Clinical relevance of rheumatoid factor and anti‐citrullinated peptides in fibrotic interstitial lung disease

Abstract Background and objective Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti‐citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non‐CTD ILD. Methods A total of 1570 non‐CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA‐ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant‐free survival and incidence of progressive fibrosing‐ILD (PF‐ILD) were compared between seronegative non‐CTD ILD (reference group), seropositive non‐CTD ILD and RA‐ILD using linear mixed‐effect and Cox proportional hazards models adjusted for age, sex, smoking pack‐years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow‐up before and after the treatment. Results Two hundred and seventeen (13.8%) patients with seropositive non‐CTD ILD had similar rates of FVC decline and transplant‐free survival compared to seronegative non‐CTD ILD, but more frequently met the criteria for PF‐ILD (hazard ratio [HR] = 1.35, p = 0.004). RA‐ILD had slower FVC decline ( p = 0.03), less PF‐ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non‐CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non‐CTD ILD. Conclusion Seropositivity in non‐CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression.