A Study on the Efficacy and Safety of JAK Inhibitors Versus Calcineurin Inhibitors as Initial Therapy for Interstitial Lung Disease Associated With Antisynthetase Syndrome

This is a single-center, randomized, open-label, prospective study. Eligible adults with interstitial lung disease associated with antisynthetase syndrome (ASS-ILD) who are treatment-naïve will be randomly assigned to receive either a JAK inhibitor (tofacitinib 5 mg twice daily, or baricitinib 4 mg once daily, or upadacitinib 15 mg once daily) or a calcineurin inhibitor (tacrolimus 0.075 mg/kg/day in two divided doses, or cyclosporine 2-5 mg/kg/day in two divided doses), both in combination with a standard glucocorticoid regimen. The primary endpoint is the 12-month survival rate. Secondary endpoints include changes in lung function, high-resolution CT (HRCT) scores, glucocorticoid dosage reduction, and the proportion of patients achieving low disease activity. Safety and laboratory parameters will be closely monitored throughout the 12-month treatment and follow-up period. Statistical analyses will compare the efficacy and safety profiles between the two treatment arms, and subgroup analyses will be performed to explore potential predictors of treatment response.

Inclusion criteria

• Age 18 to 75 years.
• Meet the 2017 EULAR/ACR diagnostic criteria for Anti-synthetase Syndrome (ASS).
• Presence of Interstitial Lung Disease (ILD) confirmed by High-Resolution Computed Tomography (HRCT).
• Active disease requiring initiation or intensification of immunosuppressive therapy, with no prior use of glucocorticoids, immunosuppressants, or biologics.
• Signed informed consent form.

Exclusion criteria

• Diagnosis of Rapidly Progressive ILD (RP-ILD), defined as worsening dyspnea within 1 month and PaO2/FiO2 ratio < 250 mmHg.
• Active uncontrolled severe infection, malignancy, or major organ failure.
• Pregnancy or lactation.
• Contraindications to the study drugs.
• Concurrent use of other immunosuppressants or biologics.