J L Blok1, K Li2, C Brodmerkel2, P Horvátovich3, M F Jonkman1, B Horváth1. 1. Department of Dermatology, University Medical Center Groningen, Groningen, the Netherlands. 2. Janssen Research and Development, LLC, Spring House, PA, U.S.A. 3. Department of Pharmacy, Analytical Biochemistry, Faculty of Mathematics and Natural Sciences, University of Groningen, Groningen, the Netherlands.
Abstract
BACKGROUND: Treatment of hidradenitis suppurativa (HS) is difficult and the search for effective therapies continues. OBJECTIVES: To evaluate the efficacy of ustekinumab and to discover a potential biomarker for HS. METHODS: Seventeen patients were included in this open-label study and treated with 45 or 90 mg ustekinumab at weeks 0, 4, 16 and 28. Proteomic technology and enzyme-linked assay analysis was applied to sera. RESULTS: Twelve patients completed the protocol. Moderate-to-marked improvement of the modified Sartorius score was achieved in 82% of patients at week 40 and the Hidradenitis Suppurativa Clinical Response 50 in 47%. With regard to the expression of 54 serum proteins, at baseline, a significant difference was observed between patients and healthy controls. Involved pathways were related to inflammation, immune cell signalling and tissue morphology/development. Good responders had milder disease and lower expression of leukotriene A4-hydrolase (LTA4H). Interleukin (IL)-2R, tumour necrosis factor-α, IL-17A and IL-17F were not elevated and did not change during treatment. CONCLUSIONS: The majority of patients improved with ustekinumab. Although no biomarker was discovered, low LTA4H concentrations with mild disease severity may be predictive of the effectiveness of ustekinumab.
BACKGROUND: Treatment of hidradenitis suppurativa (HS) is difficult and the search for effective therapies continues. OBJECTIVES: To evaluate the efficacy of ustekinumab and to discover a potential biomarker for HS. METHODS: Seventeen patients were included in this open-label study and treated with 45 or 90 mg ustekinumab at weeks 0, 4, 16 and 28. Proteomic technology and enzyme-linked assay analysis was applied to sera. RESULTS: Twelve patients completed the protocol. Moderate-to-marked improvement of the modified Sartorius score was achieved in 82% of patients at week 40 and the Hidradenitis Suppurativa Clinical Response 50 in 47%. With regard to the expression of 54 serum proteins, at baseline, a significant difference was observed between patients and healthy controls. Involved pathways were related to inflammation, immune cell signalling and tissue morphology/development. Good responders had milder disease and lower expression of leukotriene A4-hydrolase (LTA4H). Interleukin (IL)-2R, tumour necrosis factor-α, IL-17A and IL-17F were not elevated and did not change during treatment. CONCLUSIONS: The majority of patients improved with ustekinumab. Although no biomarker was discovered, low LTA4H concentrations with mild disease severity may be predictive of the effectiveness of ustekinumab.
Authors: Mariabeatrice Principi; Nicoletta Cassano; Antonella Contaldo; Andrea Iannone; Giuseppe Losurdo; Michele Barone; Mario Mastrolonardo; Gino Antonio Vena; Enzo Ierardi; Alfredo Di Leo Journal: World J Gastroenterol Date: 2016-05-28 Impact factor: 5.742
Authors: Eran Shavit; Afsaneh Alavi; Falk G Bechara; Richard G Bennett; Marc Bourcier; Ricardo Cibotti; Steven Daveluy; John W Frew; Amit Garg; Iltefat Hamzavi; Lauren K Hoffman; Jenny Hsaio; Joslyn Sciacca Kirby; Hadar Lev-Tov; Erin Martinez; Robert Micheletti; Haley B Naik; Aude Nassif; Cynthia Nicholson; Angie Parks-Miller; Zarine Patel; Vincent Piguet; Mayur Ramesh; Barry Resnik; Christopher Sayed; Gregory Schultz; Aamir Siddiqui; Jerry Tan; Ximena Wortsman; Michelle A Lowes Journal: Exp Dermatol Date: 2019-01 Impact factor: 3.960
Authors: Ali Alikhan; Christopher Sayed; Afsaneh Alavi; Raed Alhusayen; Alain Brassard; Craig Burkhart; Karen Crowell; Daniel B Eisen; Alice B Gottlieb; Iltefat Hamzavi; Paul G Hazen; Tara Jaleel; Alexa B Kimball; Joslyn Kirby; Michelle A Lowes; Robert Micheletti; Angela Miller; Haley B Naik; Dennis Orgill; Yves Poulin Journal: J Am Acad Dermatol Date: 2019-03-11 Impact factor: 15.487
Authors: Ali Alikhan; Christopher Sayed; Afsaneh Alavi; Raed Alhusayen; Alain Brassard; Craig Burkhart; Karen Crowell; Daniel B Eisen; Alice B Gottlieb; Iltefat Hamzavi; Paul G Hazen; Tara Jaleel; Alexa B Kimball; Joslyn Kirby; Michelle A Lowes; Robert Micheletti; Angela Miller; Haley B Naik; Dennis Orgill; Yves Poulin Journal: J Am Acad Dermatol Date: 2019-03-11 Impact factor: 15.487