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.

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.

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