American Journal of Clinical Dermatology

, Volume 20, Issue 2, pp 181–192 | Cite as

JAK Inhibitors for Atopic Dermatitis: An Update

  • Helen He
  • Emma Guttman-YasskyEmail author
Leading Article


Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of T helper (Th) 2, Th22, and varying degrees of Th1 and Th17 among various subtypes. The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and spleen tyrosine kinase (SYK) pathways are involved in signaling of several AD-related cytokines, such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17, mediating downstream inflammation and barrier alterations. While AD is primarily Th2-driven, the clinical and molecular heterogeneity of AD endotypes highlights the unmet need for effective therapeutic options that target more than one immune axis and are safe for long-term use. The JAK inhibitors, which target different combinations of kinases, have overlapping but distinct mechanisms of action and safety profiles. Several topical and oral JAK inhibitors have been shown to decrease AD severity and symptoms. A review of the JAK and SYK inhibitors that are currently undergoing evaluation for efficacy and safety in the treatment of AD summarizes available data on a promising area of therapeutics and further elucidates the complex molecular interactions that drive AD.


Compliance with Ethical Standards

Conflict of interest

EG-Y is an employee of Mount Sinai and has received research funds (grants paid to the institution) from Abbvie, Celgene, Galderma, Glenmark, Janssen Biotech, LEO Pharmaceuticals, Novartis, Pfizer, Regeneron, Asana, DS Biopharma, Innovvaderm, Ralexar, and Novan. She receives consulting fees/honorarium from AbbVie, Celgene, Dermira, Galderma, Glenmark, Novartis, Pfizer, Regeneron, Sanofi, Mitsubishi Tanabe, Eli Lilly, Asana, Kyowa Kirin, Allergan, DS Bipharma, and Concert. She serves on the advisory board for Celgene, Dermira, Galderma, Glenmark, LEO Pharma, Novartis, Pfizer, Sanofi, Regeneron, Eli Lilly, Asana, Kyowa Kirin, Allergan, DBV, Escalier, and Dermavant. HH has no conflict of interest.


No funds were received for preparation of this review.


  1. 1.
    Leung DY. New insights into atopic dermatitis: role of skin barrier and immune dysregulation. Allergol Int. 2013;62(2):151–61.CrossRefPubMedGoogle Scholar
  2. 2.
    Renert-Yuval Y, Guttman-Yassky E. Systemic therapies in atopic dermatitis: the pipeline. Clin Dermatol. 2017;35(4):387–97.CrossRefPubMedGoogle Scholar
  3. 3.
    Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175(5):902–11.CrossRefPubMedGoogle Scholar
  5. 5.
    Simpson EL, Bieber T, Eckert L, Wu R, Ardeleanu M, Graham NM, et al. Patient burden of moderate to severe atopic dermatitis (AD): Insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol. 2016;74(3):491–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233–46.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol. 2017;139(6):1723–34.CrossRefPubMedGoogle Scholar
  8. 8.
    Czarnowicki T, Gonzalez J, Shemer A, Malajian D, Xu H, Zheng X, et al. Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population. J Allergy Clin Immunol. 2015;136(1):104–15 e7.Google Scholar
  9. 9.
    Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3):110.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gittler JK, Shemer A, Suárez-Fariñas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQF, et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344–54.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Werfel T, Allam J-P, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(2):336–49.CrossRefPubMedGoogle Scholar
  12. 12.
    Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4S):S65–76.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Brunner PM, Leung DYM, Guttman-Yassky E. Immunologic, microbial, and epithelial interactions in atopic dermatitis. Ann Allergy Asthma Immunol. 2018;120(1):34–41.CrossRefPubMedGoogle Scholar
  14. 14.
    Suarez-Farinas M, Ungar B, Correa da Rosa J, Ewald DA, Rozenblit M, Gonzalez J, et al. RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications. J Allergy Clin Immunol. 2015;135(5):1218–27.Google Scholar
  15. 15.
