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.

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.

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