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Objective To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. Results We studied 263 RA-ILD patients (mean ± s. d. age 64.6 ± 10 years) [ABAMONO (n  = 111), ABAMTX (n  = 46) and ABANON-MTX (n  = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5–15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. Conclusion In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA. [ABSTRACT FROM AUTHOR]