Incidence rates for interstitial lung disease (ILD) events were found to be 0.18 after tofacitinib treatment and are associated with known risk factors in rheumatoid arthritis (RA), according to study data published in JCR: Journal of Clinical Rheumatology.
In a post hoc analysis of 21 clinical trials, researchers assessed incidence rates of ILD events in RA patients receiving tofacitinib, an oral Janus kinase inhibitor, and identified potential risk factors for ILD. Pooled data used in the study included 2 cohorts: the overall cohort of patients receiving tofacitinib 5 or 10 mg twice daily and the randomized controlled cohort of patients receiving either tofacitinib 5 or 10 mg twice daily or placebo. Potential ILD risk factors were identified by a case-matched control analysis that matched patients in the overall cohort who had an ILD event with those who did not.
The overall cohort included 7061 patients who received tofacitinib in phase (P)1, P2, P3, P3b/4, and long-term extension studies. Data of patients with up to 9.5 years of tofacitinib exposure were included in the analysis. A total of 82.6% of patients in the overall cohort were women and had a mean age of 52.1 years. Mean disease duration since diagnosis was 8 years. Of patients in the overall cohort, 42 (0.6%) had an ILD event. Differences in incidence rates (IRs) were observed for age, race, and country of residence. The IRs were higher among patients aged ≥65 years vs those who were younger, and among patients residing in Asian countries vs non-Asian countries.
In the randomized control cohort with 7319 patients, 5824 received tofacitinib. The IRs for ILD events in this group were 0.12 (95% CI, 0.02-0.34) with tofacitinib 5 mg twice daily, 0.10 (0.01-0.36) with tofacitinib 10 mg twice daily, and 0.32 (0.01-1.79) with placebo.
The case-matched control analysis revealed that patients in the ILD events group had known risk factors. Proportionate to the overall group, the ILD events group had a higher number of patients who were Asian, current or previous smokers, had serum markers for RA and inflammation, and had had prior treatment with conventional synthetic disease-modifying antirheumatic drugs and tumor necrosis factor inhibitors. Patients with ILD events showed higher rates of serious infections and had a greater frequency of all-cause mortality (7.1%). Despite this, there was no observed direct relationship between ILD and cause of death.
Rates of ILD events were 0.18 for both doses of tofacitinib and associated with known risk factors for ILD; however, no relationship was observed between dose and ILD events in the overall cohort.
Limitations of the study included the possibility of subclinical and baseline ILD as contributors to IRs, individual physicians’ clinical judgment in ILD assessments, and the results being limited to patients with RA who participated in clinical trials.
Study authors concluded, “These results highlight the importance of accounting for known risk factors of RA-ILD in clinical practice.”
Citera G, Mysler E, Madariaga H, et al. Incidence rates of interstitial lung disease events in tofacitinib-treated rheumatoid arthritis patients. Published online August 20, 2020. JCR: J Clin Rheumatol. doi:10.1097/RHU.0000000000001552