Antisynthetase Syndrome, Interstitial Lung Disease (ILD)
Conditions
Brief summary
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.
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.
Interventions
DRUGJAK 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.
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.
Sponsors
China-Japan Friendship Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-month survival rate | 12 months | Proportion of participants surviving at 12 months after randomization, with survival defined as the time from randomization to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annual decline rate of lung function (FVC% and DLCO%) | Change from baseline to 12 months | 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 in HRCT score | Change from baseline to 12 months | Change in high-resolution computed tomography (HRCT) score from baseline to 12 months, assessed using a standardized scoring system. |
| Rate of glucocorticoid tapering | Over 12 months | 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. |
| Proportion of patients achieving low disease activity (LDA) | At 6 months and 12 months | 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. |
Contacts
CONTACTQinghong Liu, MD
Outcome results
None listed