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

This study is a prospective investigation comparing the efficacy and safety of Janus kinase inhibitors versus calcineurin inhibitors as initial therapy for interstitial lung disease associated with antisynthetase syndrome. The goal is to determine which treatment is more effective at improving lung function and preventing disease progression, while comparing their safety profiles. The findings will help provide clearer treatment guidance for doctors and patients.

Study Overview

• Status: Recruiting
• Conditions: Interstitial Lung Disease (ILD); Antisynthetase Syndrome
• Intervention / Treatment: Drug: JAK Inhibitor; Drug: Calcineurin Inhibitors (CNI)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qinghong Liu, MD; Phone Number: +86 15774917676; Email: 166618530@qq.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • Recruiting
      • China-Japan Friendship Hospital
      • Contact: Qinghong Liu; Phone Number: 15774917676; Email: 166618530@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JAK inhibitor group; Participants in this arm will receive one of the JAK inhibitors (tofacitinib 5 mg twice daily, or baricitinib 4 mg once daily, or upadacitinib 15 mg once daily) in combination with a standard glucocorticoid regimen (methylprednisolone 0.5g IV for 3 days, followed by oral prednisone 0.8-1.0 mg/kg/day tapered to 7.5 mg/day over 12 months). Treatment duration is 12 months.	Drug: JAK Inhibitor; Oral JAK inhibitors (tofacitinib 5 mg twice daily, or baricitinib 4 mg once daily, or upadacitinib 15 mg once daily) administered in combination with standard glucocorticoid therapy for 12 months.
Experimental: Calcineurin inhibitor group; Participants in this arm will receive either tacrolimus (0.075 mg/kg/day in two divided doses) or cyclosporine (2-5 mg/kg/day in two divided doses) in combination with the same standard glucocorticoid regimen as the experimental group. Treatment duration is 12 months.	Drug: Calcineurin Inhibitors (CNI); Oral calcineurin inhibitors (tacrolimus 0.075 mg/kg/day in two divided doses, or cyclosporine 2-5 mg/kg/day in two divided doses) administered in combination with standard glucocorticoid therapy for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month survival rate	Proportion of participants surviving at 12 months after randomization, with survival defined as the time from randomization to death from any cause.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual decline rate of lung function (FVC% and DLCO%)	The annual rate of decline in forced vital capacity (FVC% predicted) and diffusing capacity for carbon monoxide (DLCO% predicted), calculated as the change from baseline to 12 months.	Change from baseline to 12 months
Change in HRCT score	Change in high-resolution computed tomography (HRCT) score from baseline to 12 months, assessed using a standardized scoring system.	Change from baseline to 12 months
Rate of glucocorticoid tapering	The rate of glucocorticoid dose reduction over 12 months, calculated as the time to achieve prednisone ≤7.5 mg/day or the cumulative glucocorticoid dose.	Over 12 months
Proportion of patients achieving low disease activity (LDA)	Proportion of participants achieving low disease activity (LDA) at 6 and 12 months, defined as meeting all of the following criteria: no active arthritis without regular NSAID use; no active myositis with serum creatine kinase ≤ upper limit of normal; stable ILD with no decline in pulmonary function (FVC decline <5% and DLCO decline <10% in the past 6 months); no fever or other systemic manifestations with ESR <20 mm/h; stable glucocorticoid dose ≤7.5 mg/day (prednisone equivalent) for at least 3 months.	At 6 months and 12 months

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 18, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 6, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Antisynthetase syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Pharmacologic Actions; Chemical Actions and Uses; Janus Kinase Inhibitors; Calcineurin Inhibitors
• Other Study ID Numbers: JAKCNIASSILD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No