Window of opportunity with abatacept in Rheumatoid arthritis-associated interstitial lung disease: A multicentre study of 526 patients.

Abstract

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major cause of morbidity and mortality, and optimal treatment strategies remain unclear. Abatacept (ABA) is supported by observational evidence, but the impact of early initiation on pulmonary outcomes is unknown. We conducted a national multicentre observational cohort including 526 patients with RA-ILD treated with ABA across 40 Spanish hospitals. Patients were classified as early (ABA within 6 months of ILD diagnosis) or late (ABA ≥24 months after diagnosis). Longitudinal changes in forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), high-resolution CT (HRCT), dyspnoea, RA activity, glucocorticoid use, safety, and drug retention were analysed using mixed-effects models adjusted for confounders. Timing of ABA initiation was evaluated both categorically and continuously. Median follow-up was 24 [8-48] months. Pulmonary function remained stable: 77% of patients showed improvement or stabilisation in FVC and 72% in DLCO, while HRCT improved or stabilised in 69%. No significant differences were observed between early and late groups in FVC or DLCO. However, each additional month of delay in ABA initiation was associated with greater DLCO decline (β=-0.002402; 95% CI -0.004287 to -0.000517; p = 0.013), equivalent to an additional 2-3% annual loss per year of delay. No association was found for FVC. DAS28-ESR decreased and prednisone dose was reduced. ABA retention was 83% with a favourable safety profile. ABA stabilised lung function, improved RA control, and reduced glucocorticoid use. Earlier initiation was associated with better DLCO preservation in adjusted analyses, suggesting a possible pulmonary 'window of opportunity' in RA-ILD that warrants confirmation in future prospective studies.