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

Overview

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.

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.