Tofacitinib Associated With Lower Incidence of Interstitial Lung Disease in RA

Compared with other DMARDs, the JAK inhibitor tofacitinib was found to be associated with a reduced risk for interstitial lung disease.

In rheumatoid arthritis (RA), the risk of developing interstitial lung disease (ILD) is lower among patients receiving tofacitinib compared with those receiving other biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs), according to study findings published in JAMA Network Open.

The prevalence of ILD in RA is approximately 10%, and some evidence has suggested that RA treatments may worsen underlying ILD.

To evaluate the association between RA treatments and ILD, researchers from Stanford University conducted a retrospective cohort study using data from the Optum Clinformatics Data Mart Database.

Patients with RA receiving b/tsDMARDs between 2003 and 2019 were evaluated for incidence of ILD.

A total of 28,559 patients with RA, with a mean age of 55.6 (SD, 13.7) years were included in the study; 77.6% were women; and 70.7% were White. The majority of patients (46.6%) were receiving adalimumab, followed by abatacept, rituximab, tocilizumab, and tofacitinib.

[T]reatment with tofacitinib, and perhaps other Janus kinase inhibitors, may provide benefit in reducing the risk of developing RA-ILD.

During a median follow-up of 1.6 years, a total of 276 ILD cases were reported. The crude incidence rate (IR) of ILD was 4.11 per 1000 person-years (py) overall.

Stratified by b/tsDMARDs, the IR was highest among those who received rituximab (IR, 6.15 per 1000 py) and lowest among those who received tofacitinib (IR, 1.47 per 1000 py).

After adjusting for age, sex, race, and the use of immunosuppressive treatments, the risk for ILD was similar with other RA treatments, except tofacitinib (adjusted hazard ratio [aHR], 0.31; 95% CI, 0.12-0.78; P =.009), compared with adalimumab.

In a sensitivity analysis, risk for ILD was compared between 4677 patients who received adalimumab and 1559 received tofacitinib. The findings were consistent with the main analysis, in which the ILD IRs were 4.30 per 1000 py for adalimumab and 1.48 per 1000 py for tofacitinib. Compared with adalimumab, tofacitinib had a reduced risk for ILD (aHR, 0.32; 95% CI, 0.13-0.82; P <.001).

Overall, the researchers found that among all the b/tsDMARDs studied, ILD incidence was lowest with tofacitinib.

A major limitation of the study was the lack of data about ILD risk factors, such as smoking and genetic predisposition.

However, the study authors concluded, “These results suggest that treatment with tofacitinib, and perhaps other Janus kinase inhibitors, may provide benefit in reducing the risk of developing RA-ILD.”


Baker MC, Liu Y, Lu R, Lin J, Melehani J, Robinson WH. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640. doi:10.1001/jamanetworkopen.2023.3640