C-reactive protein and ground-glass opacity as predictors for intractable interstitial lung disease in patients with systemic sclerosis under cyclophosphamide treatment regardless of concomitant glucocorticoids

Abstract Objectives Cyclophosphamide (CYC) has been proposed as a standard induction regimen for interstitial lung disease (ILD) associated with systemic sclerosis (SSc). However, there remain patients with SSc-ILD who are intractable to the therapy. This study aimed to identify factors associated with inadequate response to CYC and investigate how to treat SSc-ILD, especially in the need for glucocorticoids (GCs) combined with CYC. Methods This retrospective study included consecutive patients diagnosed with SSc-ILD and treated with CYC between 2009 and 2020. Logistic regression models were used to determine the prognostic factors indicating significant progression of ILD (SP-ILD). The clinical findings of patients treated with vs. without GCs were compared. Results Nineteen patients were registered, with a median age of 61.0 years. Fifteen were females, and five were classified into SP-ILD. Baseline high C-reactive protein (CRP) levels and non-widespread or localized ground-glass opacities (GGOs) predicted SP-ILD in multivariable analyses, and the cut-off level of CRP was 0.41 mg/dL. In clinical courses, SSc-ILD with high inflammation temporarily responded to CYC, regardless of the combined use of GCs; however, the therapeutic effects deteriorated soon after stopping CYC. Conclusion High CRP levels with non-widespread GGO predicted progressive ILD in patients with SSc treated with CYC.