# Oral Corticosteroid Use and Its Associated Complications in Patients With Sarcoidosis: A Nationwide Claims Study From Japan

## TL;DR

This study finds that using oral corticosteroids for sarcoidosis in Japan increases the risk of several health complications, especially with higher doses.

## Contribution

The first nationwide study in Japan to show dose-dependent complications of oral corticosteroids in sarcoidosis patients using claims data.

## Key findings

- Higher cumulative OCS doses are linked to increased risks of pneumonia, hypertension, diabetes, and other complications.
- OCS users had significantly higher hazard ratios for pneumonia and steroid-related conditions like insomnia and hyperlipidemia.
- The study emphasizes the need for alternative treatments and personalized approaches to reduce corticosteroid-related risks.

## Abstract

Background: Corticosteroids are the first-line therapy for sarcoidosis due to their potent anti-inflammatory effects, providing symptomatic relief and slowing disease progression. In Japan, the association between cumulative corticosteroid exposure and the risk of steroid-related complications in patients with sarcoidosis remains unclear. In this study, we aimed to investigate real-world oral corticosteroid (OCS) dosing patterns and their association with adverse outcomes among patients with sarcoidosis using a nationwide claims database.

Methods: This retrospective cohort study used the Deidentified Scrubbed Claims Healthcare Database in Japan, covering approximately 20 million individuals between April 2014 and October 2023. Patients aged ≥18 years with a diagnosis of sarcoidosis were included. After applying eligibility criteria, patients who initiated OCS were matched 1:3 by index month with those who did not. Patients were followed for up to three years. Steroid-related complications were identified using diagnosis and treatment codes. The cumulative incidence of steroid-related complications was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to assess associations between three-year cumulative OCS dose and outcomes.

Results: Among 25,779 adults with sarcoidosis, 585 patients who initiated OCS were matched 1:3 with 1696 non-OCS patients, resulting in 2281 patients included in the analysis. Among OCS users, 401 (68.5%) initiated treatment within six months of diagnosis, with 220 (37.6%) receiving 30 mg/day as the most common initial dose. Compared with the non-OCS group, the hazard ratio (HR) for vertebral fracture was 1.43 (95% confidence interval (CI): 0.74-2.77) in the 1-4999 mg group and 2.13 (95% CI: 1.01-4.48) in the ≥5000 mg group. For pneumonia, HRs were 5.87 (95% CI: 4.43-7.79) and 13.47 (95% CI: 10.01-18.12), respectively. Cumulative OCS exposure in both the 1-4999 mg and ≥5000 mg groups was significantly associated with increased risks of herpes zoster, insomnia, hypertension, hyperlipidemia, and type 2 diabetes mellitus. Glaucoma was significantly associated only in the 1-4999 mg group, while cataract showed no significant association in either group.

Conclusion: Using a large-scale Japanese claims database, to the best of our knowledge, this study is the first to demonstrate that OCS use in sarcoidosis is associated with increased risks of dose-dependent complications. These findings emphasize the need for individualized treatment strategies and highlight the importance of expanding therapeutic options beyond corticosteroids.