Antibiotics reduce efficacy of immune checkpoint inhibitors

Use of antibiotics during immune checkpoint blockade (ICB) has a significantly negative impact on the efficacy of immunotherapy, reveals a study. The greatest negative impact occurs when using antibiotics in the first 6 weeks after initiating ICB.

In this single-institution retrospective study, the authors evaluated the impact of antibiotics on the outcomes of patients with advanced or metastatic malignancy who were treated with ICB. They also assessed the use of antibiotics among patients receiving ICB during a 12-week period before and after ICB initiation. Response to ICB was the primary outcome. Histologic changes in the tumour microenvironment following antibiotic use were also examined.

A total of 414 patients who received ICB were identified between 1 January 2011 and 31 December 2018, of whom 207 (50 percent) received antibiotics within 12 weeks before and after ICB initiation.

Univariate analysis revealed the association of antibiotic use following ICB initiation with a significantly reduced response (odds ratio [OR], 0.33, 95 percent confidence interval [CI], 0.2–0.52; p<0.001). Use of antibiotics prior to ICB initiation showed no significant impact on response to immunotherapy (OR, 0.87, 95 percent CI, 0.55–1.34; p=0.52).

The negative impact of antibiotics reached its zenith in the first 6 weeks after initiating ICB and was independently correlated with markedly decreased likelihood of response to immunotherapy in multivariable analysis (OR, 0.48, 95 percent CI, 0.29–0.8; p=0.01).

“Antibiotic use can result in reduced efficacy of ICB, presumably because of dysbiosis of the intestinal microbiome,” the authors said.