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Upadacitinib Outperforms Mycophenolate in SSc-ILD Treatment
BARCELONA, Spain — The JAK inhibitor upadacitinib can effectively treat systemic sclerosis-associated interstitial lung disease (SSc-ILD), according to results from a new clinical trial.
Patients treated with upadacitinib had reduced rates of decline in forced vital capacity (FVC) at 24 weeks of treatment compared to those treated with mycophenolate mofetil. After 1 year, the difference in the annual rate of decline between the two groups was 20.9 mL/y, favoring upadacitinib ( P = .05).
'We can conclude that upadacitinib was an effective treatment for interstitial lung disease,' said first author Manal Hassanien, MD, PhD, of Assiut University in Asyut, Egypt. She presented the clinical findings at European Alliance of Associations for Rheumatology (EULAR) 2025 Annual Meeting.
'It has a beneficial effect in reducing the rate of decline in FVC in patients with SSc-ILD, [with] some beneficial response in the skin of the diffuse type of systemic sclerosis, and an acceptable safety profile.'
Upadacitinib is currently approved by the FDA for the treatment of rheumatoid arthritis, adult and juvenile psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis. Currently, nintedanib and tocilizumab are the only FDA-approved treatments for SSc-ILD.
Commenting on the study for Medscape Medical News , Iulia Szabo, MD, PhD, a rheumatologist at 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania, said the results were 'really promising.'
Previous systematic reviews of the literature have also found encouraging evidence using other JAK inhibitors, such as tofacitinib, in SSc-ILD treatment, although the data were mostly in vitro or experimental, Szabo said. She moderated the session where the abstract was presented.
'In a field where we have so little options at our disposal, this [study] is very interesting,' she said.
Study Details
In the double-blinded, randomized study, researchers enrolled 57 patients with SSc with disease onset of more than 3 years. Of these patients, 57% had the diffuse cutaneous type of SSc. All patients had an FVC < 75% of the predicted normal value, a diffusing capacity of the lungs for carbon monoxide (DLCO) < 80% of the predicted normal value, and at least 10% fibrosis scarring in a high-resolution CT scan. Patients were aged on average about 33 years, and 80% were women.
Patients were randomly assigned in a 1:1 ratio to receive a daily dose of 15 mg upadacitinib or 2000 mg mycophenolate. Researchers assessed FVC decline at 12, 24, and 52 weeks, as well as DLCO and changes in the modified Rodnan skin score (mRSS).
At 52 weeks, 20.6% of the upadacitinib group and 37.5% of the mycophenolate group had ≥ 5% absolute decline from baseline in FVC. A 10% drop in FVC from baseline at 1 year was also more common in patients taking mycophenolate (17.9%) than in those taking upadacitinib (6.8%).
The change in DLCO (as a percentage of the predicted value) at 52 weeks was -62.7 mL in the upadacitinib group and -93.3 mL in the mycophenolate group. The change from baseline in mRSS in patients with the diffuse type of SSc was numerically different between the two groups after 1 year, but this difference was not statistically significant. No significant adverse events were detected in either group.
Because the age of the participants in this study trended younger, there may be a higher risk for these events as patients age, Szabo noted.
'The problem we might have will be with older patients because we know all the adverse effects that JAK inhibitors have, and probably we should be a bit more cautious,' she said.
