PO73 - Targeting the JAK-STAT pathway in Progressive Fibrotic Pulmonary Sarcoidosis: Functional and Physiologic Improvement with Tofacitinib in a 20-Patient Case Series
Arda Kiani (Iran)1; Atefeh Abedini (Iran)2; Pegah Soltani (Iran)2; Akram Ghanavati (Iran)2; Kimia Taghavi (Turkey)2 3;
1 - Tehran Lung Research and Development Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2 - Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3 - Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Kultur University, Istanbul, Turkey;
Keywords: Sarcoidosis;; fibrotic lung disease;; tofacitinib;;
Select the theme: Challenges in Sarcoidosis Diagnosis and Staging
Type: Original Papers
Presentation: Poster Presentation

Introduction: Background

Progressive fibrotic pulmonary Sarcoidosis is associated with significant morbidity and limited response to conventional immunosuppressive therapies. Increasing evidence implicates activation of the JAK-STAT pathway in the pathogenesis of granulomatous inflammation and fibrotic progression, providing a rationale for targeted therapeutic intervention with Tofacitinib.


Objectives: To evaluate the clinical efficacy and safety of tofacitinib, a JAK inhibitor, in patients with progressive fibrotic pulmonary sarcoidosis refractory to conventional immunosuppressive therapy, and to assess its impact on pulmonary function, exercise capacity, oxygenation, and radiologic progression.

Materials and Methods: Methods

We conducted a retrospective case series of 20 patients with progressive fibrotic pulmonary sarcoidosis refractory to corticosteroids and at least one steroid-sparing immunosuppressive agent. The cohort included 15 males and 5 females, with a mean age of 54 years. Patients received tofacitinib and were followed for 6 months. Primary and secondary outcomes included changes in forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), 6-minute walk test (6MWT), oxygen saturation, symptom burden, and radiologic progression on high-resolution computed tomography (HRCT).


Results: Results

After 6 months of treatment, most patients demonstrated clinical improvement or stabilization of respiratory symptoms. Mean FVC increased by approximately 10% from baseline. DLCO improved by 10%. Functional capacity significantly improved, with a 15% increase in 6-minute walk distance. Oxygen saturation increased by approximately 5% during follow-up. Radiologic assessment suggested attenuation of fibrotic progression in several patients. Tofacitinib was generally well tolerated. One patient developed herpes zoster, which resolved without complications. No other serious adverse events were observed.


Conclusions: Conclusion

In this case series, tofacitinib was associated with clinically meaningful improvements in lung function, gas exchange, exercise capacity, and oxygenation over 6 months in patients with progressive fibrotic pulmonary sarcoidosis refractory to standard therapy. These findings support further prospective controlled studies to evaluate JAK inhibition as a novel therapeutic strategy in fibrotic sarcoidosis.


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