Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients

Abstract

Background/Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. Methods This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as “probable” (supportive clinical evidence) or “possible” (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events. Results Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13–5.21]), current smokers (2.89 [1.33–6.26]), and Disease Activity Score in 28 joints–erythrocyte sedimentation rate score (1.30 [1.04–1.61]) as significant risk factors for ILD events. Conclusions Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.

Baricitinib and the Risk of Incident Interstitial Lung Disease: A Descriptive Clinical Case Report from Clinical Trials

“…Tofacitinib, also an oral Janus kinase inhibitor, reported a similar incidence rate of 0.18 per 100 PYE for non-infectious chronic ILD at both doses of 5 mg and 10 mg daily. In the tofacitinib analysis, the median onset time of ILD from the starting of treatment in RA patients was 1144 days, also comparable with our current analysis (range, 60-1740 days) [21]. JAK inhibition has been associated with infections mainly of the upper respiratory and urinary tract [22].…”

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease

“…Even less is understood about Janus kinase inhibition in patients with bronchiectasis. While post hoc analysis of phase 2, 3 and 3b/4 clinical trials indicates that the de novo incidence of interstitial lung disease is low in patients with rheumatoid arthritis treated with JAKi [21]; to our knowledge, no study has yet examined the pulmonary tolerance and safety of JAKi in those with existing ILD or bronchiectasis. The current study sought to address this important clinical scenario, by comparing time to respiratory events in patients receiving JAKi with patients receiving the current, best-practice medication for this clinical cohort, rituximab.…”

Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis

“…A post hoc analysis on 7061 RA patients receiving tofacitinib from clinical trials and long-term extension studies reported an incidence rate for ILD with both tofacitinib doses of 0.18 per 100 patient-years [ 17 ].…”