinical response