John W Frew1, Kristina Navrazhina2, David Grand3, Mary Sullivan-Whalen1, Patricia Gilleaudeau1, Sandra Garcet1, Jonathan Ungar4, James G Krueger5. 1. Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York. 2. Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York; Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program, Weill Cornell Medicine, New York, New York. 3. Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York; Albert Einstein College of Medicine, Bronx, New York. 4. Icahn School of Medicine at Mount Sinai, New York, New York. 5. Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York. Electronic address: jgk@rockefeller.edu.
Abstract
BACKGROUND: Hidradenitis suppurativa is an autoinflammatory disorder of keratinization, with dysregulation of T helper type 17 cytokines. Brodalumab is a monoclonal antibody that targets the interleukin (IL) 17 receptor A receptor. OBJECTIVES: To assess the safety and tolerability and clinical response at weeks 12 and 24 of brodalumab in moderate to severe HS. Ten participants with no history of inflammatory bowel disease were administered brodalumab 210 mg/1.5 mL subcutaneously at weeks 0, 1, and 2 and every 2 weeks thereafter until week 24. Participants were assessed for adverse events (grade 2/3 adverse events) and clinical response (Hidradenitis Suppurativa Clinical Response [HiSCR], Sartorius, International Hidradenitis Suppurativa Severity Scoring System [IHS4]), including ultrasonography and skin biopsies. RESULTS: All 10 participants completed the study. No grade 2/3 adverse events associated with the use of brodalumab were reported. All patients (100%) achieved HiSCR, and 80% achieved IHS4 category change at week 12. HiSCR achievement occurred as early as week 2, likely due to the unique blockade of IL-17A, IL-17C, and IL-17F by brodalumab. Significant improvements were seen in pain, itch, quality of life, and depression. CONCLUSIONS: Brodalumab was well tolerated in this HS cohort, with no serious adverse events and improvement in clinical outcomes. Alterations in dose frequency may be required in those with advanced disease, which requires further exploration.
BACKGROUND:Hidradenitis suppurativa is an autoinflammatory disorder of keratinization, with dysregulation of T helper type 17 cytokines. Brodalumab is a monoclonal antibody that targets the interleukin (IL) 17 receptor A receptor. OBJECTIVES: To assess the safety and tolerability and clinical response at weeks 12 and 24 of brodalumab in moderate to severe HS. Ten participants with no history of inflammatory bowel disease were administered brodalumab 210 mg/1.5 mL subcutaneously at weeks 0, 1, and 2 and every 2 weeks thereafter until week 24. Participants were assessed for adverse events (grade 2/3 adverse events) and clinical response (Hidradenitis Suppurativa Clinical Response [HiSCR], Sartorius, International Hidradenitis Suppurativa Severity Scoring System [IHS4]), including ultrasonography and skin biopsies. RESULTS: All 10 participants completed the study. No grade 2/3 adverse events associated with the use of brodalumab were reported. All patients (100%) achieved HiSCR, and 80% achieved IHS4 category change at week 12. HiSCR achievement occurred as early as week 2, likely due to the unique blockade of IL-17A, IL-17C, and IL-17F by brodalumab. Significant improvements were seen in pain, itch, quality of life, and depression. CONCLUSIONS:Brodalumab was well tolerated in this HS cohort, with no serious adverse events and improvement in clinical outcomes. Alterations in dose frequency may be required in those with advanced disease, which requires further exploration.
Authors: C C Zouboulis; T Tzellos; A Kyrgidis; G B E Jemec; F G Bechara; E J Giamarellos-Bourboulis; J R Ingram; T Kanni; I Karagiannidis; A Martorell; Ł Matusiak; A Pinter; E P Prens; D Presser; S Schneider-Burrus; E von Stebut; J C Szepietowski; H H van der Zee; S M Wilden; R Sabat Journal: Br J Dermatol Date: 2017-10-30 Impact factor: 9.302
Authors: John W Frew; Caroline S Jiang; Neha Singh; David Grand; Kristina Navrazhina; Roger Vaughan; James G Krueger Journal: J Am Acad Dermatol Date: 2019-12-24 Impact factor: 11.527
Authors: Mark G Lebwohl; Kim A Papp; Lauren B Marangell; John Koo; Andrew Blauvelt; Melinda Gooderham; Jashin J Wu; Shipra Rastogi; Susan Harris; Radhakrishnan Pillai; Robert J Israel Journal: J Am Acad Dermatol Date: 2017-10-03 Impact factor: 11.527
Authors: J W Frew; K Navrazhina; A S Byrd; A Garg; J R Ingram; J S Kirby; M A Lowes; H Naik; V Piguet; E P Prens Journal: Br J Dermatol Date: 2019-08-29 Impact factor: 11.113
Authors: A B Kimball; J M Sobell; C C Zouboulis; Y Gu; D A Williams; M Sundaram; H D Teixeira; G B E Jemec Journal: J Eur Acad Dermatol Venereol Date: 2015-07-22 Impact factor: 6.166
Authors: Puneet Agarwal; Snehal Balvant Lunge; Nandini Sundar Shetty; Priyanka Karagaiah; Steven Daveluy; Alex G Ortega-Loayza; Thrasyvoulos Tzellos; Jacek C Szepietowski; Christos C Zouboulis; Stephan Grabbe; Mohamad Goldust Journal: J Clin Med Date: 2022-06-30 Impact factor: 4.964
Authors: Kristina Navrazhina; John W Frew; David Grand; Samuel C Williams; Hong Hur; Juana Gonzalez; Sandra Garcet; James G Krueger Journal: Br J Dermatol Date: 2022-06-02 Impact factor: 11.113
Authors: Kristina Navrazhina; John W Frew; Patricia Gilleaudeau; Mary Sullivan-Whalen; Sandra Garcet; James G Krueger Journal: J Allergy Clin Immunol Date: 2021-02-03 Impact factor: 14.290
Authors: Ester Del Duca; Paola Morelli; Luigi Bennardo; Cosimo Di Raimondo; Steven Paul Nisticò Journal: Int J Mol Sci Date: 2020-11-10 Impact factor: 5.923
Authors: Kristina Navrazhina; Sandra Garcet; John W Frew; Xiuzhong Zheng; Israel Coats; Emma Guttman-Yassky; James G Krueger Journal: J Am Acad Dermatol Date: 2021-07-30 Impact factor: 11.527
Authors: Pim Aarts; Koen Dudink; Allard R J V Vossen; Kelsey R van Straalen; Christine B Ardon; Errol P Prens; Hessel H van der Zee Journal: Drugs Date: 2021-07-20 Impact factor: 9.546