    Esaki H, Ewald DA, Ungar B, Rozenblit M, Zheng X, Xu H, et al. Identification of novel immune and barrier genes in atopic dermatitis by laser capture micro-dissection. J Allergy Clin Immunol. 2015;135(1):153–63.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Czarnowicki T, Gonzalez J, Bonifacio KM, Shemer A, Xiangyu P, Kunjravia N, et al. Diverse activation and differentiation of multiple B-cell subsets in patients with atopic dermatitis but not in patients with psoriasis. J Allergy Clin Immunol. 2016;137(1):118–29 e5.Google Scholar
  17. 17.
    Ungar B, Garcet S, Gonzalez J, Dhingra N, Correa da Rosa J, Shemer A, et al. An integrated model of atopic dermatitis biomarkers highlights the systemic nature of the disease. J Invest Dermatol. 2017;137(3):603–13.Google Scholar
  18. 18.
    Schmitt J, Langan S, Williams HC. What are the best outcome measurements for atopic eczema? A systematic review. J Allergy Clin Immunol. 2007;120(6):1389–98.CrossRefPubMedGoogle Scholar
  19. 19.
    Chopra R, Vakharia PP, Sacotte R, Patel N, Immaneni S, White T, et al. Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis. Br J Dermatol. 2017;177(5):1316–21.CrossRefPubMedGoogle Scholar
  20. 20.
    Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Hamilton JD, Suárez-Fariñas M, Dhingra N, Cardinale I, Li X, Kostic A, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014;134(6):1293–300.CrossRefPubMedGoogle Scholar
  22. 22.
    Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. Epub 2018 Jun 12.
  23. 23.
    Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, Taieb A, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863–71.CrossRefPubMedGoogle Scholar
  24. 24.
    Kabashima K, Furue M, Hanifin JM, Pulka G, Wollenberg A, Galus R, et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: Randomized, phase II, long-term extension study. J Allergy Clin Immunol. 2018;S0091–6749(18):30698-5.Google Scholar
  25. 25.
    Guttman-Yassky E, Khattri S, Brunner PM, Neumann A, Malik K, Fuentes-Duculan J, et al. A pathogenic role for Th22/IL-22 in atopic dermatitis is established by a placebo-controlled trial with an anti IL-22/ILV-094 mAb [abstract no. 313]. J Invest Dermatol. 2017;137(5):S53.Google Scholar
  26. 26.
    Khattri S, Brunner PM, Garcet S, Finney R, Cohen SR, Oliva M, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26(1):28–35.CrossRefPubMedGoogle Scholar
  27. 27.
    Samrao A, Berry TM, Goreshi R, Simpson EL. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol. 2012;148(8):890–7.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Saporito RC, Cohen DJ. Apremilast use for moderate-to-severe atopic dermatitis in pediatric patients. Case Rep Dermatol. 2016;8(2):179–84.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Bantz SK, Zhu Z, Zheng T. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol. 2014;5(2):202.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Kezic S, O’Regan GM, Lutter R, Jakasa I, Koster ES, Saunders S, et al. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. J Allergy Clin Immunol. 2012;129(4):1031–9.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Leung DYM, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769–79.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Esaki H, Brunner PM, Renert-Yuval Y, Czarnowicki T, Huynh T, Tran G, et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol. 2016;138(6):1639–51.CrossRefPubMedGoogle Scholar
  33. 33.
    Brunner PM, Israel A, Zhang N, Leonard A, Wen H-C, Huynh T, et al. Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations. J Allergy Clin Immunol. 2018;141(6):2094–106.CrossRefPubMedGoogle Scholar
  34. 34.
    Czarnowicki T, Esaki H, Gonzalez J, Malajian D, Shemer A, Noda S, et al. Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets. J Allergy Clin Immunol. 2015;136(4):941–51 e3.Google Scholar
  35. 35.
    Brunner PM, Suárez-Fariñas M, He H, Malik K, Wen HC, Gonzalez J, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017;7:8707.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Noda S, Suarez-Farinas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015;136(5):1254–64.CrossRefPubMedGoogle Scholar
  37. 37.
