Interleukin 4-receptor-α blockade in localised scleroderma: a phase 2 proof-of-concept study
In brief
Dupilumab improved localized scleroderma and reduced inflammation in a six-month trial
In a randomized, placebo-controlled trial, six months of dupilumab improved localized scleroderma more than placebo and reduced local inflammation. The treatment also lowered disease-linked gene activity and partly suppressed genes involved in fibrosis, supporting a role for interleukin-4 and interleukin-13 signaling. Whether these benefits extend to other fibrosing diseases remains unknown.
- Journal
- Annals of the rheumatic diseases (Q1)
- Published
- 29 October 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Sabine A Eming, Alexander Kreuter, Matthias Hahn, Kamran Ghoreschi, Pia Moinzadeh, Nicolas Hunzelmann, et al.
- PMID
- 42957460
- DOI
- 10.1016/j.ard.2026.09.022
Why clinicians should know about it
- Picked for Immunology and Allergy (paper of the day, 31 October 2026): Randomized dupilumab trial targets immune-driven localized scleroderma
Abstract
OBJECTIVES: Fibrotic diseases are a major therapeutic challenge. In humans, fibrosing diseases are often associated with an interleukin (IL-) 4/TH2 signature. In preclinical mouse models, development of fibrosis critically depends on IL-4/signal transducer and activator of transcription 6 (STAT6). Yet, the role of IL-4/IL-13 in human fibrosing diseases remains unknown, and treatment development requires a deeper understanding of the role of IL-4/IL-13 in the pathogenesis. The local inflammation and the development of fibrosis in localised scleroderma (LS) are similar to those in systemic sclerosis and other fibrosing diseases. METHODS: In this article, we investigated the role of IL-4/IL-13 signalling in LS in a randomised, placebo-controlled clinical trial (ClinicalTrials.gov registration: NCT04200755). We studied the effect of 6 months of blocking IL-4-receptor α with dupilumab on disease progression, sclerosis-associated inflammation, and sclerosis-specific gene expression. RESULTS: Already this short-term intervention resulted in a significant clinical improvement over placebo, a significant attenuation of the local inflammation, a specific and significant reduction of the IL-4/IL-13-dependent gene signature, and a partial suppression of genes coding for fibrosis-inducing proteins. CONCLUSIONS: Thus, selective inhibition of IL-4/IL-13 prevents the progression of LS and is promising for therapeutic prevention of other fibrosing diseases.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.