Background/Purpose: Interstitial Lung Disease (ILD) is a rare but often severe consequence of several rheumatologic conditions including rheumatoid arthritis (RA). The comparative risk of incident ILD between RA therapies remains undetermined.

Methods: A retrospective cohort study using 2006-2014 Medicare and 2010-2015 Market Scan data was conducted to assess the risk of ILD among biologic and conventional DMARDs (cDMARDs) users. Adults with at least one ICD-9-CM RA diagnosis code from rheumatologist, initiated at least one biologic or cDMARDs were included. Patients had to have at least 1 year of full coverage (medical and pharmacy) prior to their RA treatment. Those with a diagnosis code for prevalent ILD, malignancy, HIV or organ transplantation (MHO), or prior oxygen use (suggesting treatment for pre-existing ILD) were excluded. Patients initiating cDMARDs with prior exposure to biologic or synthetic DMARDS (all available data) were also excluded. Follow up started at the initiation date of each therapy and ended at the earliest of: event, loss of full coverage, end of exposure (with 90 days extension), switch to other biologic or synthetic DMARDS, diagnosis of MHO (except for lung transplant), or end of study. ILD was defined as: one or more hospital discharge diagnosis code (any position) or 2 outpatient diagnosis codes from a physician visit with diagnostic tests for chest CT or lung biopsy. Incidence rates (IR) of ILD were calculated using Poisson regression; hazard ratios (HR) were calculated using COX regression, accounting for the clustering of RA treatments within patients. Among patients who developed ILD, initiation of home oxygen and death (Medicare only) were reported.

Results:  A total of 150,225 RA patients with 208,641 initiations of biologics or DMARDs were eligible for analysis. A total of 958 patients developed ILD among 199,739 person years, resulting in an overall IR of 4.78 per 1,000 person years. The crude IRs for ILD ranged from a low of 3.05 (95%CI: 1.15-8.14) for tofacitinib to a high of 8.37 (7.29-9.61) for infliximab (INF) in Medicare (Table 1); and a low of 0.58 (0.08-4.13) for certolizumab (CER) to 3.87(2.08-7.19) for INF in Market Scan. Compared to abatacept (ABA), the adjusted HR ranged from 0.82 (0.30-2.22) for tofacitinib to 2.07 (1.62-2.64) for INF in Medicare; from 0.41 (0.05, 3.41) for CER to 2.85 (1.03-7.89) for INF in Market Scan.

Among 880 Medicare patients with ILD, 359 (41%) died after a mean (SD) 529 (640) days since diagnosis; 328 (37%) initiated home oxygen, at a mean (SD) of 177 (418) days. Among 78 Market Scan patients with ILD, 22 (28%) initiated oxygen at a mean (SD) of 114(262) days.  

Conclusion: Compared to ABA, INF, rituximab, adalimumab, tocilizumab and etanercept were associated with increased risk of ILD, although the absolute IR differences between therapies were small. Initiation of home oxygen and mortality was high among RA patients with incident ILD.