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JAK Inhibitors for Psoriasis and Psoriatic Arthritis

  • Psoriasis (J Wu, Section Editor)
  • Published:
Current Dermatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Janus kinase (JAK) inhibitors represent a growing class of medications for the targeted treatment of psoriatic disease that can be administered orally or formulated into topical preparations. This article reviews the utility and clinical significance of JAK inhibitors for the treatment of psoriatic disease—both psoriatic arthritis and plaque psoriasis—as demonstrated in clinical trials.

Recent Findings

Tofacitinib, the most widely studied of the JAK inhibitors in psoriatic disease, has demonstrated significant efficacy for the treatment of both psoriatic arthritis and plaque psoriasis. However, while it received approval from the US Food and Drug Association for the former indication, it was denied for the latter. This has not deterred the development of newer JAK inhibitors which hope to provide a balance of efficacy and safety that would allow for their approval. Topical ruxolitinib has also demonstrated efficacy for the treatment of plaque psoriasis.

Summary

JAK inhibitors function by blocking the JAK-STAT pathway, which is crucial to the signaling of the numerous cytokines implicated in the pathogenesis of psoriasis. While oral tofacitinib and topical ruxolitinib are the most well-studied medications for this indication, newer JAK inhibitors—filgotinib and upadacitinib, in particular—are proving promising in more recent clinical trials.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Boutet M-A, Nerviani A, Gallo Afflitto G, Pitzalis C. Role of the IL-23/IL-17 axis in psoriasis and psoriatic arthritis: the clinical importance of its divergence in skin and joints. Int J Mol Sci. 2018;19(2):530.

    Article  PubMed Central  Google Scholar 

  2. Scarpa R. New insights into the concept of psoriatic disease. J Rheumatol Suppl. 2012;89:4–6.

    Article  PubMed  Google Scholar 

  3. Bunte K, Beikler T. Th17 cells and the IL-23/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases. Int J Mol Sci. 2019;20(14):3394.

    Article  CAS  PubMed Central  Google Scholar 

  4. Wcisło-Dziadecka D, Zbiciak-Nylec M, Brzezińska-Wcisło L, Bebenek K, Kaźmierczak A. Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors. Dermatol Ther. 2017;30(6):e12555.

    Article  Google Scholar 

  5. Hsu L, Armstrong AW. JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014.

  6. Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Sign. 2017;15(1):23.

    Article  Google Scholar 

  7. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a TH 17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445(7128):648–51.

    Article  CAS  PubMed  Google Scholar 

  8. de Medeiros AKA, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J. JAK3 as an emerging target for topical treatment of inflammatory skin diseases. PLoS One. 2016;11(10).

  9. Pelechas E, Kaltsonoudis E, Voulgari PV, Drosos AA. Psoriatic arthritis. Illustrated Handbook of Rheumatic and Musculo-Skeletal Diseases. Cham: Springer International Publishing; 2019. p. 93–119.

    Book  Google Scholar 

  10. Benjamin M, McGonagle D. Histopathologic changes at “synovio–entheseal complexes” suggesting a novel mechanism for synovitis in osteoarthritis and spondyloarthritis. Arthritis Rheum. 2007;56(11):3601–9.

    Article  PubMed  Google Scholar 

  11. Veale DJ, McGonagle D, McInnes IB, Krueger JG, Ritchlin CT, Elewaut D, et al. The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis. Rheumatology. 2019;58(2):197–205.

    Article  CAS  PubMed  Google Scholar 

  12. Pfizer announces FDA approval of xeljanz® (tofacitinib) and xeljanz® XR for the Treatment of active psoriatic arthritis: Pfizer Inc.; 2017 [updated 12/14/2017. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_fda_approval_of_xeljanz_tofacitinib_and_xeljanz_xr_for_the_treatment_of_active_psoriatic_arthritis.

