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Biological monoclonal antibody drugs inhibit overactive cytokine signalling that drives chronic inflammatory disease in different organ systems. In the last 10 years, interleukin (IL)-23 inhibitors have attained an important position in the treatment of psoriatic skin and joint disease as well as inflammatory bowel diseases. Addressing an upstream pathological mechanism shared between these disorders, this drug class has high efficacy rates and a durable response that extends dosing intervals up to 3 months. Pooled clinical trial data show objective disease improvement for more than 70% of patients with psoriasis and up to 50% of patients with inflammatory bowel disease. The first antibody inhibitor for IL-23A targeted a p40 subunit shared with IL-12. Subsequently, even greater improvement was established for inhibitors of the p19 protein unique to IL-23A. IL-23 p19 inhibitors elicit clinical response in both bio-naive and bio-exposed patients and show superiority to tumour necrosis factor α inhibitors in plaque psoriasis. Reported differences in efficacy between p19 inhibitors suggest that individual drug action might be modulated by antibody affinity. Although long-term safety data are accumulating, rates of serious adverse events and infections for interleukin (IL)-23 inhibitors are similar to the rates for placebo across approved indications., Competing Interests: Declaration of interests VJ received research funding from Celgene/BMS, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead Sciences, and Tigenix; and declares receiving compensation from AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, BioJamp, Celgene/BMS, Celltrion, Eli Lilly, Ferring, F. Hoffman-La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD Network, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Knightslab, Organon (Merck), Landos BioPharma, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist Therapeutics, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx Biosciences, Viatris, and Vividion Therapeutics. MLAF received research fundings from PANLAR, Novartis, and Janssen; and received compensation from Asoforma and Janssen. RJC received research funding from Sun Pharma, Leo Pharma, Bristol Myers Squibb, Regeneron, and Janssen., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Risankizumab is an interleukin 23p19 inhibitor, approved by the USA Food and Drug Administration (FDA) for the management of moderate to severe plaque psoriasis. Apart from its utility in psoriasis, there are a number of other dermatologic conditions where risankizumab has demonstrated value. The aim of this narrative review is to describe the utility of risankizumab in psoriasis, as well as its implication in off-label dermatologic disorders., Evidence Acquisition: PubMed, Google Scholar, Scopus and ResearchGate were searched for scholarly articles related to risankizumab and its utility in dermatology using the search terms "Risankizumab" AND "Psoriasis" AND "other dermatological disorders.", Evidence Synthesis: Risankizumab is a valuable biologic agent for the management of psoriasis and psoriatic arthropathy. It has also been used successfully for other dermatologic disorders like hidradenitis suppurativa, pityriasis rubra pilaris and pyoderma gangrenosum., Conclusions: Risankizumab's usage is not limited to psoriasis. Its benefit extends to many more dermatologic conditions. Besides, it has an acceptable safety profile.

Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors., Competing Interests: Disclosure J.M. Cohen serves on a data and safety monitoring board for Advarra. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To study the effects of the anti-IL-23A antibody risankizumab on the IL-36γ/IL-23A/IL-17A signalling cascade we used a newly developed 3D skin model consisting of primary human keratinocytes, fibroblasts and γδ-T-cells., Methods: In this in vitro study we developed new full-thickness 3D skin models containing normal human epidermal keratinocytes (NHEK), normal human dermal fibroblasts (NHDF) and IL-23A responsive and IL-17A producing γδ-T-cells. The effects of IL-36γ stimulation with and without risankizumab treatment on IL-23A and IL-17A expression were examined at the RNA and protein levels., Results: In preliminary monolayer experiments stimulation of γδ-T-cells with IL-23A promoted the IL-17A expression that was inhibited after risankizumab treatment. Using 3D skin models containing γδ-T-cells, we found that stimulation with IL-36γ significantly increased not only IL-23A but also IL-17A expression. These effects were inhibited by concomitant treatment with risankizumab., Conclusions: Our results showed that blockade of IL-23A has inhibitory effects on the IL-36γ/IL-23A feedforward loop. Our newly developed 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells enables molecular analysis of targeted therapies aimed at the IL-36γ/IL-23A/IL-17A signalling cascade in psoriasis.

The pathogenesis of psoriasis has been linked to autoimmune and autoinflammatory traits that result in atypical cytokine and keratinocyte activation and proliferation. Many cytokine pathways are involved in the development of inflammation with interleukin-23 (IL-23) playing a significant role in plaque-type psoriasis. Biologic agents that target specific cytokines have shown to be effective therapies in the treatment of plaque-type psoriasis over other conventional treatments such as systemic retinoids. Tildrakizumab is an immunoglobulin G1-kappa monoclonal antibody that inhibits the IL-23/IL-17 pathway and has demonstrated through two three-part randomized Phase 3 clinical trials (reSURFACE 1 and reSURFACE 2) and their extension trials to be an efficacious and safe therapy for the targeted treatment of moderate-to-severe plaque-type psoriasis., Competing Interests: The authors have no conflicts of interest to declare. Funding: None.

Background: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis., Objective: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications., Methods: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up., Results: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed., Limitations: The proper of the study designed and the arbitrary definition of "DR success.", Conclusion: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving., (© 2024 the International Society of Dermatology.)

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios., (Copyright © 2023. Published by Elsevier España, S.L.U.)

