# Azathioprine as maintenance therapy for IgG4-related diseases: a retrospective case series and case-based review of the literature

## TL;DR

Azathioprine is a safe and effective long-term treatment for IgG4-related disease, helping many patients stay in remission and reduce steroid use.

## Contribution

This study provides real-world evidence supporting azathioprine as a maintenance therapy for IgG4-related disease.

## Key findings

- Seven out of ten patients remained in remission during azathioprine therapy.
- Three patients experienced relapses, suggesting azathioprine may not be sufficient for all cases.
- Adverse events were manageable, with infections and blood-related issues being the most common.

## Abstract

IgG4-related disease (IgG4-RD) is a rare fibro-inflammatory disorder characterized by progressive fibrosis involving multiple organs and tissues. Clinical manifestations are highly variable, reflecting the organs affected. Oral glucocorticoids (GC) are established as first-line therapy; however, relapse occurs in 15–60% of patients. To reduce relapse risk and GC-related adverse effects, GC-sparing strategies using disease-modifying antirheumatic drugs (DMARDs) may be considered. This study aims to evaluate the efficacy and safety of azathioprine in the management of IgG4-RD and provides an overview of the current literature. This retrospective case series assesses disease activity under azathioprine therapy in patients with IgG4-RD treated at the Medical University of Graz between 2006 and 2024. Patients with a confirmed IgG4-RD diagnosis according to the 2019 ACR/EULAR criteria who received azathioprine following initial GC therapy were included. Ten male patients (mean age at disease onset: 59.4 years) with a mean follow-up of 75.2 months were analyzed. All patients fulfilled the 2019 ACR/EULAR classification criteria. Indications for initiating azathioprine included disease relapse on GC (n = 3), GC-related adverse effects (n = 3), and the intention to reduce GC exposure (n = 7). During azathioprine therapy, three patients (30%) experienced a total of five relapses. Seven patients receiving azathioprine remained in remission throughout the observation period. Adverse events included infections (n = 2), hematologic abnormalities (n = 4), and elevated liver enzymes (n = 1). At last follow-up, five patients (50%) remained on azathioprine, two (20%) had switched to rituximab, one of whom was in remission and off therapy, and three patients (30%) were no longer receiving immunosuppressive treatment (two due to hematologic abnormalities, one by patient request), with no further therapy initiated. Azathioprine represents an appropriate maintenance therapy for IgG4-RD. In cases with relapse under azathioprine, alternative DMARDs, such as CD19- or CD20-targeted therapies, may be more effective.

The online version contains supplementary material available at 10.1007/s00296-026-06083-7.