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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Contactos e Locais
Locais de estudo
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Beijing Municipality
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Beijing, Beijing Municipality, China, 100000
- China-Japan Friendship Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Método de amostragem
População do estudo
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
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
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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. |
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.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Disease progression
Prazo: From the start of tocilizumab treatment or second-line treatment to disease progression, the longest possible duration is until October 31, 2025.
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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%.
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From the start of tocilizumab treatment or second-line treatment to disease progression, the longest possible duration is until October 31, 2025.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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serum test of CK
Prazo: 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.
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The level of CK (U/L) in patients' serum
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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.
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Serum test of ferritin
Prazo: 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.
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The value of the ferritin (ng/ml) with serum test.
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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.
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Serum test of IL6
Prazo: 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.
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The value of the IL6 (pg/ml) with serum test.
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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.
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Serum test of LDH
Prazo: 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.
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The value of the LDH (U/L) with serum test.
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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.
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Serum test of CRP
Prazo: 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.
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The value of the CRP (mg/L) with serum test.
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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.
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PFS
Prazo: The time from the start of tocilizumab treatment or the first disease progression after second-line treatment, up to October 31, 2025.
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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;
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The time from the start of tocilizumab treatment or the first disease progression after second-line treatment, up to October 31, 2025.
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DLCO% predicted
Prazo: 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.
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The DLCO% predicted of thre patients
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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.
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FVC % predicted
Prazo: 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.
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FVC % predicted of the patient
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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.
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
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- 2026-KY-238
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