Analysis conducted by Okayama University Hospital reveals that myocarditis risk increases with the concomitant use of thiazide diuretics

Immune checkpoint inhibitors are used in many patients with cancer; however, these can potentially cause serious side effects, including myocarditis, and the characteristics of patients who are likely to develop this condition are not well-understood.

A group consisting of Senior Assistant Professor Hirofumi Hamano and Professor Yoshito Zamami of the Department of Pharmacy at Okayama University Hospital, Pharmacist Satoru Mitsuboshi of Kaetsu Hospital (Niigata City), Assistant Professor Aya F. Ozaki and Professor Pranav Patel of the University of California, Irvine, Professor Keisuke Ishizawa of the Department of Pharmacy at Tokushima University Hospital, Associate Professor Toshihiro Koyama at the Graduate Schoole of Medicine, Dentistry and Pharmaceutical Sciences at Okayama University, Professor Yoshihiro Yamanishi of the Graduate School of Informatics at Nagoya University, and Director Yasunari Kanda of the Department of Pharmacology at the National Institute of Health Sciences (NIHS) collaborated on a research project to clarify the risk factors associated with myocarditis caused by immune checkpoint inhibitors by analyzing medical-information big data. They found that the concomitant use of immune checkpoint inhibitors and thiazide diuretics increases myocarditis occurrence risk. These results were published in the 12 June, 2023 issue of the International Journal of Cancer.

Determining patients who are prone to developing immune checkpoint inhibitor-induced myocarditis (a serious side effect) is important for the prevention of side effects and advancement of personalized medicine. However, sufficient clinical experience has not yet been accumulated in Japan because the side effect is extremely rare.

Therefore, the researchers consolidated worldwide information and conducted a detailed analysis of the occurrence of myocarditis caused by immune checkpoint inhibitors by utilizing the World Health Organization (WHO) adverse event reporting database 'VigiBase,' which contains tens of millions of side-effect reports.

First, they investigated the patients treated with immune checkpoint inhibitors and identified the concomitant drugs that frequently caused myocarditis. The result suggested that the concomitant use of immune checkpoint inhibitors and thiazide diuretics increased myocarditis risk. Further, they observed that the co-administration of immune checkpoint inhibitors with thiazide diuretics was likely to induce myocarditis even after ruling out the effects of other factors (such as age, sex, and concomitant use of other diuretics, among others).

This research utilizes medical information obtained from real-world big data and applies it to clinical settings where it is needed. Identifying drugs that may carry a risk of myocarditis will be beneficial for patients with various underlying diseases and therapeutic conditions, facilitating the selection of an optimal treatment approach for each patient undergoing drug therapy.

Hamano stated, "Through data science research using medical-information big data, I believe that I was able to contribute to the design of treatment strategies for the latest pharmacotherapy, which is currently attracting attention. This research is the result of collaborative efforts between domestic and foreign researchers. I will continue to build up evidence useful to the world and provide safe medical care to patients."

Journal Information
Publication: International Journal of Cancer
Title: Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics
DOI: 10.1002/ijc.34616