Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials

J Clin Rheumatol. 2021 Dec 1;27(8):e482-e490. doi: 10.1097/RHU.0000000000001552.


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.

MeSH terms

  • Aged
  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / epidemiology
  • Humans
  • Incidence
  • Lung Diseases, Interstitial* / chemically induced
  • Lung Diseases, Interstitial* / diagnosis
  • Lung Diseases, Interstitial* / epidemiology
  • Piperidines
  • Pyrimidines
  • Pyrroles / adverse effects
  • Treatment Outcome


  • Antirheumatic Agents
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • tofacitinib