The management of psoriasis in individuals with human immunodeficiency virus (HIV) presents a unique challenge, marked by a more severe progression and limited efficacy of first- and second-line treatments. Although conventional systemic therapies might be considered, these agents are immunosuppressants, making their use challenging in people living with HIV (PLHIV). Biologic agents are frequently used in individuals with moderate-to-severe psoriasis, but their efficacy and safety data in PLHIV are very limited, as this patient group tends to be excluded from clinical trials. Risankizumab is a selective interleukin-23 (IL-23) inhibitor that has demonstrated a favourable safety profile and high efficacy in long-term studies and clinical practice. This current case report presents two clinical cases of PLHIV with plaque psoriasis who were effectively treated with the biologic agent risankizumab, with no reported safety issues. Although there are limited data on the use of biologics in PLHIV, this case series suggests that IL-23 inhibitors, namely risankizumab, might be a valuable therapeutic option for this population. Additional research and larger studies are needed to gain a more comprehensive understanding of the long-term safety and efficacy of IL-23 inhibitors in individuals affected by HIV., Competing Interests: Declaration of conflicting interestsT.E. and E.F. declare that there are no conflicts of interest. T.T. declares the following conflicts of interest: AbbVie, Amgen, Almirall, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, Biocad, LEO Pharma, Eli Lilly, MSD, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme and Sandoz.

Background: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production., Methods: In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16., Results: A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups., Conclusions: After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.)., (Copyright © 2024 Massachusetts Medical Society.)

Data on guselkumab as treatment for moderate-to-severe plaque psoriasis, especially in different body regions, in China is limited. This study aimed to estimate the effectiveness of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis, including effectiveness at different body regions. This multicentre, observational study retrospectively enrolled patients with moderate-to-severe plaque psoriasis. Effectiveness outcome was based on Psoriasis Area and Severity Index (PASI) response and improvement in Body Surface Area (BSA) and Dermatology Life Quality Index (DLQI). A total of 51 patients were included, with a median age of 44.00 (18.00, 74.00) years and median duration of psoriasis of 10.00 (0.50, 55.00) years. After 20 weeks of treatment, PASI response with 75% improvement from baseline (PASI 75) was reported in 96.1% of patients; 72.5% of patients achieved a DLQI score of 0-1 at week 20. The percentage of affected BSA was significantly decreased at week 4 (p<0.05), week 12 (p<0.001) and week 20 (p<0.001). PASI score significantly changed from baseline after four weeks (p<0.001), 12 weeks (p<0.001) and 20 weeks of treatment (p<0.001). DLQI score significantly increased at week 4 (p<0.001), week 12 (p<0.001) and week 20 (p<0.001). PASI 75 was achieved for the upper limbs in all cases and 100% PASI improvement (PASI 100) in 89.1%. The head and lower limbs were the areas least responsive to treatment, with PASI 100 achieved in only 68.6% and 70.6%, respectively. Guselkummab provided rapid and sustained PASI improvement, especially for the skin of the upper limbs and body trunk.

Generalized pustular psoriasis (GPP) is a severe and uncommon form of psoriasis, for which treatment options are limited. There is an urgent need to expand the treatment options for GPP. Currently, adalimumab, secukinumab, and guselkumab are considered effective for GPP, but there is a lack of prospective direct comparative studies on their efficacy for GPP. We conducted a prospective, single-center, observational study on 50 GPP patients to compare the efficacy, safety, and recurrence rates of these three biologics. Adalimumab, secukinumab, and guselkumab resulted in varying degrees of improvement in patients with GPP, but guselkumab exhibited superior efficacy and a lower recurrence rate than the other two drugs. This enhanced response may be attributed to the significant reduction in CD8+ tissue-resident memory T cells within GPP lesions caused by guselkumab., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Biologics targeting IL-23 and IL-17 show efficacy and safety in the treatment of moderate-to-severe psoriasis., Objective: To investigate drug survival in patients with psoriasis treated with biologics., Patients and Methods: We performed a comparative evaluation of the achievement of PASI 90 and PASI ≤ 3 at 16, 28, and 52 weeks along with a DS (drug survival) analysis with IL-17 and IL-23 inhibitors brodalumab, ixekizumab, secukinumab, risankizumab, tildrakizumab, and guselkumab on 1,057 patients., Results: IL-17 inhibitors showed a faster achievement of PASI 90 and PASI ≤ 3 with significant superiority over IL-23 inhibitors at week 16 (p < 0.001; 56% vs. 42% and 70% vs. 59%, respectively). A difference was shown in favor of IL-23 inhibitors regarding DS (p < 0.001), which was 88% at 24 months vs. 75% for IL-17 inhibitors. In multivariate analysis, IL-23 inhibitors (HR 0.54 CI 0.37-0.78, p = 0.001), and male sex (HR 0.57 CI 0.42-0.76, p < 0.001) were all associated with a lower probability of drug interruption. Risankizumab (HR 0.42 CI 0.26-0.69, p = 0.001), guselkumab (HR 0.49 CI 0.24-0.99, p = 0.046), and male sex (HR 0.57 CI 0.43-0.77, p < 0.001) were associated with a lower probability of drug interruption than secukinumab., Conclusions: IL-23 inhibitors showed the best performance on DS. Overall, the most effective class was IL-17 inhibitors considering the short-term effectiveness, but long-term effectiveness is in favor of anti-IL-23., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

The management of plaque psoriasis that affects difficult-to-treat areas can be challenging. Biologics have become the treatment of choice for moderate-to-severe plaque psoriasis. However, there are limited data on their efficacy in difficult-to-treat sites (including scalp, palms/soles, nails and genitalia). We conducted a 52-week retrospective study to evaluate the effectiveness of risankizumab in 202 patients with moderate-to-severe involvement of at least one difficult-to-treat area. One hundred and sixty-five patients had scalp psoriasis, 21 had involvement of palms or soles, 72 were affected by genital psoriasis, and 50 patients reported the involvement of the fingernails. After one year of treatment, 97.58% of patients with scalp involvement, 95.28% of patients with palmoplantar psoriasis, 100% of patients with genital psoriasis and 82% of patients with nail involvement achieved a site-specific Physician's Global Assessment of 0 or 1 (clear or almost clear). No serious adverse events were observed during the study. Our study supports the effectiveness of risankizumab in plaque psoriasis involving difficult-to-treat sites.

Background: Long-term real-life data on secukinumab use in psoriasis are limited., Objectives: Determine the long-term effectiveness of secukinumab in moderate-to-severe psoriasis in real-life., Methods: Multicenter retrospective study analyzing data from adult patients treated with secukinumab for at least 192 weeks and up to 240 weeks in Southern Italy, between 2016 and 2021. Clinical data, including concurrent comorbidities and prior treatments were collected. Effectiveness was assessed by Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), Dermatology Life Quality Index (DLQI) scores at the initiation of secukinumab and at weeks 4, 12, 24, 48, 96, 144, 192, and 240., Results: Two hundred and seventy-five patients (174 males), mean age 50.80 ± 14.78 years, were included; 29.8% had an uncommon localization, 24.4% psoriatic arthritis, 71.6% comorbidities. PASI, BSA, and DLQI improved significantly from week 4 and continued to improve over time. Between weeks 24 and 240, PASI score was mild (≤10) in 97-100% of patients, 83-93% had mild affected BSA (BSA ≤ 3), and 62-90% reported no effect of psoriasis on their quality of life (DLQI 0-1). Only 2.6% of patients reported adverse events and no patient discontinued the treatment during the study period., Conclusions: Secukinumab effectiveness in the long-term treatment of psoriasis is confirmed in real-world.

Background and Objective: The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment., Patients and Methods: Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021., Results: A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal., Conclusions: Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis., (© 2023 The Australasian College of Dermatologists.)