  13. •• Mease P, Hall S, FitzGerald O, van der Heijde D, Merola JF, Avila-Zapata F, et al. Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis. N Engl J Med. 2017;377(16):1537–50 This was one of the landmark trials responsible for the approval of tofacitinib for the treatment of psoriatic arthritis. Results demonstrated ACR20 scores for tofacitinib (50% at 5mg BID and 61% at 10mg BID) well above that of placebo (33%) and comparable to that of adalimumab (52%). This approval made JAK inhibitors available for commercial use by dermatologists.

    Article  CAS  PubMed  Google Scholar 

  14. •• Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, et al. Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors. N Engl J Med. 2017;377(16):1525–36 This was another of the landmark trials responsible for the approval of tofacitinib for the treatment of psoriatic arthritis. Results demonstrated ACR20 scores for tofacitinib (50% at 5mg BID and 47% at 10mg BID) that were significantly above that for placebo (24%) at 3 months, with similar results seen for patients receiving tofacitinib continuously for 6 months. This approval made JAK inhibitors available for commercial use by dermatologists.

    Article  CAS  PubMed  Google Scholar 

  15. Nash P, Coates LC, Kivitz AJ, Mease PJ, Gladman DD, Covarrubias-Cobos JA, et al. Safety and efficacy of tofacitinib, an oral Janus kinase inhibitor, up to 36 months in patients with active psoriatic arthritis: data from the third interim analysis of OPAL Balance, an open-label, Long-Term Extension Study. Arthritis Rheumatol. 2018;70.

  16. • Mease P, Coates LC, Helliwell PS, Stanislavchuk M, Rychlewska-Hanczewska A, Dudek A, 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. 2018;392(10162):2367–77 This study reports on results from a phase 2 trial evaluating the efficacy of filgotinib, a selective JAK1 inhibitor, in psoriatic arthritis. It was found that 80% of patients receiving filgotinib achieved ACR20, will above both placebo and scores demonstrated from other JAK inhibitors.

    Article  CAS  PubMed  Google Scholar 

  17. • RINVOQ™ (upadacitinib) Meets Primary and All Ranked Secondary Endpoints in Phase 3 Study in Psoriatic Arthritis: Abbvie; [updated 10/31/2019. Available from: https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-meets-primary-and-all-ranked-secondary-endpoints-in-phase-3-study-in-psoriatic-arthritis.htm. Upadacitinib is the latest commercially available JAK inhibitor that has demonstrated superior efficacy in the treatment of both psoriatic arthritis and plaque psoriasis, as seen in the data presented in this press release. 64% of patients receiving upadacitinib 30mg achieved ACR20 at week 12, and 57% of patients receiving upadacitnib 30mg achieved PASI75 by week 16.

  18. Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2015;173(4):949–61.

    Article  CAS  PubMed  Google Scholar 

  19. Valenzuela F, Korman N, Bissonnette R, Bakos N, Tsai TF, Harper M, et al. Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study. Br J Dermatol. 2018;179(4):853–62.

    Article  CAS  PubMed  Google Scholar 

  20. Merola JF, Elewski B, Tatulych S, Lan S, Tallman A, Kaur M. Efficacy of tofacitinib for the treatment of nail psoriasis: two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2017;77(1):79–87 e1.

    Article  CAS  PubMed  Google Scholar 

  21. Asahina A, Etoh T, Igarashi A, Imafuku S, Saeki H, Shibasaki Y, et al. Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: a randomized, double-blind, phase 3 study. J Dermatol. 2016;43(8):869–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bissonnette R, Iversen L, Sofen H, Griffiths C, Foley P, Romiti R, et al. Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2015;172(5):1395–406.

    Article  CAS  PubMed  Google Scholar 

  23. Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet. 2015;386(9993):552–61.

    Article  CAS  PubMed  Google Scholar 

  24. • Strober B, Gottlieb AB, van de Kerkhof P, Puig L, Bachelez H, Chouela E, et al. Benefit–risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials. Br J Dermatol. 2019;180(1):67–75 This study analyzed the safety of tofacitinib in six clinical trials and concluded that the benefit-risk profile for tofacitinib is similar to that of other systemic agents. This study did note, however, that there is a higher rate of herpes zoster seen in patients treated with tofacitinib.

