Tocilizumab in Refractory ASS-ILD

Tocilizumab for Refractory Anti-Synthetase Syndrome-Associated Interstitial Lung Disease: A Real-World Retrospective Cohort Study

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.

Study Overview

• Status: Completed
• Conditions: Antisynthetase Syndrome; Tocilizumab
• Intervention / Treatment: Drug: Tociliuzumab

• Study Type: Observational
• Enrollment (Actual): 111

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • China-Japan Friendship Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Refractory anti-synthetase syndrome-associated interstitial lung disease; 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; and (4) missing key outcome data.

Drug: Tociliuzumab; Tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, is approved for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and giant cell arteritis. In patients with rheumatoid arthritis-associated ILD, tocilizumab has been shown to reduce KL-6 levels, a biomarker of alveolar epithelial injury. However, evidence for tocilizumab in ASyS-ILD is limited to isolated case reports, and no systematic evaluation of its efficacy and safety in this specific population has been published.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease progression	Disease progression is classified data, which included the number of patients with symptoms progression（Symptom progression was defined as worsening of dyspnea, cough or rash requiring escalation of therapy or hospitalization） or with the worsening of pattern demonstrated on CT scans (defined as an increase in the extent of reticulation, traction bronchiectasis, or honeycombing on follow-up HRCT ) or the number of the patients with FVC% decline >10% or with DLCO% decline >15%.	From the start of tocilizumab treatment or second-line treatment to disease progression, the longest possible duration is until October 31, 2025.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum test of CK	The level of CK (U/L) in patients' serum	From the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.
Serum test of ferritin	The value of the ferritin (ng/ml) with serum test.	From the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.
Serum test of IL6	The value of the IL6 (pg/ml) with serum test.	From the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.
Serum test of LDH	The value of the LDH (U/L) with serum test.	From the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.
Serum test of CRP	The value of the CRP (mg/L) with serum test.	From the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.
PFS	progression-free survival (PFS), defined as the time (months) from second-line treatment initiation to symptom progression, CT progression, lung function decline, or death from any cause, whichever occurred first;	The time from the start of tocilizumab treatment or the first disease progression after second-line treatment, up to October 31, 2025.
DLCO% predicted	The DLCO% predicted of thre patients	Before the treatment with tocilizumab or the second-line treatment, and from the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.
FVC % predicted	FVC % predicted of the patient	Before the treatment with tocilizumab or the second-line treatment, and from the start of tocilizumab treatment or the start of second-line treatment, within 3 months (within 2 weeks before or after), up to October 31, 2025.

Collaborators and Investigators

• Sponsor: Hu Yinan

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): October 31, 2025
• Study Completion (Actual): October 31, 2025

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 17, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: tocilizumab; treat; ASyS-ILD
• Additional Relevant MeSH Terms: Antisynthetase syndrome; tocilizumab
• Other Study ID Numbers: 2026-KY-238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The study methods will be made publicly available after article publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No