Background: Tildrakizumab (TIL) is an interleukin (IL)-23p19 inhibitor for the treatment of moderate-to-severe plaque psoriasis with long-term efficacy and safety demonstrated in Phase III trials. Studies conducted in conditions closer to clinical practice are needed., Objectives: The TRIBUTE study (open-label, Phase IV) assessed the efficacy and impact on health-related quality of life (HRQoL) of TIL 100 mg in adult moderate-to-severe psoriasis patients (naïve to IL-23/Th17 pathway inhibitors) in conditions similar to clinical practice., Methods: Key efficacy measure was Psoriasis Area Severity Index (PASI). HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) and Skindex-16. Additional patient-reported outcomes included Pain-, Pruritus- and Scaling-Numerical Rating Scale (NRS), Medical Outcome Study (MOS)-Sleep, Work Productivity and Activity Impairment (WPAI), Patient Benefit Index (PBI) and Treatment Satisfaction Questionnaire for Medication (TSQM)., Results: One hundred and seventy-seven patients were enrolled (six patients did not complete the study). After 24 weeks, the proportion of patients achieving PASI scores ≤ 3, PASI 75, PASI 90 and DLQI 0/1 was 88.4%, 92.5%, 74.0% and 70.4%, respectively. Skindex-16 overall score improved (mean absolute change from baseline, MACB [95%CI]: -53.3 [-58.1, -48.5]). Significant benefits (MACB [95%CI]) were found on pruritus-, pain- and scaling-NRS scores (-5.7 [-6.1, -5.2], -3.5 [-4.1, -3.0] and -5.7 [-6.2, -5.2], respectively), MOS-Sleep (-10.4 [-13.3, -7.4] Sleep problems Index II) and WPAI (-36.4 [-42.6, -30.2] activity impairment, -28.2 [-34.7, -21.7] productivity loss, -27.0 [-32.9, -21.1] presenteeism and -6.8 [-12.1, -1.5] absenteeism). 82.7% of patients reported PBI ≥ 3 and the mean (SD) global TSQM score was high (80.5 [18.5]). Only one serious treatment-emergent adverse event was reported (not-related to TIL)., Conclusions: TIL 100 mg treatment after 24 weeks in conditions close to real clinical practice showed a quick and high improvement in psoriasis signs and HRQoL. Patient reported improvements in sleep outcomes and work productivity, relevant benefits and high treatment satisfaction. The safety profile was favourable and consistent with Phase III trials., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Secukinumab is effective in treating patients with moderate-to-severe plaque psoriasis. However, most studies assessing its effectiveness in routine clinical settings in China are mostly single-center studies with a limited sample size. The objective of this study was to assess secukinumab's efficacy, treatment patterns, and characteristics in patients with moderate-to-severe plaque psoriasis. This 24-week, multicenter (n = 5) retrospective study analyzed the data of Chinese adult patients with moderate-to-severe plaque psoriasis who initiated secukinumab treatment between May 2019 and March 2020. The Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator's Global Assessment Modified 2011 (IGA mod 2011), and Dermatology Life Quality Index (DLQI) were assessed. Dermatologists documented the treatment dosage and modification reasons. Of the 244 secukinumab-naïve patients, most were men (73.4%, 179/244) and weighed 60-90 kg (72.8%, 177/243). The mean (SD) age at secukinumab initiation was 38.1 (11.6) years, and the disease duration was 13.5 (7.9) years. Most patients (97.1%, 237/244) received secukinumab 300 mg. At weeks 4, 12, 16, and 24, the proportion of patients achieving PASI 75 (≥75% reduction from baseline) was 40.0%, 92.1%, 88.4%, and 88.9%, respectively; PASI 90 was 15.0%, 73.7%, 81.4%, and 68.3%, respectively; and PASI 100 was 8.7%, 40.8%, 58.1%, and 41.3%, respectively. During the same periods, BSA and IGA mod 2011 showed similar improvement trends. An increasing proportion of patients achieved DLQI of 0-1 (21.6%, 65.7%, 75.0%, and 80.3%, respectively). Treatment modification was highest at week 12. The average interval between two administrations after week 4 was 62.95 days. Secukinumab was highly effective in improving the PASI, IGA, BSA, and DLQI in Chinese patients with moderate-to-severe plaque psoriasis throughout the first 24 weeks. The treatment pattern for Chinese patients differs from that in the clinical guidelines., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Monoclonal antibodies to interleukin (IL)-17 have shown strong efficacy in patients with psoriasis. Izokibep is a unique IL-17A inhibitor with a small molecular size and favourable distribution to sites of inflammation., Objectives: To evaluate the dose response, efficacy and safety of izokibep in patients with plaque psoriasis., Methods: In this double-blind, randomized, phase II dose-finding study (AFFIRM-35) in adults with moderate-to-severe plaque psoriasis and inadequate response to two or more standard therapies, patients were randomized (1:1:1:1:1) to placebo or izokibep 2, 20, 80 or 160 mg every 2 weeks for 12 weeks. During the remainder of the 52-week core study, patients given placebo were switched to izokibep 80 mg, and dosing intervals were adapted based on Psoriasis Area and Severity Index (PASI) scores for all patients. The core study was followed by two optional consecutive 1-year extension periods for a total duration of 3 years. The primary endpoint was a 90% reduction in PASI score (PASI 90) at week 12. Additional efficacy outcomes and adverse event (AE) rates were evaluated., Results: In total, 109 patients were randomized [safety set, n = 108 (one exclusion criteria failure); full analysis set, n = 106]. At week 12, PASI 90 response rates were 0%, 5%, 19%, 71% and 59% for the placebo, 2-, 20-, 80- and 160-mg izokibep groups, respectively. Rapid dose-dependent improvements were also observed across other efficacy outcomes. During the placebo-controlled period, AEs in the izokibep groups were similar to placebo except for mild injection site reactions. AEs were generally mild to moderate and the drug was well tolerated. Izokibep maintained efficacy at the higher dosage groups for up to 3 years, with no new safety signals., Conclusions: Data from this phase II study indicate that izokibep is well tolerated and efficacious in the treatment of plaque psoriasis. Higher doses or more frequent dosing could be explored to further enhance response rates., Competing Interests: Conflicts of interest: S.G. has received grants, contracts, honoraria, support for meetings/travel and/or participated in advisory or data safety monitoring boards for AbbVie, ACELYRIN, Affibody, Akari Therapeutics, Almirall-Hermal, Amgen, argenx, Aristea Therapeutics, Biogen Idec, Bioskin, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Hexal, Incyte, Janssen-Cilag, Johnson & Johnson, Klinge Pharma, Kymab, LEO Pharma, Medac, MSD, Neubourg Skin Care, Novartis, Pfizer, Pierre Fabre, Principia Biopharma, Regeneron Pharmaceutical, Sandoz Biopharmaceuticals, Sanofi-Aventis, Trevi Therapeutics and UCB Pharma; and has received equipment, materials, drugs, medical writing or other services from AbbVie, Almirall-Hermal, Amgen, Celgene, Eli Lilly, Janssen-Cilag, LEO Pharma, Medac, Novartis, Pfizer, Sanofi-Aventis and UCB Pharma. P.S. has received grants, contracts, honoraria, support for meetings/travel and/or has participated in advisory or data safety monitoring boards for AbbVie, Allergika, Almirall-Hermal, Amgen, Beiersdorf, Biocryst, BMS, Boehringer Ingelheim, Celgene, CSL-Behring, Eli Lilly, Galderma, Hexal, Janssen, Klinge, Klosterfrau, LEO Pharma, LETI Pharma, L’Oréal, Novartis, Octapharma, Pfizer, Pflüger, Pharming, Regeneron, Shire, Takeda, Regeneron, Sanofi-Genzyme und UCB Pharma. D.W. has received consulting fees from Affibody and ACELYRIN. M.A. has received grants, contracts and/or consulting fees from Arbeitsgemeinschaft Dermatologische Prävention (ADP) Education of Referees for certificate “Hautkrebs-Screening” issued by Zentralinstitut für Kassenärztliche Versorgung, Lumenis and various companies involved in laser treatments in dermatology. G.V. has received consulting fees from Affibody. J.F. is an employee of Affibody, owns stock in Affibody and is a patent holder of five patents involving interleukin-17A-binding and albumin-binding polypeptides. L.O.K., S.O. and N.C.B. are employees of Affibody and have stock options for Affibody. P.P. is an employee of ACELYRIN and has stock options for ACELYRIN. F.Y.F. is an employee of Affibody, owns stock in Affibody and has stock options for Affibody. T.D., O.W., J.N., R.d.M, and A.R. declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144)., Objectives: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials., Methods: The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and ≥ 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125)., Results: A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and ≥ 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; ≥ 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; ≥ 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab., Conclusions: Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients., Gov Identifier: NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023., (© 2023. The Author(s).)

