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

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected.

The Role of Interleukin 23/17 Axis in Psoriasis Management: A Comprehensive Review of Clinical Trials.

Psoriasis pathogenesis is influenced by genetic factors and characterized by a complex interplay between genetic predisposition and various environmental triggers. These triggers set off metabolic processes involving inflammation, cell signaling, immune response dysregulation, and antigen presentation. Several types of innate and adaptive immune cells are involved in psoriasis. Among the cytokine cascade which leads to psoriasis development, the interleukin (IL)-23/Th17 axis, especially IL-17 production, emerges as crucial. Recognizing the pivotal role of this axis has facilitated the development of selective and effective biological drugs, such as anti-IL17 and anti-IL23 monoclonal antibodies. These drugs aim to achieve the complete or near-complete disappearance of psoriatic lesions, as indicated by PASI100 and PASI90 responses, respectively. In this context, the aim of our review was to delve into the functioning of the IL-23/Th17 axis, its dysregulation in psoriasis pathogenesis, and the therapeutic potential of its inhibition. Currently, 4 anti-IL17 (secukinumab, ixekizumab, bimekizumab and brodalumab) and 3 anti-IL23 (guselkumab, risankizumab and tildrakizumab) have been approved. All these drugs showed high levels of effectiveness in both clinical trials and real-life experiences, with an excellent profile in terms of safety. Certainly, furthers studies will allow for better characterization of biologics' profile, in order to administer the right drug for the right patients at the right moment.

An overview of new and emerging antibody therapies for moderate-severe atopic dermatitis in adults.

INTRODUCTION: A comprehensive review of the English-language medical literature was performed searching for ongoing and closed clinical trials concerning new and emerging monoclonal antibody therapies for moderate-to-severe atopic dermatitis in adults. AREAS COVERED: Atopic dermatitis is a chronic inflammatory cutaneous disease with a complex pathogenesis. In the last years, numerous advances in understanding the atopic dermatitis pathogenesis allowed to obtain several therapeutic options, such as numerous monoclonal antibodies. Some monoclonal antibodies, such as dupilumab (anti-IL-4 Rα) and tralokinumab (anti-IL13) are already approved for the treatment of moderate-to-severe atopic dermatitis, and numerous articles in the literature have demonstrated their efficacy and safety. As there are numerous drugs under investigation, this review focuses on emerging monoclonal antibody therapies. EXPERT OPINION: There are numerous monoclonal antibodies under investigation that may be approved in the near future for the treatment of atopic dermatitis. Data from phase 2b and phase III clinical trials in moderate-to-severe atopic dermatitis in adults indicate that these drugs have a promising efficacy and safety profile. Monoclonal antibodies currently under investigation will be available in the coming years to enrich the therapeutic choice of new alternatives that are valid both in terms of efficacy and safety.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.