Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Interstitial lung disease (ILD) is a common extra-articular manifestation of RA,¹ and treatment-induced ILD is more common in Asia than the rest of the world.²

Methods: We aimed to investigate incidence rates (IR; patients [pts] with events per 100 pt-years [PY]) of ILD events in pts with active RA, receiving tofacitinib 5 or 10 mg twice daily in a post hoc analysis of data pooled from 2 Phase (P)1, 10 P2, 7 P3/4, and 2 long-term extension (LTE) trials (ORAL Sequel LTE main study database locked at time of analysis: March 2017). No pts with pre-existing ILD were included. Potential ILD events were adjudicated by three independent pulmonologists as ‘probable’ (compatible adverse event [AE] with supportive clinical evidence) or ‘possible’ (compatible AE with no supportive clinical evidence). ILD IRs at 6-month intervals and by pt age and region are described. A descriptive case-matched control (ratio of pts with vs without ILD events 1:5, matched by age and gender) analysis identified potential ILD risk factors.

Results: Out of 7061 pts (PY of exposure = 23,394), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. The IR for ILD with both doses of tofacitinib treatment was 0.18 (Table; Figure). In a placebo-controlled cohort analysis in tofacitinib P2/3/4 studies, ILD event IRs were numerically lower with tofacitinib vs placebo (Table). IRs were numerically higher in pts aged ≥65 vs <65 years, and in Asian vs non-Asian countries; 95% confidence intervals were wide and overlapped. IRs generally remained stable over time, although the number of events was small in each interval (Figure). There were 17/42 (40.5%) serious AEs of ILD; 35/42 events (83.3%) were mild to moderate in severity. In the case-matched control analysis (case 42 vs control 210), the ILD group had a numerically higher proportion of pts who were Asian (31.0% vs 17.6%), smokers/ex-smokers (50.0% vs 39.5%), RF-positive (89.2% vs 71.0%), anti-CCP antibody positive (54.8% vs 46.7%), had received prior MTX (90.5% vs 79.5%), non-MTX csDMARDs (61.9% vs 55.2%), TNF inhibitors (26.2% vs 18.6%), and concomitant glucocorticoids (71.4% vs 52.9%), and had higher baseline mean ESR (57.0 vs 46.9 mm/hr) and CRP (25.4 vs 15.4 mg/L) vs controls.

Conclusion: Across P1/2/3/4/LTE studies, ILD events following tofacitinib treatment were low, and were associated with known risk factors.

1. Curtis J et al. Arthritis Res Ther 2015; 17: 319.

2. Furukawa H et al. Clin Med Insights Circ Respir Pulm Med 2015; 9 (Suppl 1): 1-7.