Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Selective Janus kinase inhibitors come of age

Janus kinase (JAK) inhibitors (jakinibs) that target downstream signalling by a large range of cytokines are effective in treating autoimmune and rheumatic diseases. Newer jakinibs that selectively inhibit individual JAKs and a narrower spectrum of cytokines have now been developed, but how do these inhibitors compare with existing drugs?

Key advances

  • Filgotinib, a JAK1-selective inhibitor, demonstrates efficacy in psoriatic arthritis with no unexpected safety signals1.

  • Filgotinib is efficacious in patients with ankylosing spondylitis who did not respond to nonsteroidal anti-inflammatory drugs2.

  • Two phase III trials demonstrate efficacy of upadacitinib, a selective JAK1, in RA3,4.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Selectivity of JAK inhibitors.


  1. Mease, P. et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 392, 2367–2377 (2018).

    Article  CAS  Google Scholar 

  2. van der Heijde, D. et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet 392, 2378–2387 (2018).

    Article  Google Scholar 

  3. Burmester, G. R. et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 391, 2503–2512 (2018).

    Article  CAS  Google Scholar 

  4. Genovese, M. C. et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet 391, 2513–2524 (2018).

    Article  CAS  Google Scholar 

  5. Gadina, M. et al. Translational and clinical advances in JAK-STAT biology: the present and future of jakinibs. J. Leukoc. Biol. 104, 499–514 (2018).

    Article  CAS  Google Scholar 

  6. Winthrop, K. L. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat. Rev. Rheumatol. 13, 234–243 (2017).

    Article  CAS  Google Scholar 

  7. Papp, K. et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N. Engl. J. Med. 379, 1313–1321 (2018).

    Article  CAS  Google Scholar 

  8. Dengler, H. S. et al. Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma. Sci. Transl. Med. 10, eaao2151 (2018).

    Article  Google Scholar 

  9. Barroso, N. S., Miller, E. Z. & Furst, D. E. A case series on patients on tofacitinib in combination with a biologic. J. Clin. Rheumatol. 24, 349–351 (2018).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to John J. O’Shea.

Ethics declarations

Competing interests

J.J.O’S. declares that he and the NIH hold a patent related to JAK inhibition in autoimmune disease and receive royalties from this patent. Both authors declare that they have a Collaborative Research and Development Agreement related to JAK inhibitors with Pfizer.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

O’Shea, J.J., Gadina, M. Selective Janus kinase inhibitors come of age. Nat Rev Rheumatol 15, 74–75 (2019).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing