Comparison of the Clinical Efficacy and Safety of Topical and Subcutaneous Injection of Secukinumab in HS

Официальное название

Comparison of the Efficacy and Safety of Topical and Subcutaneous Injection of Secukinumab in HS: A Prospective Exploratory Trial

Обзор

Secukinumab is currently approved in Europe, US and China for the treatment of moderate to severe HS as a biologic agent targeting IL-17A.Two phase III clinical trials (SUNSHINE and SUNRISE) showed that 300 mg s.c. every 2 weeks resulted in 42% to 45% of patients achieving a clinical response (HiSCR) to HS, and the efficacy was sustained through 52 weeks.However, we found in clinical practice that some HS patients present with localized lesions (small areas of involvement, affecting only 1-2 anatomic areas) that are resistant to conventional therapy, and have not yet fulfilled surgical indications, and the need for systemic biologic therapy is controversial.Such patients often experience inadequate response or slow onset of action when they receive secukinumab by routine subcutaneous injection - possibly related to inadequate drug concentration in the focal lesional area and limited local anti-inflammatory effects after systemic administration.In addition, side effects of conventional subcutaneous injection system are greater, and the application is limited in some patients, so it is necessary to explore more appropriate and safer drug delivery method for localized skin lesions.Localized HS, local injection of lesions may enhance anti-inflammatory effects while reducing systemic exposure by increasing drug concentrations at the lesion site.Therefore, exploring novel modes of administration of secukinumab has practical clinical implications based on clinical practice needs and the context of the previous literature.In summary, by exploring the efficacy and safety of local skin injection of secukinumab, this study may provide a new strategy for the treatment of limited HS with sufficient scientific rationale and significant potential benefits and manageable risks.

Подробное описание

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses, sinus tracts, and scarring, with a global prevalence of about 1%, occurring in apocrine gland-rich areas such as the axillae and groin. Its pathogenesis is closely related to hair follicle obstruction, dysbacteriosis and immune disorders, in which IL-17A-mediated inflammatory pathways have been demonstrated to be the core driver - IL-17A levels are significantly increased in HS lesions, which can promote neutrophil infiltration and abscess formation.

Secukinumab is currently approved in Europe, US and China for the treatment of moderate to severe HS as a biologic agent targeting IL-17A.Two phase III clinical trials (SUNSHINE and SUNRISE) showed that 300 mg s.c. every 2 weeks resulted in 42% to 45% of patients achieving a clinical response (HiSCR) to HS, and the efficacy was sustained through 52 weeks.However, we found in clinical practice that some HS patients present with localized lesions (small areas of involvement, affecting only 1-2 anatomic areas) that are resistant to conventional therapy, and have not yet fulfilled surgical indications, and the need for systemic biologic therapy is controversial.Such patients often experience inadequate response or slow onset of action when they receive secukinumab by routine subcutaneous injection - possibly related to inadequate drug concentration in the focal lesional area and limited local anti-inflammatory effects after systemic administration.In addition, side effects of conventional subcutaneous injection system are greater, and the application is limited in some patients, so it is necessary to explore more appropriate and safer drug delivery method for localized skin lesions.The successful experience of topical injection of biologics in psoriasis provides an important reference for clinical practice, such as study of nail psoriasis showed that intralesional secukinumab significantly increased local drug concentrations with 73.2% improvement in nail lesions and good safety.This suggests that for localized HS, local injection of lesions may enhance anti-inflammatory effects while reducing systemic exposure by increasing drug concentrations at the lesion site.Therefore, exploring novel modes of administration of secukinumab has practical clinical implications based on clinical practice needs and the context of the previous literature.In summary, by exploring the efficacy and safety of local skin injection of secukinumab, this study may provide a new strategy for the treatment of limited HS with sufficient scientific rationale and significant potential benefits and manageable risks.

Вмешательства

• Другое Topical injection of Secukinmab
  Topical injection of Secukinmab
• Препарат Subcutaneous injection of Secukinumab
  Subcutaneous injection of Secukinumab

Первичные конечные точки

• Change from Baseline in International HS Severity Score System (IHS4) [Срок оценки: Baseline (Day 1) and Week 24]

Вторичные конечные точки (7)

• Proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR)50 [Срок оценки: At Week4、8、12、16、20、24]
• Change from baseline in pain measured by Visual analog scale (VAS) [Срок оценки: Baseline (Day 1) and week4、8、12、16、20、24]
• Change from baseline in Dermatology Life Quality Index (DLQI) Total Score [Срок оценки: Baseline (Day 1) and week4、8、12、16、20、24]
• Change from baseline in white blood cell count (WBC) [Срок оценки: Baseline (Day 1) and week4、8、12、16、20、24]
• Change from baseline in serum level of high-density C-reactive protein (hs-CRP) [Срок оценки: Baseline (Day 1) and week4、8、12、16、20、24]
• Change from baseline in erythrocyte sedimentation rate (ESR) [Срок оценки: Baseline (Day 1) and week4、8、12、16、20、24]
• Change from baseline in serum level of Interleukin-6 (IL-6) [Срок оценки: Baseline (Day 1) and week4、8、12、16、20、24]

Критерии участия

Критерии включения

• Meet international diagnostic criteria for hidradenitis suppurativa
• Aged ≥ 18 years
• Disease duration ≥ 6 months and resistance to conventional therapy (no significant improvement for ≥ 3 months)
• Lesions were confined to a single anatomical area
• Voluntarily signed the informed consent form and was able to cooperate in all visits and examinations.

Критерии исключения

• Hypersensitivity to any component of secukinumab injection
• With severe vital organ failure
• With active infection or malignancy (malignancy within the past 5 years, except for basal or squamous cell carcinoma of the skin and cured)
• Treatment with biologics, immunosuppressants, or systemic corticosteroids within the last 3 months
• Pregnant, nursing, or planning conception during the study
• Mental disorders or cognitive impairment that precludes understanding of study procedures
• Participating in another clinical study and are at risk of an interaction between the study drugs
• Other conditions assessed by the investigators as inappropriate for participation in the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Science a — Нанкин

Публикации

• Griffin N, Williams AB, Anderson S, Irving PM, Sanderson J, Desai N, Goh V. Hidradenitis suppurativa: MRI features in anogenital disease. Dis Colon Rectum. 2014 Jun;57(6):762-71. doi: 10.1097/DCR.0000000000000131. PMID 24807602
• Nguyen TV, Damiani G, Orenstein LAV, Hamzavi I, Jemec GB. Hidradenitis suppurativa: an update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life. J Eur Acad Dermatol Venereol. 2021 Jan;35(1):50-61. doi: 10.1111/jdv.16677. Epub 2020 Jul 16. PMID 32460374
• Zouboulis CC, Desai N, Emtestam L, Hunger RE, Ioannides D, Juhasz I, Lapins J, Matusiak L, Prens EP, Revuz J, Schneider-Burrus S, Szepietowski JC, van der Zee HH, Jemec GB. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015 Apr;29(4):619-44. doi: 10.1111/jdv.12966. Epub 2015 Jan 30. PMID 25640693
• Zouboulis CC, Bechara FG, Fritz K, Goebeler M, Hetzer FH, Just E, Kirsten N, Kokolakis G, Kurzen H, Nikolakis G, Pinter A, Podda M, Rosinski K, Schneider-Burrus S, Taube KM, Volz T, Winkler T, Kristandt A, Presser D, Zouboulis VA. S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version. J Dtsch Dermatol Ges. 2024 Jun;22(6):868-889. doi: 10.1111/ddg.15412. Epub 20 PMID 38770982
• Kimball AB, Jemec GBE, Alavi A, Reguiai Z, Gottlieb AB, Bechara FG, Paul C, Giamarellos Bourboulis EJ, Villani AP, Schwinn A, Rueff F, Pillay Ramaya L, Reich A, Lobo I, Sinclair R, Passeron T, Martorell A, Mendes-Bastos P, Kokolakis G, Becherel PA, Wozniak MB, Martinez AL, Wei X, Uhlmann L, Passera A, Keefe D, Martin R, Field C, Chen L, Vandemeulebroecke M, Ravichandran S, Muscianisi E. Secukinuma PMID 36746171
• Kimball AB, Kerdel F, Adams D, Mrowietz U, Gelfand JM, Gniadecki R, Prens EP, Schlessinger J, Zouboulis CC, van der Zee HH, Rosenfeld M, Mulani P, Gu Y, Paulson S, Okun M, Jemec GB. Adalimumab for the treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012 Dec 18;157(12):846-55. doi: 10.7326/0003-4819-157-12-201212180-00004. PMID 23247938
• He F, Long FY, Zhang ZQ, Xia RY, Lu Y, Yin ZQ. Intramatricial injection of anti-interleukin-17A antibody for six patients with nail psoriasis. Clin Exp Dermatol. 2022 Feb;47(2):432-433. doi: 10.1111/ced.14933. Epub 2021 Oct 5. No abstract available. PMID 34510518
• Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC, Armstrong AW, Kerdel F, Gold MH, Forman SB, Korman NJ, Giamarellos-Bourboulis EJ, Crowley JJ, Lynde C, Reguiai Z, Prens EP, Alwawi E, Mostafa NM, Pinsky B, Sundaram M, Gu Y, Carlson DM, Jemec GB. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016 Aug 4;375(5):422-34. doi: 10.1056/NEJMoa1504370. PMID 27518661

Идентификаторы

NCT: NCT07261072 · 2025-KY-067

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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