    Wen H-C, Czarnowicki T, Noda S, Malik K, Pavel AB, Nakajima S, et al. Serum from Asian patients with atopic dermatitis is characterized by TH2/TH22 activation, which is highly correlated with nonlesional skin measures. J Allergy Clin Immunol. 2018;142(1):324–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Sanyal RD, Pavel AB, Glickman J, Chan TC, Zheng X, Zhang N, et al. Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation. Ann Allergy Asthma Immunol. Epub 2018 Sep 14.
  39. 39.
    Suarez-Farinas M, Dhingra N, Gittler J, Shemer A, Cardinale I, de Guzman Strong C, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132(2):361–70.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Martel BC, Litman T, Hald A, Norsgaard H, Lovato P, Dyring-Andersen B, et al. Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis. Exp Dermatol. 2016;25(6):453–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Cotter DG, Schairer D, Eichenfield L. Emerging therapies for atopic dermatitis: JAK inhibitors. J Am Acad Dermatol. 2018;78(3S1):S53–S62.Google Scholar
  42. 42.
    O’Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36(4):542–50.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Németh T, Virtic O, Sitaru C, Mócsai A. The Syk tyrosine kinase is required for skin inflammation in an in vivo mouse model of epidermolysis bullosa acquisita. J Invest Dermatol. 2017;137(10):2131–9.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Abdel-Magid AF. Spleen tyrosine kinase inhibitors (SYK) as potential treatment for autoimmune and inflammatory disorders: patent highlight. ACS Med Chem Lett. 2013;4(1):18–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Pernis AB, Rothman PB. JAK-STAT signaling in asthma. J Clin Invest. 2002;109(10):1279–83.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Riley JK, Takeda K, Akira S, Schreiber RD. Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action. J Biol Chem. 1999;274(23):16513–21.Google Scholar
  47. 47.
    O’Shea JJ, Steward-Tharp SM, Laurence A, Watford WT, Wei L, Adamson AS, et al. Signal transduction and Th17 cell differentiation. Microbes Infect. 2009;11(5):599–611.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kontzias A, Kotlyar A, Laurence A, Changelian P, O’Shea JJ. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012;12(4):464–70.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Stritesky GL, Muthukrishnan R, Sehra S, Goswami R, Pham D, Travers J, et al. The transcription factor STAT3 is required for T helper 2 cell development. Immunity. 2011;34(1):39–49.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S-i, et al. Essential role of Stat6 in IL-4 signalling. Nature. 1996;380(6575):627–30.Google Scholar
  51. 51.
    Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2(3):e24137.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Goswami R, Jabeen R, Yagi R, Pham D, Zhu J, Goenka S, et al. STAT6-dependent regulation of Th9 development. J Immunol. 2012;188(3):968–75.CrossRefPubMedGoogle Scholar
  53. 53.
    Goenka S, Kaplan MH. Transcriptional regulation by STAT6. Immunol Res. 2011;50(1):87–96.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Tamura K, Arakawa H, Suzuki M, Kobayashi Y, Mochizuki H, Kato M, et al. Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases. Clin Exp Allergy. 2001;31(10):1509–14.CrossRefPubMedGoogle Scholar
  55. 55.
    Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008;126(3):332–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Ishizaki M, Akimoto T, Muromoto R, Yokoyama M, Ohshiro Y, Sekine Y, et al. Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. J Immunol. 2011;187(1):181–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Papp K, Gordon K, Thaci 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.CrossRefPubMedGoogle Scholar
  58. 58.
    Lehtonen A, Matikainen S, Julkunen I. IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells. J Leukoc Biol. 2005;79(6):1279–85.Google Scholar
  59. 59.