    Article  CAS  PubMed  Google Scholar 

  25. Ports W, Khan S, Lan S, Lamba M, Bolduc C, Bissonnette R, et al. A randomized phase 2a efficacy and safety trial of the topical J anus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013;169(1):137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ports WC, Feldman SR, Gupta P, Tan H, Johnson TR, Bissonnette R. Randomized pilot clinical trial of tofacitinib solution for plaque psoriasis: challenges of the intra-subject study design. J Drugs Dermatol. 2015;14(8):777–84.

    CAS  PubMed  Google Scholar 

  27. Papp KA, Bissonnette R, Gooderham M, Feldman SR, Iversen L, Soung J, et al. Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a phase 2b randomized clinical trial. BMC Dermatol. 2016;16(1):15.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol. 2012;67(4):658–64.

    Article  CAS  Google Scholar 

  29. Punwani N, Burn T, Scherle P, Flores R, Shi J, Collier P, et al. Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor. Br J Dermatol. 2015;173(4):989–97.

    Article  CAS  PubMed  Google Scholar 

  30. Papp K, Menter M, Raman M, Disch D, Schlichting D, Gaich C, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016;174(6):1266–76.

    Article  CAS  PubMed  Google Scholar 

  31. Bissonnette R, Luchi M, Fidelus-Gort R, Jackson S, Zhang H, Flores R, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral Janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis. J Dermatol Treat. 2016;27(4):332–8.

    Article  CAS  Google Scholar 

  32. Ludbrook V, Hicks K, Hanrott K, Patel J, Binks M, Wyres M, et al. Investigation of selective JAK 1 inhibitor GSK 2586184 for the treatment of psoriasis in a randomized placebo-controlled phase II a study. Br J Dermatol. 2016;174(5):985–95.

    Article  CAS  PubMed  Google Scholar 

  33. Schmieder G, Draelos Z, Pariser D, Banfield C, Cox L, Hodge M, et al. Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study. Br J Dermatol. 2018;179(1):54–62.

    Article  CAS  PubMed  Google Scholar 

  34. Papp K, Pariser D, Catlin M, Wierz G, Ball G, Akinlade B, et al. A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP 015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2015;173(3):767–76.

    Article  CAS  PubMed  Google Scholar 

  35. Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379(14):1313–21.

    Article  CAS  PubMed  Google Scholar 

  36. FDA declines to expand approval of Pfizer arthritis drug: Reuters; 2015 [updated 10/14/2015. Available from: https://www.reuters.com/article/pfizer-psoriasis-fda/fda-declines-to-expand-approval-of-pfizer-arthritis-drug-idUSL1N12E2OW20151014.

  37. FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR): U.S. Food & Drug Administration; 2019 [updated 07/26/2019. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and.

  38. Hosking A-M, Juhasz M, Mesinkovska NA. Topical Janus kinase inhibitors: a review of applications in dermatology. J Am Acad Dermatol. 2018;79(3):535–44.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. SUNY Downstate Health Sciences University, Brooklyn, NY, USA

    Aakaash Varma

  2. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    George Han

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  1. Aakaash Varma
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Correspondence to George Han.

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Conflict of Interest

Dr. George Han reports grants from Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Novartis, MC2, and PellePharm. He also received grants and personal fees from Eli Lilly, Janssen, Pfizer, and UCB. Additionally, Dr. Han received personal fees from Abbvie, LEO Pharma, Ortho Dermatologics, Regeneron, Sanofi Genzyme, and SUN Pharmaceuticals.

Dr. Aakaash Varma declares no conflict of interest.

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Varma, A., Han, G. JAK Inhibitors for Psoriasis and Psoriatic Arthritis. Curr Derm Rep 9, 107–113 (2020). https://doi.org/10.1007/s13671-020-00302-5

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