Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis

Experimental Dermatology

Volumn 26, Issue 1, 2017, Pages 28-35

  Khattri, Saakshi ^a,b   Brunner, Patrick M ^a   Garcet, Sandra ^a   Finney, Robert ^c   Cohen, Steven R ^d   Oliva, Margeaux ^a,b   Dutt, Riana ^a,b   Fuentes Duculan, Judilyn ^a   Zheng, Xiuzhong ^a   Li, Xuan ^a   Bonifacio, Kathleen M ^a   Kunjravia, Norma ^a   Coats, Israel ^a   Cueto, Inna ^a   Gilleaudeau, Patricia ^a   Sullivan Whalen, Mary ^a   Suárez Fariñas, Mayte ^a,b   Krueger, James G ^a   Guttman Yassky, Emma ^a,b  

^a ROCKEFELLER UNIVERSITY   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

^d ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

atopic dermatitis; IL 12; IL 22; IL 23; p40; ustekinumab

Indexed keywords

CXCL1 CHEMOKINE; CYTOKINE; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 12P19; INTERLEUKIN 12P40; INTERLEUKIN 13; INTERLEUKIN 22; INTERLEUKIN 23P19; INTERLEUKIN 23P40; MACROPHAGE ELASTASE; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE; PLACEBO; THYMUS AND ACTIVATION REGULATED CHEMOKINE; TRIAMCINOLONE ACETONIDE; UNCLASSIFIED DRUG; USTEKINUMAB; CCL17 PROTEIN, HUMAN; CXCL1 PROTEIN, HUMAN; DERMATOLOGICAL AGENT; INTERLEUKIN DERIVATIVE; INTERLEUKIN-13, HUMAN; INTERLEUKIN-22; MMP12 PROTEIN, HUMAN; PI3 PROTEIN, HUMAN; TIPRELESTAT; TRANSCRIPTOME;

ABSENCE OF SIDE EFFECTS; ADULT; ARTICLE; ATOPIC DERMATITIS; CLINICAL ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; GENE EXPRESSION; GENE EXPRESSION PROFILING; HUMAN; MALE; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SKIN BIOPSY; TH1 CELL; TH17 CELL; TH2 CELL; TH22 CELL; TREATMENT RESPONSE; CLINICAL TRIAL; DRUG EFFECTS; GENETICS; PATHOLOGY; SEVERITY OF ILLNESS INDEX;

ADULT; CHEMOKINE CCL17; CHEMOKINE CXCL1; CROSS-OVER STUDIES; DERMATITIS, ATOPIC; DERMATOLOGIC AGENTS; DOUBLE-BLIND METHOD; ELAFIN; FEMALE; GENE EXPRESSION PROFILING; HUMANS; INTERFERON-GAMMA; INTERLEUKIN-13; INTERLEUKINS; MALE; MATRIX METALLOPROTEINASE 12; SEVERITY OF ILLNESS INDEX; TRANSCRIPTOME; USTEKINUMAB;

EID: 84982952552     PISSN: 09066705     EISSN: 16000625     Source Type: Journal    
DOI: 10.1111/exd.13112     Document Type: Article

References (44)

1. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, et al. Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. J Allergy Clin Immunol. 2007;119:1210–1217.
2. Nograles KE, Zaba LC, Shemer A, et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009;123:1244–1252.
3. Czarnowicki T, Krueger JG, Guttman-Yassky E. Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. J Allergy Clin Immunol Pract. 2014;2:371–379.
4. Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis—part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011;127:1420–1432.
5. Eyerich K, Novak N. Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013;68:974–982.
6. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015;33:13–23.
7. Noda S, Krueger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015;135:324–336.
8. Mansouri Y, Guttman-Yassky E. Immune pathways in atopic dermatitis, and definition of biomarkers through broad and targeted therapeutics. J Clin Med. 2015;4:858–873.
9. Suarez-Farinas M, Ungar B, Noda S, et al. Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing. J Allergy Clin Immunol. 2015;136:1277–1287.
10. Zaghi D, Krueger GG, Callis Duffin K. Ustekinumab: a review in the treatment of plaque psoriasis and psoriatic arthritis. J Drugs Dermatol. 2012;11:160–167.
11. Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol. 2014;32:227–255.
12. Reddy M, Torres G, McCormick T, et al. Positive treatment effects of ustekinumab in psoriasis: analysis of lesional and systemic parameters. J Dermatol. 2010;37:413–425.
13. Agusti-Mejias A, Messeguer F, Garcia R, Febrer I. Severe refractory atopic dermatitis in an adolescent patient successfully treated with ustekinumab. Ann Dermatol. 2013;25:368–370.
14. Puya R, Alvarez-Lopez M, Velez A, Casas Asuncion E, Moreno JC. Treatment of severe refractory adult atopic dermatitis with ustekinumab. Int J Dermatol. 2012;51:115–116.
15. Fernandez-Anton Martinez MC, Alfageme Roldan F, Ciudad Blanco C, Suarez Fernandez R. Ustekinumab in the treatment of severe atopic dermatitis: a preliminary report of our experience with 4 patients. Actas Dermosifiliogr. 2014;105:312–313.
16. Shroff A, Guttman-Yassky E. Successful use of ustekinumab therapy in refractory severe atopic dermatitis. JAAD Case Rep. 2015;1:25–26.
17. Samorano LP, Hanifin JM, Simpson EL, Leshem YA. Inadequate response to ustekinumab in atopic dermatitis—a report of two patients. J Eur Acad Dermatol Venereol. 2016;30:522–523.
18. Wlodek C, Hewitt H, Kennedy CT. Use of ustekinumab for severe refractory atopic dermatitis in a young teenager. Clin Exp Dermatol. 2016;41:625–627.
19. Brunner PM, Khattri S, Garcet S, et al. A mild topical steroid leads to progressive anti-inflammatory effects in the skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2016;138:169–178.
20. Tintle S, Shemer A, Suarez-Farinas M, et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol. 2011;128:583–593.
21. Suarez-Farinas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol. 2011;127:954–964.
22. Suarez-Farinas M, Pellegrino M, Wittkowski KM, Magnasco MO. Harshlight: a “corrective make-up” program for microarray chips. BMC Bioinformatics. 2005;6:294.
23. Wu Z, Irizarry R, Gentleman R, Martinez-Murillo F, Spencer F. A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc. 2004;99:909–917.
24. Hamilton JD, Suarez-Farinas M, Dhingra N, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014;134:1293–1300.
25. Suarez-Farinas M, Lowes MA, Zaba LC, Krueger JG. Evaluation of the psoriasis transcriptome across different studies by gene set enrichment analysis (GSEA). PLoS One. 2010;5:e10247.
26. Novak N, Leung DY. Advances in atopic dermatitis. Curr Opin Immunol. 2011;23:778–783.
27. Peng J, Yang XO, Chang SH, Yang J, Dong C. IL-23 signaling enhances Th2 polarization and regulates allergic airway inflammation. Cell Res. 2010;20:62–71.
28. Nakajima S, Kitoh A, Egawa G, et al. IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models. J Invest Dermatol. 2014;134:2122–2130.
29. + T cell lineage differentiation. Immunity. 2009;30:646–655.
30. Becattini S, Latorre D, Mele F, et al. T cell immunity. Functional heterogeneity of human memory CD4(+) T cell clones primed by pathogens or vaccines. Science. 2015;347:400–406.
31. Cao Z, Carter C, Wilson KL, Schenkel B. Ustekinumab dosing, persistence, and discontinuation patterns in patients with moderate-to-severe psoriasis. J Dermatolog Treat. 2015;26:113–120.
32. Czarnowicki T, Malajian D, Shemer A, et al. Skin-homing and systemic T-cell subsets show higher activation in atopic dermatitis versus psoriasis. J Allergy Clin Immunol. 2015;136:208–211.
33. Czarnowicki T, Gonzalez J, Shemer A, 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;136:104–115.
34. Beck LA, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–139.
35. Thaci D, Simpson EL, Beck LA, 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;387:40–52.
36. Noda S, Suarez-Farinas M, Ungar B, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased T17 polarization. J Allergy Clin Immunol. 2015;136:1254–1264.
37. Gittler JK, Shemer A, Suarez-Farinas M, 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;130:1344–1354.
38. Kabashima-Kubo R, Nakamura M, Sakabe J, et al. A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type. J Dermatol Sci. 2012;67:37–43.
39. Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387:1109–1122.
40. Toda M, Leung DY, Molet S, et al. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol. 2003;111:875–881.
41. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol. 2008;128:2625–2630.
42. Suarez-Farinas M, Dhingra N, Gittler J, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132:361–370.
43. Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134:769–779.
44. Czarnowicki T, Esaki H, Gonzalez J, 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;136:941–951.