Tocilizumab in refractory anti-synthetase syndrome-associated interstitial lung disease:a phenotype-stratified cohort study

Anti-synthetase syndrome-associated ILD (ASyS-ILD) spans a spectrum from active inflammation to established fibrosis; IL-6 pathway involvement supports a rationale for tocilizumab, yet phenotype-specific efficacy data are lacking. Thirty-two patients with refractory ASyS-ILD received intravenous tocilizumab (8 mg/kg every 4 weeks) for ≥ 3 months. Patients were stratified into three phenotypes: glucocorticoid-dependent ( n = 8, unable to taper prednisone below 15 mg/day without relapse), glucocorticoid-resistant ( n = 18, failure to achieve remission despite ≥ 3 months of induction therapy), and progressive pulmonary fibrosis (PPF, n = 6, fulfilling ≥ 2 symptom/physiological/radiological progression criteria within 12 months on stable immunosuppression without active inflammation). Changes in lung function, high-resolution computed tomography (HRCT) scores and glucocorticoid dosage were analyzed using generalised estimating equations and paired tests. Improvements in forced vital capacity (FVC)% predicted, diffusing capacity for carbon monoxide (DLCO)% predicted, and HRCT scores were observed at 3 months and sustained at 6 months. Among the glucocorticoid-dependent group, 7/8 patients (87.5%) tapered prednisone to ≤ 10 mg/day. Sixteen of 18 glucocorticoid-resistant patients (88.9%) achieved treatment response. In the PPF subgroup, aggregate lung function did not improve from baseline; however, 5/6 patients (83.3%) showed FVC trajectories shifting from decline toward stabilisation or improvement (mean slope difference, + 0.81% predicted/month; 95% CI, -0.11 to 1.73; p = .073). No severe adverse events or treatment-related deaths occurred. In this retrospective study, tocilizumab was associated with glucocorticoid tapering and reduced disease activity in glucocorticoid-dependent and -resistant patients. In the PPF subgroup, lung function did not change significantly on between-timepoint analysis, and a slope-based analysis suggested possible attenuation of decline that did not reach statistical significance. These hypothesis-generating findings provide a phenotype-based rationale for prospective controlled trials.