Effectiveness of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis Located in Difficult-to-Treat Areas

Abstract

Background Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient’s quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers. Methods An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment. Results Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52. Conclusion Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.

JAK Inhibitors in Psoriatic Disease

“…In particular, the IL-23/Th17 axis is believed to play a central role. 26,27 Indeed, IL-23 drives the differentiation and proliferation of Th17 cells, which produce high levels of IL-17 and IL-22, causing keratinocyte proliferation and other typical features of psoriasis. 1 The JAK/STAT pathway family is composed of four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and Tyk2), and seven signal transductors (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT 5b, and STAT6) regulating signaling effects of multiple cytokines and growth factor on involved cells.…”

“…In particular, the IL-23/Th17 axis is believed to play a central role. 26 , 27 Indeed, IL-23 drives the differentiation and proliferation of Th17 cells, which produce high levels of IL-17 and IL-22, causing keratinocyte proliferation and other typical features of psoriasis. 1 …”

Long-Term Efficacy and Safety of Guselkumab in Psoriasis Patients Who Failed Anti-IL17: A Two-Year Real-Life Study

“…Moreover, the secondary outcome of our study was to investigate the effectiveness of guselkumab use following anti-IL17 failure in the so-called "difficult-to-treat areas" (scalp, genitals, palms and soles, fingernails). These areas are usually characterized by treatment resistance to conventional topical and systemic treatments, as well as a strong impact on patients' quality of life [14].…”