Background: Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its off-label use are limited, especially regarding the optimal drug dosage regimen for different patient profiles., Objective: The main objective of this real-world, single-centre, retrospective study was to identify the off-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efficacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed definition., Methods: The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efficacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥  18 years and had moderate to severe plaque psoriasis., Results: The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index (PASI) was 10.1 and decreased to 2.1 between Week 11-20 without significant changes in the PASI value throughout the 90 weeks of follow-up. The cumulative probability of drug survival was 93.5% at Week 52. No differences were found in terms of efficacy and survival associated with the off-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bio-naïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment., Conclusion: The study demonstrated that off-label use of guselkumab was safe and effective in real-life clinical practice. The findings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in different patient profiles, especially in SR and bio-naïve patients. Further studies are needed to confirm these findings., (© 2023. The Author(s).)

Background: Interleukin (IL) 23p19 monoclonal antibodies were efficacious and safe in the treatment of psoriasis. A first-in-human (FIH) study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of IBI112, a novel IL-23p19 monoclonal antibody., Methods: In this FIH, randomized, double-blind, placebo-controlled, single-ascending-dose study, a subcutaneous (SC, 5-600 mg) or intravenous (IV, 100 and 600 mg) or placebo was administered to eligible healthy subjects. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Furthermore, non-compartment analysis and population PK modeling were conducted to characterize PK, and model-based simulation was applied to justify dose selection for psoriasis patients., Results: A total of 46 subjects were enrolled, with 35 receiving IBI112 and 11 receiving placebo. No serious adverse events (SAEs) and no clinically significant adverse events were identified. After a single SC of IBI112, the median T max was 4-10.5 days, and the half-life (t 1/2 ) ranged from 21.8 to 35.8 days. IBI112 exposures (C max and AUC inf ) approached dose proportionality across 5-300 mg range., Conclusion: IBI112 was well tolerated and safe at SC or IV dose up to 600 mg and showed a linear PK characteristics at SC dose from 5 to 300 mg., Clinical Trial Registration: ClinicalTrial.gov NCT04511624.

Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious role in the pathogenesis of psoriasis, in addition to specific immunological molecules such as TNF-, IL-12, IL-23, IL-17, and other molecules that can aid in the pathogenesis of psoriasis. So, during the past two decades, biologists have created chemical drugs that target these cells or molecules and therefore prevent the disease from occurring. Alefacept, efalizumab, Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. It was discovered that these chemical drugs have long-term side effects that can cause defects in the patient's body, such as the development of the rare but life-threatening disorder progressive multifocal leukoencephalopathy (PCL). Its rapidly progressive infection of the central nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies (ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have few or no side effects on the patient's body., (© 2023. The Author(s).)

BI 730357 is investigated as an oral treatment of plaque psoriasis. We analyzed the impact of three dosage regimens on the Psoriasis Area and Severity Index (PASI) response with modeling based on phase I and II data from 109 healthy subjects and 274 patients with moderate-to-severe plaque psoriasis. The pharmacokinetics (PK) was characterized by a two-compartment model with dual absorption paths and a first-order elimination. Higher baseline C-reactive protein was associated with lower clearance and patients generally had lower clearance compared with healthy subjects. A bounded integer PK/pharmacodynamic model characterized the effect on the observed PASI. The maximum drug effect was largest for patients with no prior biologic use, smaller for patients with prior use of non-interleukin-17 inhibitors, and smallest for patients with prior interleukin-17 inhibitor use. The models allowed robust simulation of large patient populations, predicting a plateau in PASI outcomes for BI 730357 exposure above 2000 nmol/L., (© 2023 Pharmetheus AB and The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Given the chronic nature of psoriasis and the loss of response that can be observed with therapies over time, it is important to understand the long-term efficacy of new treatments., Objectives: To evaluate maintenance of Week 16 responses with bimekizumab (BKZ) treatment through Year 3, in patients with moderate-to-severe plaque psoriasis., Methods: Data were pooled from BKZ-treated patients in the 52-week (BE VIVID) and 56-week (BE READY and BE SURE) phase III studies, and their ongoing open-label extension (OLE), BE BRIGHT. Efficacy outcomes are reported through 3 years of BKZ treatment in patients with an efficacy response at Week 16. Missing data were imputed primarily using modified nonresponder imputation (mNRI), with nonresponder imputation and observed case data also reported., Results: A total of 989 patients were randomized to BKZ at baseline in BE VIVID, BE READY and BE SURE. At Week 16, 693 patients achieved ≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90), 503 achieved 100% reduction from baseline in PASI (PASI 100), 694 achieved absolute PASI ≤ 2 and 597 achieved body surface area (BSA) ≤ 1%, and continued into the OLE. Of these, 93.0% maintained PASI 90, 80.8% maintained PASI 100, 94.0% maintained PASI ≤ 2 and 90.3% maintained BSA ≤ 1% responses through to 3 years of BKZ treatment (mNRI). Among Week 16 PASI 90 responders, 96.8% and 72.5% also achieved Investigator's Global Assessment 0/1 and PASI 100 at Week 16, respectively, and 92.2% and 73.4% achieved these responses at Year 3 (mNRI). Among Week 16 PASI 100 responders, 76.3% also achieved Dermatology Life Quality Index (DLQI) 0/1 at Week 16, and DLQI 0/1 response increased with continuous BKZ treatment to 89.0% at Year 3 (mNRI)., Conclusions: High levels of clinical response were maintained through to 3 years of BKZ treatment in the vast majority of Week 16 responders. Long-term treatment with BKZ was efficacious, with important benefits for health-related quality of life, in patients with moderate-to-severe plaque psoriasis., Competing Interests: Conflicts of interest B.S.: Consultant (honoraria) from AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio and vTv Therapeutics; Stock options in Connect Biopharma and Mindera Health; Speaker for AbbVie, Eli Lilly, Janssen, Regeneron and Sanofi; Scientific Co-Director (consulting fee) from CorEvitas (formerly Corrona) Psoriasis Registry; Investigator for AbbVie, Cara Therapeutics, CorEvitas Psoriasis Registry, Dermavant, Dermira and Novartis; Editor-in-Chief (honorarium) of Journal of Psoriasis and Psoriatic Arthritis. Y.T.: Honoraria and/or grants from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical and UCB Pharma. U.M.: Served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from AbbVie, Almirall, Aristea, Boehringer Ingelheim, Celgene, Dr Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, Novartis, Phi-Stone, Pierre Fabre, Sanofi and UCB Pharma. M.L.: Employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, Incyte, Janssen, LLC, Ortho Dermatologics, Regeneron and UCB Pharma; Consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas (formerly Corrona), Dermavant, Dr Reddy’s Laboratories, Evelo Biosciences, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy and Verrica. P.F.: Grant support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sanofi and Sun Pharma; Investigator for AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Evelo Biosciences, Galderma, Genentech, Geneseq, GenesisCare, GSK, Hexima, Janssen, Kymab, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma and Valeant; served on advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma and Valeant; served as a consultant for Aslan, Bristol Myers Squibb, Eli Lilly, Galderma, GenesisCare, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Novartis, Pfizer, Roche, UCB Pharma and Wintermute; received travel grants from AbbVie, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sun Pharma and Sanofi; served as a speaker for or received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma and Valeant. R.G.L.: Principal Investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis and Pfizer. R.B.W.: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis and UCB Pharma; honoraria from Astellas, DiCE, GSK and Union. M.W., V.V., B. Szilagyi.: Employees and shareholders of UCB Pharma. V.C.: Employee of UCB Pharma. C.P.: Consulting fees and/or grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen Cilag, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi and UCB Pharma., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Introduction: Generalized pustular psoriasis (GPP) is a rare cutaneous and systemic inflammatory disease which is characterized by flares of widespread painful pustulation of the skin, often associated with fever and elevated inflammatory markers. Although it has historically been regarded as a severe variant of plaque psoriasis, genetic and immunological developments over the past decade have revealed that it is a distinct auto-inflammatory entity, in which over-activity of the interleukin-36 signaling pathway is fundamental. Treatments targeting the IL-36 pathway are under investigation, and in 2022 spesolimab, a monoclonal antibody against the IL-36 receptor, was licensed for treating flares of GPP., Areas Covered: In this review I discuss the epidemiology, clinical features, genetics, patho-mechanisms, and current treatment options for GPP. I describe the results of clinical trials that led to the licensing of spesolimab for flares of GPP., Expert Opinion: The marked efficacy of spesolimab in GPP opens a new era of highly effective, scientifically-rational, and evidence-based treatment for this orphan disease, and has implications for other diseases in which interleukin 36 signaling is involved.

