Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis

Nat Commun. 2022 Jun 6;13(1):3140. doi: 10.1038/s41467-022-30615-x.


Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4+ T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytokines / metabolism
  • Humans
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Pyrimidines* / pharmacology
  • Pyrimidines* / therapeutic use
  • Sarcoidosis* / drug therapy
  • Sarcoidosis* / pathology


  • Cytokines
  • Piperidines
  • Pyrimidines
  • tofacitinib

Associated data