Authors Review Emerging Therapeutic Targets for Hidradenitis Suppurativa

Despite its impact on patient quality of life, hidradenitis suppurativa (HS) remains underdiagnosed and undertreated. Amid the challenges of managing HS, current treatment options offer only limited relief, underscoring the urgent need for innovative approaches, according to an article published in British Journal of Dermatology. Although systemic therapies and surgical interventions provide some respite, their efficacy varies, leaving many patients struggling to find effective relief.

Hidradenitis suppurativa diagnosis

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With mixed response rates, the approval of adalimumab indicates biologic options for HS are lacking, the authors noted. However, they also pointed to the rapidly evolving landscape of HS research and its diverse array of novel therapeutic agents under exploration in clinical trials. Promising targets, particularly those focusing on the interleukin (IL)-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, offer hope for improved outcomes.

However, significant hurdles persist, including diagnostic delays and a lack of standardized outcome measures, underscoring the imperative for ongoing advancements in the field to meet the unmet needs of those grappling with the chronic inflammatory condition. The journal article reviewed the evolving landscape of HS's pathophysiology and therapeutic interventions.

HS Pathophysiology Explained

Current understanding of HS pathophysiology is primarily based on histological and genetic profiling of skin biopsies. Although the tumor necrosis factor (TNF)-α and CD4+ helper T-cell pathways play crucial roles in HS, multiple other pathways and interactions contribute to its pathogenesis. Inflammation in early HS involves follicular hyperkeratosis, leading to the formation of comedones and folliculitis. Advanced stages of HS are characterized by inflammatory nodules, abscesses, and the formation of dermal tunnels, leading to tissue destruction and scarring.

Linking Pathophysiology With Treatment

Therapeutic interventions in HS target key pathways implicated in its pathogenesis, the article explained. Adalimumab, an anti–TNF-α antibody, has demonstrated efficacy in clinical trials, indicating the importance of TNF-α in HS inflammation. However, the authors noted that a significant proportion of patients do not respond adequately to adalimumab, suggesting the involvement of alternative pathways.

Research into IL-17 signaling has shown promise, with inhibitors like secukinumab demonstrating clinical efficacy. The IL-17 pathway, along with other cytokines such as IL-1β, is the main driver of inflammation and tissue destruction in HS lesions. Targeting these pathways presents new avenues for therapeutic intervention.

Emerging Therapeutic Targets

Research is underway to explore novel targets beyond TNF-α and IL-17. The article stated JAK/STAT pathways have garnered attention, with inhibitors like povorcitinib showing promising results in clinical trials. Additionally, other signal transduction targets such as IRAK4 and p38α MAPK/MK2 are under investigation.

Challenges and Unmet Needs

Despite advancements, the authors acknowledged existing challenges in HS management. Diagnostic delays are common, leading to missed treatment opportunities and disease progression, and a lack of standardized outcome measures in clinical trials hinders the evaluation of treatment efficacy. The heterogeneity of HS phenotypes further complicates disease characterization and treatment selection.

Ongoing Efforts

Research efforts are focusing on understanding the genetic basis of HS, identifying biomarkers for early diagnosis and predicting treatment response, and refining disease phenotypes. Collaborative initiatives are underway to develop standardized outcome measures and improve clinical trial design.

In conclusion, despite advancements in understanding and treatment, HS presents ongoing challenges, from diagnostic delays to limited therapeutic options. While the approval of adalimumab highlights the need for more effective biologics, ongoing research into novel targets like the IL-17 and JAK/STAT pathways provides potential for improved outcomes. Collaborative efforts are crucial to address these challenges and enhance the quality of life for individuals with HS.

Reference

Krueger JG, Frew J, Jemec GBE, et al. Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape. Br J Dermatol. 2024;190(2):149-162. doi:10.1093/bjd/ljad345