Trends in immunosuppressant prescriptions among pregnant women in Japan during the period spanning the lifting of pregnancy contraindications: an administrative hospital database analysis

Abstract Background Cyclosporine, tacrolimus, and azathioprine were previously contraindicated during pregnancy in Japan. In July 2018, the Pharmaceuticals and Medical Devices Agency reassessed the teratogenic risks and lifted these contraindications. This study evaluated changes in prescription trends of these immunosuppressants among pregnant women. Methods We conducted a retrospective analysis of the administrative data for pregnant women treated at acute-care diagnosis procedure combination hospitals between August 1, 2015, and July 31, 2024. Cyclosporine, tacrolimus, and azathioprine were identified from their National Health Insurance Drug Codes. Prescriptions were counted only when accompanied by an ICD-10 code corresponding to an approved indication for the given drug. As a primary analysis, the annual prescription proportions were calculated as the number of pregnant women meeting this definition for each immunosuppressant divided by the total number of pregnant women identified in the corresponding year. A secondary analysis was conducted to examine the annual prescription proportions among pregnant women with diseases corresponding to immunosuppressant indications, using the same numerator as in the primary analysis; however, the denominator was restricted to pregnant women with the corresponding indication. Temporal trends were assessed using the Cochran–Armitage trend test. Results From 2015 to 2024, the prescription proportions among pregnant women increased from 0.016% to 0.035% for cyclosporine ( p < 0.01), from 0.023% to 0.130% for tacrolimus ( p < 0.001), and from 0.016% to 0.057% for azathioprine ( p < 0.001). Among pregnant women with diseases corresponding to immunosuppressant indications, no significant temporal trend was observed for cyclosporine (from 2.7% to 4.0%, p = 0.271), whereas significant increases were observed for tacrolimus (from 4.0% to 14.8%, p < 0.001) and azathioprine (from 2.7% to 6.5%, p < 0.001). The most common diagnoses recorded among pregnant women prescribed each immunosuppressant were nephrotic syndrome with cyclosporine, rheumatoid arthritis with tacrolimus, and systemic lupus erythematosus with azathioprine. Conclusions The proportion of tacrolimus and azathioprine prescriptions increased over time among pregnant women. These findings suggest that the regulatory revisions may have contributed to changes in real-world prescription practices.