TOPLINE

Patients with systemic sclerosis (SSc) from an international registry cohort who were treated with a JAK inhibitor had a high discontinuation rate, dealt with adverse events that included infections and malignancies, and appeared to have therapeutic outcomes similar to those seen with standard immunosuppressives.

METHODOLOGY

• Researchers conducted a longitudinal retrospective analysis using data from the European Scleroderma Trials and Research group database to evaluate the safety profile and effectiveness of JAK inhibitors in patients with SSc.
• They included 36 patients who received JAK inhibitors (baricitinib, tofacitinib, or upadacitinib; median age, 57 years; 81% female individuals) and were followed up between November 2017 and December 2024, with a median duration of drug exposure of 37 months.
• Patients who received JAK inhibitors were compared with those who received mycophenolate mofetil, rituximab, or methotrexate, using propensity score matching, resulting in 180 matched patients in each comparator group.
• The primary outcomes assessed were safety, comprising the incidence of adverse events (including serious and nonsevere infections, new malignancies, venous thromboembolism, and major adverse cardiovascular events) and drug survival (defined as the time to permanent discontinuation of treatment).
• Secondary outcomes to determine effectiveness included changes in forced vital capacity (FVC) percent predicted, modified Rodnan Skin Score (mRSS) in patients with diffuse cutaneous SSc, swollen joint count, all assessed at 12 and 24 months; digital ulcer recurrence or calcinosis were also assessed.

TAKEAWAY

• Over follow-up, 23 adverse events occurred (23.3 events per 100 patient-years): 12 new infections, seven laboratory abnormalities, three malignancies, and one fatal event (sepsis with multiorgan failure).
• Overall, 33.3% of patients permanently discontinued JAK inhibitor therapy, mainly due to treatment failure; the estimated drug retention rates were 81%, 64%, and 43% at 12, 24, and 36 months, respectively.
• At 12 and 24 months, the mean change in FVC among patients who received JAK inhibitors vs mycophenolate mofetil, rituximab, or methotrexate did not differ significantly. Among patients with diffuse cutaneous SSc, the change in mRSS was not significantly different between those who received JAK inhibitors and comparator treatments.
• During follow-up, at least one digital ulcer was noted in 30.5% of patients who received JAK inhibitors, and no difference was seen in the occurrence or recurrence of digital ulcers between the JAK inhibitor and comparator therapy groups. Calcinosis was observed in 27.7% of patients at baseline and persisted throughout follow-up.

IN PRACTICE

“[The study] findings are encouraging, although safety concerns are important practical considerations, in particular cancer and infection risk. There were tentative signals of effectiveness for fibrotic lung and skin manifestations, as well as musculocutaneous and vascular complications. Our findings may point to a potential signal of benefit in patients within the diffuse subset and with features of an inflammatory phenotype; however, these observations are exploratory and hypothesis-generating,” the authors wrote.

SOURCE

This study was led by Stefano Di Donato, MD, University of Leeds in Leeds, England. It was published online on June 15, 2026, in Arthritis Care & Research. 

LIMITATIONS

The sample size of patients treated with JAK inhibitors was small, limiting statistical power. The small number of events precluded multivariable analyses. Safety data were available only for patients treated with JAK inhibitors, and comparisons with other therapies could not be performed.

DISCLOSURES

This study did not receive any specific funding. Several authors reported receiving speaker fees, research grants, consulting fees, payments or honoraria for lectures, and having other ties with multiple pharmaceutical companies and other organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.