Refractory anti-synthetase syndrome-associated interstitial lung disease (ASyS-ILD) lacks targeted therapy. Interleukin-6 drives both inflammation and fibrosis. We evaluated the real-world efficacy and safety of tocilizumab, an IL-6 receptor antagonist.

This single-center retrospective cohort study included patients with refractory ASyS-ILD treated between January 2020 and July 2025. Tocilizumab recipients were compared with those receiving standard of care (SOC) immunosuppressants. Overlap weighting based on propensity scores was used to balance 11 baseline variables. The primary outcome was improvement in symptoms and HRCT findings at ≥3 months. Secondary outcomes included changes in biomarkers and pulmonary function, progression-free survival (PFS), and adverse events. Cox regression identified independent predictors of symptom progression. Generalized additive models (GAM) explored nonlinear relationships, and XGBoost-SHAP machine learning assessed variable importance.

Inclusion Criteria:

• age ≥18 years;
• fulfillment of the 2017 EULAR/ACR classification criteria for ASyS;
• HRCT-confirmed ILD;
• refractory disease, defined as active disease despite prior treatment with glucocorticoids and at least one first-line immunosuppressant (including methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, cyclophosphamide, baricitinib, or upadacitinib);
• availability of baseline and follow-up clinical data at ≥3 months.

Exclusion Criteria:

• pregnancy or lactation;
• pre-existing psychiatric disorders that would preclude study participation;
• prior lung transplantation;
• missing key outcome data;
• Patients with Anti-MDA5 dermatomyositis.

We reviewed electronic medical records of all adult patients diagnosed with ASyS-ILD at our institution between January 1, 2020, and July 30, 2025.

Inclusion criteria were: (1) age ≥18 years; (2) fulfillment of the 2017 EULAR/ACR classification criteria for ASyS; (3) HRCT-confirmed ILD; (4) refractory disease, defined as active disease despite prior treatment with glucocorticoids and at least one first-line immunosuppressant (including methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, cyclophosphamide, baricitinib, or upadacitinib); and (5) availability of baseline and follow-up clinical data at ≥3 months.

Exclusion criteria were: (1) pregnancy or lactation; (2) pre-existing psychiatric disorders that would preclude study participation; (3) prior lung transplantation; (4) missing key outcome data; (5) Patients with Anti-MDA5 dermatomyositis.

Patients who received tocilizumab (8 mg/kg intravenously every 4 weeks) were assigned to the tocilizumab group (N=41). Patients who

The study methods will be made publicly available after article publication.