Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis

New England Journal of Medicine

Volumn 379, Issue 14, 2018, Pages 1313-1321

  Papp, Kim ^a   Gordon, Kenneth ^d   Thaçi, Diamant ^e   Morita, Akimichi ^f   Gooderham, Melinda ^b,c   Foley, Peter ^g   Girgis, Ihab G ^h   Kundu, Sudeep ^h   Banerjee, Subhashis ^h  

^a K Papp Clinical Research and Probity Medical Research   (Canada)

^b SKiN Centre for Dermatology and Probity Medical Research Inc   (Canada)

^c QUEEN S UNIVERSITY   (Canada)

^d MEDICAL COLLEGE OF WISCONSIN   (United States)

^e UNIVERSITY OF LÜBECK   (Germany)

^f NAGOYA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICAL SCIENCES   (Japan)

^g UNIVERSITY OF MELBOURNE   (Australia)

^h BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL PRODUCT; BMS 986165; CREATINE KINASE; FOCAL ADHESION KINASE INHIBITOR; PLACEBO; UNCLASSIFIED DRUG; JANUS KINASE INHIBITOR; PROTEIN KINASE TYK2;

ACNE; ADULT; APHTHOUS STOMATITIS; ARTICLE; ASYMPTOMATIC DISEASE; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DIARRHEA; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DOUBLE BLIND PROCEDURE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; EYE INJURY; FEMALE; GASTROENTERITIS; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; MELANOMA; MORNING DOSAGE; MULTICENTER STUDY; NAUSEA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; PSORIASIS; PSORIASIS AREA AND SEVERITY INDEX; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SIDE EFFECT; TOOTH PAIN; UPPER RESPIRATORY TRACT INFECTION; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; COMPARATIVE STUDY; DOSE RESPONSE; DRUG ADMINISTRATION; MIDDLE AGED; ORAL DRUG ADMINISTRATION; SEVERITY OF ILLNESS INDEX;

ADMINISTRATION, ORAL; ADULT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; JANUS KINASE INHIBITORS; MALE; MIDDLE AGED; PSORIASIS; SEVERITY OF ILLNESS INDEX; TYK2 KINASE;

EID: 85054421910     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1806382     Document Type: Article

References (36)

1. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol 2016; 38: 11-27.
2. Armstrong AW, Schupp C, Wu J, Bebo B. Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011. PLoS One 2012; 7(12): e52935.
3. Dubertret L, Mrowietz U, Ranki A, et al. European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey. Br J Dermatol 2006; 155: 729-36.
4. Helmick CG, Lee-Han H, Hirsch SC, Baird TL, Bartlett CL. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med 2014; 47: 37-45.
5. Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2017; 12: CD011535.
6. Drugs.com. Rheumatrex prescribing information. 2016 (https://www .drugs .com/ pro/ rheumatrex .html).
7. Novartis. Neoral prescribing information. 2009 (https://www .accessdata .fda .gov/ drugsatfda-docs/ label/ 2009/ 050715s027, 050716s028lbl .pdf).
8. Celgene. Otezla prescribing information. 2017 (http://media .celgene .com/ content/ uploads/ otezla -pi .pdf).
9. Novartis. Cosentyx prescribing information. 2018 (https://www .pharma .us .novartis .com/ sites/ www .pharma .us .novartis .com/ files/ cosentyx .pdf).
10. Eli Lilly. Taltz prescribing information. 2018 (http://pi .lilly .com/ us/ taltz -uspi .pdf).
11. Valeant Pharmaceuticals North America. Siliq prescribing information. 2017 (http://www .valeant .com/ Portals/ 25/ Pdf/ PI/ Siliq -pi .pdf).
12. AbbVie. Humira prescribing information. 2017 (http://www .rxabbvie .com/ pdf/ humira .pdf).
13. Janssen. Remicade prescribing information. 2017. (https://www .janssenmd .com/ pdf/ remicade/ remicade-pi .pdf).
14. Pfizer. Xeljanz prescribing information. 2017 (http://labeling .pfizer .com/ ShowLabeling .aspx?id=959).
15. Eli Lilly. Olumiant prescribing information. 2018 (http://pi .lilly .com/ us/ olumiant -uspi .pdf).
16. Shaw MH, Boyartchuk V, Wong S, et al. A natural mutation in the Tyk2 pseudokinase domain underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. Proc Natl Acad Sci U S A 2003; 100: 11594-9.
17. Lazear HM, Nice TJ, Diamond MS. Interferon-λ: immune functions at barrier surfaces and beyond. Immunity 2015; 43: 15-28.
18. Harden JL, Krueger JG, Bowcock AM. The immunogenetics of psoriasis: a comprehensive review. J Autoimmun 2015; 64: 66-73.
19. Yao Y, Richman L, Morehouse C, et al. Type I interferon: potential therapeutic target for psoriasis? PLoS One 2008; 3(7): e2737.
20. Majoros A, Platanitis E, Kernbauer- Hölzl E, Rosebrock F, Müller M, Decker T. Canonical and non-canonical aspects of JAK-STAT signaling: lessons from interferons for cytokine responses. Front Immunol 2017; 8: 29.
21. Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol 2007; 178: 2623-9.
22. Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine kinase 2-mediated signal transduction in T lymphocytes is blocked by pharmacological stabilization of its pseudokinase domain. J Biol Chem 2015; 290: 11061-74.
23. Gillooly K, Zhang Y, Yang X, et al. BMS-986165 is a highly potent and selective allosteric inhibitor of Tyk2, blocks IL- 12, IL-23 and type I interferon signaling and provides for robust efficacy in preclinical models of systemic lupus erythematosus and inflammatory bowel disease. Arthritis Rheumatol 2016; 68: Suppl 10: 11L. abstract.
24. Catlett I, Aras U, Liu Y, et al. A firstin- human study of BMS-986165, a selective, potent, allosteric small molecule inhibitor of tyrosine kinase 2. Ann Rheum Dis 2017; 76: Suppl 2: 859. abstract.
25. Thomas CL, Finlay AY. The 'handprint' approximates to 1% of the total body surface area whereas the 'palm minus the fingers' does not. Br J Dermatol 2007; 157: 1080-1.
26. Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new retinoid. Dermatologica 1978; 157: 238-44.
27. Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis 2005; 64: Suppl 2: ii65-ii73.
28. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210-6.
29. Tucci M, Lombardi L, Richards HB, Dammacco F, Silvestris F. Overexpression of interleukin-12 and T helper 1 predominance in lupus nephritis. Clin Exp Immunol 2008; 154: 247-54.
30. Dendrou CA, Cortes A, Shipman L, et al. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med 2016; 8: 363ra149.
31. Jani M, Massey J, Wedderburn LR, et al. Genotyping of immune-related genetic variants identifies TYK2 as a novel associated locus for idiopathic inflammatory myopathies. Ann Rheum Dis 2014; 73: 1750-2.
32. Dogra S, Jain A, Kanwar AJ. Efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized, double blind, parallel group, dose ranging study. J Eur Acad Dermatol Venereol 2013; 27(3): e305-e311.
33. Saurat JH, Stingl G, Dubertret L, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008; 158: 558-66.
34. Ho VC, Griffiths CE, Albrecht G, et al. Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study. Br J Dermatol 1999; 141: 283-91.
35. Papp KA, Menter A, Strober B, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a phase 2b randomized placebocontrolled dose-ranging study. Br J Dermatol 2012; 167: 668-77.
36. Janssen. Stelara prescribing information. 2017 (https://www .janssenmd .com/ pdf/ stelara/ stelara-pi .pdf).