Tocilizumab for the treatment of acute exacerbation of idiopathic pulmonary fibrosis: A matched case-control retrospective study.

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a lethal condition with mortality exceeding 50% at 3 months, driven by hyperinflammation. Elevated interleukin-6 (IL-6) is associated with poor outcomes. Tocilizumab (TCZ), an IL-6 receptor antagonist, may modulate this harmful inflammation.ObjectivesTo evaluate the efficacy and safety of tocilizumab combined with corticosteroids in AE-IPF.DesignRetrospective, propensity score-matched, case-control study.MethodsThirty-nine AE-IPF patients from a registry (NCT03666234) were included. Thirteen received tocilizumab (8 mg/kg) plus methylprednisolone, matched 1:2 to 26 receiving conventional therapy. The primary outcome was 3-month all-cause mortality or lung transplantation. Secondary outcomes included changes in ground-glass opacity (GGO) scores and inflammatory biomarkers.ResultsBaseline characteristics were balanced. A GGO score ≥18 predicted higher mortality (HR 5.01, 95% CI 1.47-17.14; p=0.01). In univariable analysis, TCZ was associated with a lower but non-significant risk of the 90-day composite endpoint compared with conventional therapy (unadjusted HR 0.39, 95% CI 0.13-1.18; p=0.095). In an exploratory multivariable Cox model adjusting for baseline GGO score and inflammatory markers, TCZ was associated with a significant risk reduction (adjusted HR 0.20, 95% CI 0.05-0.72; p=0.014). In exploratory subgroup analyses, TCZ was associated with marked risk reductions in high-risk subgroups: GGO score ≥18 (HR 0.07, 95% CI 0.01-0.36; p=0.002), moderate oxygenation impairment (HR 0.12, 95% CI 0.02-1.00; p=0.05), and elevated inflammatory markers (HR 0.26, 95% CI 0.08-0.82; p=0.021). Tocilizumab also reduced GGO scores (p=0.009). Severe infections occurred in 23.1% (3/13) of the tocilizumab group between post-treatment days 12 and 30.ConclusionIn this small, propensity-matched cohort, while the primary unadjusted analysis did not reach statistical significance, multivariable adjustment revealed a significant survival benefit signal associated with TCZ, particularly in patients with extensive ground-glass opacities or hyperinflammation. These findings suggest that TCZ may offer clinical advantages for specific high-risk AE-IPF subgroups, warranting validation in larger prospective trials.