Arthritis Research & Therapy (2015) 17:319 DOI: 10.1186/s13075-015-0835-7Interstitial lung disease (ILD) is a common extra-articular condition for RA patients. This retrospective cohort study of health insurance databases investigates the ILD incidence and exacerbation between ABA, TCZ, RTX, and anti-TNFα agents in adult RA patients with prior biologic therapy. Two definitions of ILD were used: one specific, one sensitive; descriptive results were produced for both. In patients with no history of ILD, the overall incidence rate of ILD ranged from 1.8% to 6.4% (depending upon the definition used), and those over the age of 65, male, with recent exposure to glucocorticoids, or with a baseline history of other pulmonary conditions were at increased risk of ILD. ILD hospitalization events ranged from 65.8 to 127.7 per 1000 PY, using the specific and sensitive definitions, respectively. Recent exposure to MTX was associated with a significant reduction in ILD-related hospitalization, while being male or having prior hospitalizations for asthma or ILD/pneumonia significantly increased risk. There were significant baseline differences between patients exposed to alternate MOA compared to patients exposed to anti-TNFs. This study did not find exposure to T-cell, B-cell, or IL-6 inhibitors to present significantly increased ILD risk compared to anti-TNFα agents.