Introduction: Prior studies have demonstrated guselkumab improves disease activity and patient-reported outcomes (PROs) among patients with moderate-to-severe plaque psoriasis. However, the real-world effectiveness of guselkumab across different subgroups [e.g., body mass index (BMI) categories] remains an area of active research., Methods: This study included patients enrolled in the CorEvitas Psoriasis Registry between July 18, 2017 and March 10, 2020 who had moderate-to-severe psoriasis [Investigator's Global Assessment (IGA) score ≥ 3], initiated guselkumab at a registry visit (index date), and had a follow-up registry visit after persistent guselkumab therapy for 9-12 months. Patients were stratified into three BMI categories: obese (≥ 30 kg/m 2 ), overweight (25- < 30 kg/m 2 ), and underweight/normal weight (< 25 kg/m 2 ). Response rates and mean changes for disease activity outcomes and PROs at follow-up were assessed within each BMI category., Results: Of the 180 patients included in the study, 101 (56%) were obese, 52 (29%) were overweight, and 27 (15%) were underweight/normal weight. Among the obese, overweight, and underweight/normal weight patients, 57%, 58%, and 72%, respectively, achieved an IGA score of 0/1 after 9-12 months of persistent guselkumab treatment. An IGA score of 0 was achieved by 33%, 35%, and 48% of obese, overweight, and underweight/normal weight patients, respectively. A 90% improvement in the Psoriasis Area and Severity Index was achieved by 46%, 46%, and 56% in these respective subgroups. Mean improvements in disease activity and PRO scores were similar among BMI subgroups., Conclusion: The results of this real-world study showed improvements in disease severity and several PRO scores within all BMI categories among patients with moderate-to-severe psoriasis treated with guselkumab. These unadjusted findings suggest that obese and overweight patients have comparable absolute improvements to those with lower BMI; however, they may be less likely to achieve relative endpoints. Additional analyses are needed to fully characterize this relationship., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: Real-world data are useful to guide the management of psoriasis. Here, we present data on the effectiveness and survival of guselkumab in moderate-to-severe chronic plaque psoriasis for up to 148 weeks., Research Design and Methods: Cross-sectional study of 122 patients receiving guselkumab (100 mg at weeks 0 and 4, and then every 8 weeks thereafter) for>12 weeks, from November 2018 to April 2022., Main Outcome Measures: Clinical features and drug survival were analyzed up to 148 weeks., Results: Obese patients (32.8%) and those receiving prior biologics (64.8%) were included. Guselkumab treatment was associated with a rapid decrease in PASI, from 16.2 to 3.2 at week 12, and long-term improvements in all subgroups (97.6%, 82.9%, and 63.4% of patients, respectively, achieved PASI 75, 90, and 100 after 148 weeks). More non-obese than obese patients achieved PASI 100 at week 148 (86.4% vs 38.9%), as did bio-naïve vs bio-experienced patients (86.7% vs 50.0%). Previous biologic therapy was a negative prognostic factor for achieving PASI 100 over the long-term by multivariate analysis ( p  = 0.005). Overall, 96% of patients were on treatment after 2 years., Conclusions: Real-world data confirm the long-term effectiveness of guselkumab in patients with psoriasis.