    Alonzi T, Maritano D, Gorgoni B, Rizzuto G, Libert C, Poli V. Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene inactivation [correction of activation] in the liver. Mol Cell Biol. 2001;21(5):1621–32.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15(4):234–48.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Wang Y, van Boxel-Dezaire AH, Cheon H, Yang J, Stark GR. STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor. Proc Natl Acad Sci USA. 2013;110(42):16975–80.CrossRefPubMedGoogle Scholar
  62. 62.
    Li HS, Yang CY, Nallaparaju KC, Zhang H, Liu Y-J, Goldrath AW, et al. The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development. Blood. 2012;120(22):4363–73.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, O’Malley JT, et al. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol. 2007;178(8):4901–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 2007;26(3):371–81.CrossRefPubMedGoogle Scholar
  65. 65.
    Malin S, McManus S, Cobaleda C, Novatchkova M, Delogu A, Bouillet P, et al. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol. 2010;11(2):171–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Mahmud SA, Manlove LS, Farrar MA. Interleukin-2 and STAT5 in regulatory T cell development and function. JAKSTAT. 2013;2(1):e23154.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Tripathi P, Kurtulus S, Wojciechowski S, Sholl A, Hoebe K, Morris SC, et al. STAT5 is critical to maintain effector CD8+ T cell responses. J Immunol. 2010;185(4):2116–24.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171(1):217–28.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Fukuyama T, Ganchingco JR, Mishra SK, Olivry T, Rzagalinski I, Volmer DA, et al. Janus kinase inhibitors display broad anti-itch properties: a possible link through the TRPV1 receptor. J Allergy Clin Immunol. 2017;140(1):306–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Wu NL, Huang DY, Tsou HN, Lin YC, Lin WW. Syk mediates IL-17-induced CCL20 expression by targeting Act1-dependent K63-linked ubiquitination of TRAF6. J Invest Dermatol. 2015;135(2):490–8.CrossRefPubMedGoogle Scholar
  71. 71.
    Wu NL, Huang DY, Wang LF, Kannagi R, Fan YC, Lin WW. Spleen tyrosine kinase mediates EGFR signaling to regulate keratinocyte terminal differentiation. J Invest Dermatol. 2016;136(1):192–201.CrossRefPubMedGoogle Scholar
  72. 72.
    Ackermann JA, Nys J, Schweighoffer E, McCleary S, Smithers N, Tybulewicz VLJ. Syk tyrosine kinase is critical for B cell antibody responses and memory B cell survival. J Immunol. 2015;194(10):4650–6.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Whitney PG, Bär E, Osorio F, Rogers NC, Schraml BU, Deddouche S, et al. Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection. PLoS Pathog. 2014;10(7):e1004276.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Meyer DM, Jesson MI, Li X, Elrick MM, Funckes-Shippy CL, Warner JD, et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond). 2010;7:41.CrossRefPubMedCentralGoogle Scholar
  75. 75.
    Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol. 2011;186(7):4234–43.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Kubo S, Nakayamada S, Sakata K, Kitanaga Y, Ma X, Lee S, et al. Janus kinase inhibitor baricitinib modulates human innate and adaptive immune system. Front Immunol. 2018;9:1510.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Krueger J, Clark JD, Suarez-Farinas M, Fuentes-Duculan J, Cueto I, Wang CQ, et al. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: a randomized phase 2 study. J Allergy Clin Immunol. 2016;137(4):1079–90.CrossRefPubMedGoogle Scholar
  78. 78.
    Ghoreschi K, Gadina M. Jakpot! New small molecules in autoimmune and inflammatory diseases. Exp Dermatol. 2014;23(1):7–11.CrossRefPubMedGoogle Scholar
  79. 79.
    Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495–507.CrossRefPubMedGoogle Scholar
  80. 80.
    Machado MAA, Moura CS, Guerra SF, Curtis JR, Abrahamowicz M, Bernatsky S. Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study. Arthritis Res Ther. 2018;20(1):60.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370(25):2377–86.CrossRefPubMedGoogle Scholar
  82. 82.
