Tofacitinib May Reduce Risk of Interstitial Lung Disease in Patients With RA


Compared with other bDMARDs, patients with rheumatoid arthritis treated with tofacitinib had a 4-fold reduced incidence of interstitial lung disease.

Patients with rheumatoid arthritis (RA) who were treated with tofacitinib reported the lowest incidence of interstitial lung disease (ILD) when compared with all other biologic disease-modifying antirheumatic drugs (bDMARDs) analyzed, according to a study published in JAMA Network Open.1 After adjusting for specific covariates, patients receiving tofacitinib also had a reduced risk of ILD when compared with those receiving adalimumab.

Tofacitinib May Reduce Risk of Interstitial Lung Disease in Patients With RA

Matthew C Baker, MD, MS

Image Credit: Stanford University

ILD develops in approximately 10% of patients with RA, with risk factors including smoking, rheumatoid factor or anti-cyclic citrullinated peptide autoantibodies, and certain genetic variants.2

“Clinicians must determine the best therapy to control a patient’s joint disease, while at the same time minimize the potential risk of pulmonary toxic effects in these patients with already compromised lung function,” wrote Matthew C Baker, MD, MS, Clinical Chief in the Division of Immunology and Rheumatology at Stanford University, and a team of investigators. “Current data are lacking regarding the risk of bDMARD and targeted synthetic DMARD (tsDMARD) use on the development of ILD in patients with RA.”

A retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019 was conducted to analyze the risk of developing ILD in adult patients with RA receiving treatment with different bDMARDs or tsDMARDs.

The primary endpoint was incident ILD. The incidence rates (IRs) for the development of ILD were analyzed and the risk of ILD for specific b/tsDMARDs was compared using Cox-regression models.

Tofacitinib was linked to a reduced risk of developing ILD when compared with adalimumab in the primary analysis. However, the drug is usually prescribed as a third-line agent after adalimumab, which may cause inherent biases. Therefore, a sensitivity analysis compared these treatments using a prevalent new-user cohort design.

Eligible patients were adults with RA with 1 year or more of continuous enrollment treated with a b/tsDMARD of interest without a preexisting ILD diagnosis. DMARDs included tofacitinib, tocilizumab, rituximab, adalimumab, and abatacept.

In total, 28,559 patients with RA were included in the analysis. The mean age was 55.6 years and 78% (n=22,158) were female. Of these patients, 13,326 were treated with adalimumab, 5676 received abatacept, 5444 were in the rituximab group, 2548 were in the tocilizumab cohort, and 1565 were treated with tofacitinib.

A total of 276 incident cases of ILD developed during the follow-up period. Compared with other bDMARDs, patients treated with tofacitinib had a 4-fold reduced incidence of ILD. The crude IRs per 1000 person-years for ILD were reported as 6.15 (95% confidence interval [CI] 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, 4.46 (95% CI 3.44-5.70) for abatacept, 3.43 (95% CI 2.85-4.09) for adalimumab, and only 1.47 (95% CI 0.54-3.27) for tofacitinib.

An adjusted model showed a 69% reduced risk of ILD in the tofacitinib group compared with adalimumab-treated patients (adjusted hazard ratio [aHR] 0.31; 95% CI 0.12 – 0.78; P = .009). Further, after propensity score matching in the prevalent new-user cohort design, analysis reported that the incidence rate per 1000 person-years of ILD for patients receiving tofacitinib was 1.48 (95% CI, 0.54 – 3.28), compared with 4.30 (95% CI, 3.15 – 5.74) in the adalimumab group.

In the adjusted model, patients treated with tofacitinib had a 68% reduced risk of developing ILD when compared with the adalimumab cohort (adjusted hazard ratio [aHR] 0.32; 95% CI 0.13 – 0.82; P <.001).

“Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA,” investigators concluded. “These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.”


  1. 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. Published 2023 Mar 1. doi:10.1001/jamanetworkopen.2023.3640
  2. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study.Arthritis Rheum. 2010;62(6):1583-1591. doi:10.1002/art.27405
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