Background: Real-world studies on the use of biologics in psoriasis (Pso) are increasing, but still scarce. Trough concentrations (C t s) of interleukin-17 inhibitors (IL-17i) seem promising for clinical decision-making, but their value in daily practice has yet to be proven., Objectives: To report on IL-17i effectiveness, treatment modifications and C t use in our clinic., Methods: Data were collected from IL-17i-treated Pso patients followed up in the PsoPlus clinic at the Dermatology department, Ghent University Hospital, Belgium. Descriptive statistics and Kaplan-Meier analysis were performed., Results: A total of 111 patients were included, counting for 134 IL-17i courses (secukinumab, ixekizumab, and brodalumab). Fifty-five per cent of the patients were bio-naive prior to IL-17i initiation. During maintenance, merely 97.0% and 77% achieved near-complete and complete skin clearance, respectively. Major reasons for treatment modification were suboptimal response (63.0%) and safety issues (9.3%). Reported modifications were switch (25.4%), dose escalation (11.9%), dose de-escalation (6.7%), treatment association (6.0%) and IL-17i stop (3.0%). Overall drug survival was 69.0 months, without difference between the different IL-17i (p = 0.078). Ixekizumab tended to have the highest survival. Drug survival was higher in bio-naive subjects compared to bio-experienced subjects (p = 0.011). C t was measured in 20 patients and interpreted post hoc. In 85%, the clinical decision was in accordance with the C t (e.g. substantiated need for dose escalation). For the other cases, the C t would have led to another clinical decision if known at that time., Conclusions: This real-world study showed that IL-17i are very effective drugs for Pso, with ixekizumab as leading biologic. Prior bio-experience seemed to impact IL-17i drug survival. Treatment modifications were mainly performed in case of insufficient response, primarily via switch and dose escalation, and least frequently in ixekizumab patients. C t might rationalize clinical decision-making; however, there is need for standardized algorithms to corroborate its use., (© 2022 European Academy of Dermatology and Venereology.)

Introduction: The therapeutic armamentarium for the treatment of psoriasis, a chronic inflammatory skin disease, is now reasonably broad and structured, with several therapeutic agents that demonstrated a successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of the existing ones., Areas Covered: The aim of this review is to thoroughly explore new therapeutic strategies and novel drugs that are currently in the pipeline for the treatment of psoriasis, focusing primarily on agents that are currently in phase I/II of clinical development. Some of which retrace already existing therapeutic approaches, such as the IL23/Th17 pathway inhibition, while others unveil new and yet unexplored ones., Expert Opinion: Since the therapeutic landscape of psoriasis is wide, it is not yet clear whether novel agents will fill the remaining gaps in the context of a broader and more diversified set of oral and biologic therapies. Nevertheless, with the development of precision medicine approaches, the development of innovative targeted drugs will still have a therapeutic rationale in psoriasis.

Biologic medications have revolutionized treatment of psoriasis; however, there remains uncertainty in which medications should be used to maximize efficacy based on race/ethnicity. The purpose was to determine if efficacy of biological medications differs based on race/ethnicity. A systematic review identified all clinical trials focused on biologic treatment outcomes from inception of database until March 5th, 2021. Included studies provided data on racial/ethnic differences in biologic skin clearance efficacy using the Psoriasis Area and Severity Index (PASI) and "clear/almost clear" scores. There were 1220 studies identified, and 24 included in the review. The races/ethnicities included were Asian (n = 2740), White (n = 9745), Black (n = 138), and Latino (n = 728). Ixekizumab provided the highest "clear/almost clear" score (90.7%, 89.4%) and PASI 75 (98.8%, 96.6%) for Asian and Latino patients, respectively. Guselkumab had the highest "clear/almost clear" score for White (86.8%) patients, while Black patients had highest "clear/almost clear" (75.0%) and PASI 75 (91.7%) scores to brodalumab. Limitations included lack of studies reporting outcome data based on race/ethnicity and lack of patients of color within psoriasis clinical trials. For treatment of plaque psoriasis, there is evidence of differences in efficacy of biologics improving clinical disease severity between different races or ethnicities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Secukinumab demonstrated high efficacy and favorable safety profile in patients with moderate-to-severe plaque psoriasis (PsO) in clinical trials. However, understanding of patient characteristics and clinical outcomes in real world in Thailand is still limited. To describe patient characteristics, effectiveness and safety of secukinumab in Thai PsO patients. This retrospective study analyzed data from medical records of adult PsO patients who initiated secukinumab at 7 dermatology centers from September 2017 to April 2021. Study outcomes included patient characteristics and changes in Psoriasis Area and Severity Index (PASI) score from baseline at weeks 4 and 16 after secukinumab initiation. Adverse events were recorded. Subgroup analyses by adherence rate and completeness of loading dose were performed. Of 163 patients, the mean (SD) age was 44.0 (14.0) years. Most patients (84.7%) were previously treated with topical therapy while 62.0% and 21.5% of patients had received systemic and biologic therapy, respectively. The mean baseline PASI score was 15.4 (9.3). Overall, the mean PASI score improved by 58.0% at week 4 and 78.4% at week 16. Statistically significant differences in PASI approvement were revealed among subgroups of patients with different loading dose and adherence rate. Adverse effects were reported in 8.0% of patients. The characteristics of patients in this study were slightly different from clinical trials in terms of demographic and clinical characteristics, as well as PsO treatment. Secukinumab was effective and safe in Thai patients with PsO, especially among those with complete loading dose and a higher adherence rate., (© 2022 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months)., (© 2022 Wiley Periodicals LLC.)

