Tocilizumab for acute exacerbation of rheumatic disease-associated interstitial lung disease: a real-world comparative cohort study

Background Acute exacerbation of rheumatic disease-associated interstitial lung disease (AE-RD-ILD) is life-threatening and is commonly managed with high-dose corticosteroids; however, no standardised evidence-based regimen has been established, particularly regarding adjunctive immunosuppressive therapy. We evaluated the effectiveness and safety of tocilizumab, an interleukin-6 receptor inhibitor, in hospitalised patients with AE-RD-ILD. Methods In this single-centre ambispective observational cohort study conducted between January 2023 and December 2024, patients treated with tocilizumab (n=26) were compared with controls receiving corticosteroid-based conventional immunosuppression without tocilizumab (n=36). The primary outcome was investigator-defined objective composite clinical response (CR) at 24 weeks. Secondary outcomes included glucocorticoid exposure, oxygen discontinuation, radiological change, new acute exacerbation (AE) events, death or lung transplantation, and safety. Results The 24-week CR rate was higher with tocilizumab than in controls (80.8% [21/26] vs. 13.9% [5/36], p<0.001), with a risk ratio of 5.82 (95% CI 2.52-13.40) and an adjusted hazard ratio of 10.43 (95% CI 3.71-29.28); estimates were consistent in sensitivity analyses addressing competing risks, guarantee-time bias and additional confounders. Tocilizumab was associated with lower cumulative prednisone dose (3955 vs. 5005 mg, p=0.016), lower minimum maintenance dose (10.0 vs. 15.0 mg/day, p<0.001), more frequent oxygen discontinuation (76.9% vs. 30.6%, p<0.001), and greater CT-assessed reduction in ILD extent (20% vs. 15%, p=0.045). New AE events and death or lung transplantation were numerically less frequent but not statistically significant. At least one infection occurred in 23.1% of tocilizumab-treated patients and 38.9% of controls (p=0.272). During longer follow-up, seven controls subsequently switched to tocilizumab because of recurrent or progressive respiratory disease. Conclusions Tocilizumab was associated with higher short-term objective composite clinical response and improved respiratory and glucocorticoid-sparing outcomes in AE-RD-ILD. These findings support further evaluation of interleukin-6 receptor blockade in selected patients, while the non-randomised design and investigator-defined endpoint require cautious interpretation. Because the cohort was predominantly composed of patients with anti-synthetase-spectrum disease, the findings primarily apply to this phenotype and should not be extrapolated to RA-ILD, SSc-ILD or other RD-ILD subtypes without caution.