    Hosking AM, Juhasz M, Mesinkovska NA. Topical Janus kinase inhibitors: a review of applications in dermatology. J Am Acad Dermatol. 2018;79(3):535–44.CrossRefPubMedGoogle Scholar
  83. 83.
    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.CrossRefPubMedGoogle Scholar
  84. 84.
    Sandborn WJ, Su C, Panes J. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;377(5):496–7.CrossRefPubMedGoogle Scholar
  85. 85.
    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.CrossRefPubMedGoogle Scholar
  86. 86.
    Papp KA, Krueger JG, Feldman SR, Langley RG, Thaci D, Torii H, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. J Am Acad Dermatol. 2016;74(5):841–50.CrossRefPubMedGoogle Scholar
  87. 87.
    Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol. 2017;76(1):22–8.CrossRefPubMedGoogle Scholar
  88. 88.
    Reuters. FDA declines to expand approval of Pfizer arthritis drug [press release]. 2015 Oct 4. Accessed 3 Oct 2018.
  89. 89.
    Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015;73(3):395–9.CrossRefPubMedGoogle Scholar
  90. 90.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Bagherani N, Smoller BR. Efficacy of topical tofacitinib, a Janus kinase inhibitor, in the treatment of plaque psoriasis. Dermatol Ther. Epub 2017 Jan 30.
  92. 92.
    Ports WC, Khan S, Lan S, Lamba M, Bolduc C, Bissonnette R, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013;169(1):137–45.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 2010;184(9):5298–307.CrossRefPubMedGoogle Scholar
  94. 94.
    Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243–52.CrossRefPubMedGoogle Scholar
  95. 95.
    Fleischmann R, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506–17.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Dougados M, van der Heijde D, Chen YC, Greenwald M, Drescher E, Liu J, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017;76(1):88–95.CrossRefPubMedGoogle Scholar
  97. 97.
    Tanaka Y, Emoto K, Cai Z, Aoki T, Schlichting D, Rooney T, et al. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis receiving background methotrexate therapy: a 12-week, double-blind, randomized placebo-controlled study. J Rheumatol. 2016;43(3):504–11.CrossRefPubMedGoogle Scholar
  98. 98.
    Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y, et al. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine. 2015;2(4):351–5.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, 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.CrossRefPubMedGoogle Scholar
  100. 100.
    Wallace DJ, Furie RA, Tanaka Y, Kalunian KC, Mosca M, Petri MA, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018;392(10143):222–31.CrossRefPubMedGoogle Scholar
  101. 101.
    Guttman-Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. Epub 2018 Feb 1.
  102. 102.
    Scott IC, Hider SL, Scott DL. Thromboembolism with Janus kinase (JAK) inhibitors for rheumatoid arthritis: how real is the risk? Drug Saf. 2018;41(7):645–53.CrossRefPubMedGoogle Scholar
  103. 103.
    Kunwar S, Collins CE, Constantinescu F. Baricitinib, a Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2018;37(10):2611–20.CrossRefPubMedGoogle Scholar
  104. 104.
    Vazquez ML, Kaila N, Strohbach JW, Trzupek JD, Brown MF, Flanagan ME, et al. Identification of N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfo namide (PF-04965842): a selective JAK1 clinical candidate for the treatment of autoimmune diseases. J Med Chem. 2018;61(3):1130–52.CrossRefPubMedGoogle Scholar
  105. 105.
    Mohamed MF, Camp HS, Jiang P, Padley RJ, Asatryan A, Othman AA. Pharmacokinetics, safety and tolerability of ABT-494, a novel selective JAK 1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis. Clin Pharmacokinet. 2016;55(12):1547–58.CrossRefPubMedGoogle Scholar
  106. 106.
    Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, et al. Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheumatol. 2016;68(12):2857–66.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Kremer JM, Emery P, Camp HS, Friedman A, Wang L, Othman AA, et al. A phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-tumor necrosis factor therapy. Arthritis Rheumatol. 2016;68(12):2867–77.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Peeva E, Hodge MR, Kieras E, Vazquez ML, Goteti K, Tarabar SG, et al. Evaluation of a Janus Kinase 1 inhibitor, PF-04965842, in healthy subjects: a phase 1, randomized, placebo-controlled, dose-escalation study. Br J Clin Pharmacol. 2018;84(8):1776–88.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Schmieder GJ, Draelos ZD, Pariser DM, 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. 2017;179(1):54–62.CrossRefGoogle Scholar
  110. 110.
    Wright HL, Cross AL, Edwards SW, Moots RJ. Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo. Rheumatology (Oxford). 2014;53(7):1321–31.CrossRefPubMedGoogle Scholar
  111. 111.
    Sandborn WJ, Feagan BG, Panes J, D’Haens GR, Colombel JF, Zhou Q, et al. Safety and efficacy of ABT-494 (upadacitinib), an oral Jak1 inhibitor, as induction therapy in patients with Crohn’s disease: results from Celest. Gastroenterology. 2017;152(5):S1308–9.CrossRefGoogle Scholar
  112. 112.
    Thaci D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387(10013):40–52.CrossRefPubMedGoogle Scholar
  113. 113.
    Guttman-Yassky E, Anderson J, APangan A, Silverberg JI, Thaçi D, Hong C, et al. Primary results from a phase 2b, randomized, placebo-controlled trial of upadacitinib for patients with atopic dermatitis [abstract]. American Academy of Dermatology Annual Meeting; 16–20 Feb 2018; San Diego.Google Scholar
  114. 114.
    AbbVie. AbbVie’s upadacitinib (ABT-494) meets primary endpoint in phase 2b study in atopic dermatitis [press release]. 2017 Sep 7. Accessed 3 Oct 2018.
  115. 115.
    Rao NS, Reddy S, Sandeep G, Damle NK, Aranapakam VM, Thompson S, et al. ASN002: a potent dual SYK/JAK inhibitor currently in a phase I/II study shows strong antitumor activity in preclinical studies [abstract]. Blood. 2015;126(23):4009.Google Scholar
  116. 116.
    Reddy SP, Rao N, Zammit D, Thompson SK, Smith RA, Denis L. A novel dual SYK/JAK inhibitor with strong antitumor activity in both hematological and solid tumor xenograft models [abstract]. Cancer Res. 2017;77(13 Suppl):4204.CrossRefGoogle Scholar
  117. 117.
    Hang L, Blum AM, Kumar S, Urban JF, Mitreva M, Geary TG, et al. Downregulation of the Syk signaling pathway in intestinal dendritic cells is sufficient to induce dendritic cells that inhibit colitis. J Immunol. 2016;197(7):2948–57.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Bissonnette R, Maari C, Forman SB, Bhatia N, Lee M, Fowler J, et al. Efficacy and safety of oral ASN002, a novel JAK/SYK inhibitor, in patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled clinical study [abstract]. American Academy of Dermatology Annual Meeting; 16–20 Feb 2018; San Diego.Google Scholar
  119. 119.
    Guttman-Yassky E, Pavel AB, Song T, Kim HJ, Bissonnette R, Denis L, et al. ASN002, a dual oral inhibitor of JAK/SYK signaling, improves the lesional skin phenotype towards non-involved skin in moderate-to-severe atopic dermatitis patients, correlating with clinical outcomes [abstract]. European Academy of Dermatology and Venereology. 12–16 Sep 2018; Paris.Google Scholar
  120. 120.
    Guttman-Yassky E, Pavel AB, Song T, Kim HJ, Zammit D, Toker S, et al. ASN002 a dual oral inhibitor of JAK/SYK signaling improves clinical outcomes and associated cutaneous inflammation in moderate-to-severe atopic dermatitis patients. J Investig Dermatol. 2018;138(5):S184.Google Scholar
  121. 121.
    PhRMA. Medicines in development for skin diseases: 2018 update. PhRMA; 2018 Sep 24. Accessed 27 Nov 2018.
  122. 122.