Secukinumab is a recombinant, fully human monoclonal anti-IL-17A antibody approved to treat moderate-to-severe psoriasis and psoriatic arthritis. Its effectiveness and safety have been confirmed, but a gradual increase in the secukinumab dosing interval has not been investigated. To assess the feasibility, efficacy, and safety of gradually increasing the secukinumab dosing interval; the interval duration was determined by changes in the Psoriasis Area and Severity Index scores. Patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 0, 1, 2, and 3. At week 4, the improvement from baseline PASI guided the next injection time until week 36. In total, 83 patients were recruited. PASI 75 was achieved by 80%, 96%, and 95% of patients at weeks 4, 12, and 36, respectively. PASI 90 was achieved by 54%, 95%, and 84% of patients at weeks 4, 12, and 36, respectively. PASI 100 was achieved by 28%, 89%, and 68% of patients at weeks 4, 12, and 36, respectively. The average PASI score (1.05 ± 1.83) was significantly lower at week 36 than at baseline. Most patients reached PASI 75 at week 36 in our modified study. This study may provide information for future biotherapies., (© 2022 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Background: Real-world data on guselkumab, especially at times >6 months, are limited., Research Design and Methods: We performed a longitudinal, retrospective analysis on 307 patients with moderate-severe chronic plaque psoriasis (Psoriasis Area Severity Index [PASI] >10) treated with guselkumab for up to 12 months., Main Outcome Measures: PASI 75, PASI 90, and PASI 100 were assessed at baseline and at 4, 12, 20, 28, 36, 44, and 52 weeks., Results: At 12 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 56.4%, 33.6%, and 24.1% of patients, respectively. At 52 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 82.7%, 68.7%, and 51.1% of patients, respectively. Patients without comorbidities and those naïve to previous biological therapy had better responses. The mean Dermatology Life Quality Index score decreased from 14.0 at baseline to 3.1 at 12 weeks and 1.6 at 6 months, which was maintained at later times. Similar improvements were seen in pruritus visual analog scale., Conclusions: Guselkumab maintains its efficacy for up to 12 months among responders in a real-world cohort of patients with moderate-severe plaque psoriasis, confirming data from prior real-world studies with smaller cohorts and shorter duration of follow-up.

Bimekizumab, a selective interleukin (IL) 17 inhibitor, is an emerging systemic treatment for moderate-to-severe psoriasis. Although IL-19, IL-22, and IL-36 are implicated in the pathogenesis of psoriasis, IL-17 drives the activation of these interleukins and the formation of psoriatic plaques. This review assesses the efficacy, safety, and implications of bimekizumab in the treatment of moderate-to-severe psoriasis. A review of literature was conducted using the PubMed repository in March 2022. Articles in English discussing the use of bimekizumab in the treatment of psoriasis were included. One phase II and four phase III trials were included. During clinical trials, bimekizumab was more efficacious, when compared to placebo, ustekinumab, adalimumab, and secukinumab in the treatment of moderate to severe psoriasis. Bimekizumab is a promising, efficacious, and relatively tolerable emerging systemic treatment for moderate-to-severe plaque psoriasis.

Background: Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease., Objectives: To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO)., Methods: SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years., Results: In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m 2 were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed., Conclusions: Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

The IL23/Th17 axis plays a strategic role in psoriasis (PSO). Guselkumab (GUS) is a selective inhibitor of the IL23p19 subunit. Its introduction has managed to increase the levels of efficacy, safety and survival in PSO. In real clinical practice, patients can loss effectiveness or suffered adverse events that forces a change in their treatments. There is scarce evidence of the effectiveness, safety, and survival of GUS in real clinical practice after anti-TNFα, anti-IL17, and/or anti-IL12/23. This is multicenter, observational and retrospective study of real clinical practice includes patients with moderate-to-severe plaque PSO in treatment with GUS. The objective of the study was to evaluate the effectiveness of GUS after anti-TNFα, anti-IL17, and anti-IL12/23. The study includes clinical information from February 2019 to February 2022. PASI, BSA, Pruritus, DLQI, survival, and safety were evaluated up to 76 weeks. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. A total of 103 patients were included in the analysis. At baseline there were significant differences between the anti-TNF, anti-IL17, and anti-IL12/23 groups for (1) dyslipidemia; (2) number of previous biological treatments and (3) PASI, BSA, VAS Pruritus, and DLQI scores. The effectiveness of GUS in terms of PASI, BSA, Pruritus, and DLQI was not impacted by previous biological alternatives. Treatment survival including discontinuations due to lack of effectiveness or safety reasons was 100%, 92.7%, and 92.1% for anti-TNFα, anti-IL17, and anti-IL12/23, respectively, at 130 weeks. No differences were found between groups. One adverse event was reported in the anti-LI12/23 group. The mid-term effectiveness, safety and survival of GUS if not impacted by previous biological therapy as anti-TNFα, anti-IL17, and/or anti-IL12/23. Our results indicate that GUS could be a switching strategy in patients who fail or present AE to other biological alternatives in moderate-to-severe PSO., (© 2022 Wiley Periodicals LLC.)