Abatacept and Methotrexate may Lower Risk of Interstitial Lung Disease in RA

Jack Cush, MD

Sep 04, 2025 10:00 am

A post hoc, pooled analysis of of rheumatoid arthritis (RA) clinical trials shows those received abatacept had a lower rate of Interstitial lung disease (ILD).

A retrospective analysis of pooled safety data from 10 phase 3 clinical trials of adult RA patients on MTX who were treatd with either ABA or placebo and assess for ILD events (may have included acute respiratory events suggestive of pneumonitis/ILD). Data was drawn from the following trials: AGREE, ATTEST, AIM, ALLOW, ACCOMPANY, ACQUIRE, AVERT, AMPLE, AVERT-2, and early AMPLE. While ILD was not an exclusion criterion for most trials, the AMPLE trial excluded those with severe, progressive, or uncontrolled pulmonary disease. Therefore, some patients may have had pre-existing RA-ILD at baseline.

The analysis compared ABA plus MTX treated (n: 3708 and 10,521 person-years) to placebo plus MTX (n 999, and person-years). Abatacept + MTX had:

lower rate of ILD events (IR 0.10; 0.05–0.18 versus 0.43; 0.16–1.14)
Fewer hospitalizations
lower rates for ILD in: Patients with RA aged ≥ 55 years, body mass index < 30 kg/m², no history of smoking, no baseline disease-modifying antirheumatic drug use other than MTX, no prior tumor necrosis factor inhibitor use, high DAS28-CRP, and rheumatoid factor or anti-citrullinated protein antibody positivity who were receiving corticosteroid(s)

Aggressive combination therapy with ABA and MTX may lower the risk of future ILD. Such findings merit further study and analysis in other cohorts and prospective studies.

Incidence rates of interstitial lung disease events among patients with rheumatoid arthritis treated with abatacept or placebo, with background methotrexate: a post hoc pooled analysis from a compendium of clinical trials