    McHale K, Harrington W, Roeloffs R, Lee J. Effect of RVT-502 therapy in the NC/Nga mouse model of atopic dermatitis. J Investig Dermatol. 2018;138(5):S184.CrossRefGoogle Scholar
  123. 123.
    Hasselbalch HC, Bjorn ME. Ruxolitinib versus standard therapy for the treatment of polycythemia vera [letter]. N Engl J Med. 2015;372(17):1670.CrossRefPubMedGoogle Scholar
  124. 124.
    Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rumi E, Gattoni E, et al. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017;130(15):1768–71.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    McKeage K. Ruxolitinib: a review in polycythaemia vera. Drugs. 2015;75(15):1773–81.CrossRefPubMedGoogle Scholar
  126. 126.
    Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363(12):1117–27.CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Plosker GL. Ruxolitinib: a review of its use in patients with myelofibrosis. Drugs. 2015;75(3):297–308.CrossRefPubMedGoogle Scholar
  129. 129.
    Joshipura D, Alomran A, Zancanaro P, Rosmarin D. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: a 32-week open-label extension study with optional narrow-band ultraviolet B. J Am Acad Dermatol. 2018;78(6):1205–7.CrossRefPubMedGoogle Scholar
  130. 130.
    Bayart CB, DeNiro KL, Brichta L, Craiglow BG, Sidbury R. Topical Janus kinase inhibitors for the treatment of pediatric alopecia areata. J Am Acad Dermatol. 2017;77(1):167–70.CrossRefPubMedGoogle Scholar
  131. 131.
    Craiglow BG, Tavares D, King BA. Topical ruxolitinib for the treatment of alopecia universalis. JAMA Dermatol. 2016;152(4):490–1.CrossRefPubMedGoogle Scholar
  132. 132.
    Deeb M, Beach RA. A case of topical ruxolitinib treatment failure in alopecia areata. J Cutan Med Surg. 2017;21(6):562–3.CrossRefPubMedGoogle Scholar
  133. 133.
    Corporation I. Incyte announces positive data from phase 2b trial of ruxolitinib cream in patients with atopic dermatitis [press release]. 2018 Sep 13. Accessed 3 Oct 2018.
  134. 134.
    Kim BS, Nasir A, Papp K, Parish LC, Kuligowski ME, Venturanza M, et al. A phase 2, randomized, dose-ranging, vehicle and active-controlled study to evaluate the safety and efficacy of ruxolitinib cream in adult patients with atopic dermatitis [abstract]. European Academy of Dermatology and Venereology. 12–16 Sep 2018; Paris.Google Scholar
  135. 135.
    Tanimoto A, Shinozaki Y, Yamamoto Y, Katsuda Y, Taniai-Riya E, Toyoda K, et al. A novel JAK inhibitor JTE-052 reduces skin inflammation and ameliorates chronic dermatitis in rodent models: comparison with conventional therapeutic agents. Exp Dermatol. 2018;27(1):22–9.CrossRefPubMedGoogle Scholar
  136. 136.
    Amano W, Nakajima S, Kunugi H, Numata Y, Kitoh A, Egawa G, et al. The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. J Allergy Clin Immunol. 2015;136(3):667–77.CrossRefPubMedGoogle Scholar
  137. 137.
    Nomura T, Kabashima K. Advances in atopic dermatitis in 2015. J Allergy Clin Immunol. 2016;138(6):1548–55.CrossRefPubMedGoogle Scholar
  138. 138.
    Nakagawa H, Nemoto O, Yamada H, Nagata T, Ninomiya N. Phase 1 studies to assess the safety, tolerability and pharmacokinetics of JTE-052 (a novel Janus kinase inhibitor) ointment in Japanese healthy volunteers and patients with atopic dermatitis. J Dermatol. 2018;45(6):701–9.CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Nakagawa H, Nemoto O, Igarashi A, Nagata T. Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: a phase II, multicentre, randomized, vehicle-controlled clinical study. Br J Dermatol. 2018;178(2):424–32.CrossRefPubMedGoogle Scholar
  140. 140.
    Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117(2):411–7.CrossRefPubMedGoogle Scholar
  141. 141.
    Sienna. Sienna Biopharmaceuticals announces results from first-in-human study of SNA-125 in psoriasis and continued progression to phase 2 [press release]. 2018 Aug 27. Accessed 3 Oct 2018.
  142. 142.
    Roblin D, Yosipovitch G, Boyce B, Robinson J, Sandy J, Mainero V, et al. Topical TrkA kinase inhibitor CT327 is an effective, novel therapy for the treatment of pruritus due to psoriasis: results from experimental studies, and efficacy and safety of CT327 in a phase 2b clinical trial in patients with psoriasis. Acta Derm Venereol. 2015;95(5):542–8.CrossRefPubMedGoogle Scholar
  143. 143.
    Bertarione L, Lizzul PF, Traversa S. SNA-125, a novel selective kinase inhibitor, improves clinical symptoms in a mouse model of psoriasis [abstract]. J Invest Dermatol. 2018;138(9):B18.CrossRefGoogle Scholar
  144. 144.
    van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, Garcia Meijide JA, Wagner S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508–19.CrossRefPubMedGoogle Scholar
  145. 145.
    Winthrop KL, Yamanaka H, Valdez H, Mortensen E, Chew R, Krishnaswami S, et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014;66(10):2675–84.CrossRefPubMedPubMedCentralGoogle Scholar
  146. 146.
    Strand V, Ahadieh S, French J, Geier J, Krishnaswami S, Menon S, et al. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther. 2015;17:362.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Furumoto Y, Gadina M. The arrival of JAK inhibitors: advancing the treatment of immune and hematologic disorders. BioDrugs. 2013;27(5):431–8.CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Chen Y, Gong F-Y, Li Z-J, Gong Z, Zhou Z, Ma S-Y, et al. A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis. Sci Rep. 2017;7(1):6779.CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Winthrop KL, Park S, Gul A, Cardiel MH, Gomez-Reino JJ, Tanaka Y, et al. Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(6):1133–8.CrossRefPubMedGoogle Scholar
  150. 150.
    Kuriya B, Cohen MD, Keystone E. Baricitinib in rheumatoid arthritis: evidence-to-date and clinical potential. Ther Adv Musculoskelet Dis. 2017;9(2):37–44.CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Maneiro JR, Souto A, Gomez-Reino JJ. Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: Systematic review, meta-analysis, and network meta-analysis. Semin Arthritis Rheum. 2017;47(2):149–56.CrossRefPubMedGoogle Scholar
  152. 152.
    Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016;75(5):831–41.CrossRefPubMedGoogle Scholar
  153. 153.
    Tanaka Y, Ishii T, Cai Z, Schlichting D, Rooney T, Macias W. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: a 52-week, randomized, single-blind, extension study. Mod Rheumatol. 2018;28(1):20–9.CrossRefPubMedGoogle Scholar
  154. 154.
    Sandborn WJ, Ghosh S, Panes J, Vranic I, Su C, Rousell S, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367(7):616–24.CrossRefPubMedGoogle Scholar
  155. 155.
    Xu D, Yin C, Wang S, Xiao Y. JAK-STAT in lipid metabolism of adipocytes. JAKSTAT. 2013;2(4):e27203.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Charles-Schoeman C, Wicker P, Gonzalez-Gay MA, Boy M, Zuckerman A, Soma K, et al. Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor. Semin Arthritis Rheum. 2016;46(3):261–71.CrossRefPubMedGoogle Scholar
  157. 157.
    Ostojic A, Vrhovac R, Verstovsek S. Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011;7(9):1035–43.CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc. 2011;86(12):1188–91.CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Pardanani A, Tefferi A. Definition and management of ruxolitinib treatment failure in myelofibrosis. Blood Cancer J. 2014;4(12):e268.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Dermatology and the Immunology InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Laboratory for Investigative DermatologyThe Rockefeller UniversityNew YorkUSA

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