Application of the interleukin-23 inhibitor guselkumab in the treatment of psoriasis / 中华皮肤科杂志

Guselkumab is the first monoclonal antibody that selectively targets interleukin (IL) -23. Several randomized controlled clinical trials have demonstrated that it is highly effective and safe in the treatment of moderate to severe plaque psoriasis, and can significantly improve the quality of life of patients. This review summarizes the action mechanisms of IL-23 and guselkumab, as well as the application of guselkumab in the treatment of psoriasis.

Tratamiento exitoso con risankizumab en paciente con psoriasis y HIV / Successful treatment with risankizumab in a patient with psoriasis and HIV

Resumen El tratamiento de la psoriasis en pacientes HIV positivos resulta un desafío, ya que pueden requerir tratamientos sistémicos de carácter inmunosupresor tales como con agentes biológicos, lo que conlleva a un mayor riesgo de infecciones. Se presenta el caso de un paciente HIV positivo con psoriasis grave sin compromiso artropático, refractaria a otros tratamientos. Existen datos limitados sobre el uso de terapias biológicas en pacientes HIV positivos, pero algunos informes de caso sugieren que su uso es eficaz y seguro. Específicamente, la aparición de anticuerpos monoclonales selectivos para la interleucina 23 tales como risankizumab, pueden ofrecer una terapéutica segura y eficaz para pacientes HIV positivos con psoriasis refractaria a otros tratamientos. De todas maneras, se requieren estudios controlados para definir por completo su seguridad y eficacia.

Abstract The treatment of psoriasis in HIV-positive patients is challenging, as they may require systemic immunosuppressive treatment such as biological agents, leading to an increased risk of infections. A case report of an HIV positive patient with severe psoriasis without arthropathic compromise, refractory to other treatments, is presented. There are limited data on the use of biological therapies in HIV-positive patients, but isolated case reports suggest that their use is effective and safe. Specifically, the emergence of monoclonal antibodies selective for interleukin 23 such as risankizumab may offer a safe and effective therapy for HIV-positive patients with psoriasis refractory to other treatments. In any case, controlled studies are required to fully define its safety and efficacy.

Atualização do custo-efetividade por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe no tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / An update of a cost-effectiveness per response of adalimumab, etanercept, guselcumab, infliximab, ixekizumab, secukinumab and ustekinumab for treatment of moderate to severe plaque psoriasis from the perspective of the Brazilian Supplementary Health System

Objetivo: Os agentes biológicos representam um grande avanço no tratamento da psoríase em placas moderada a grave. No entanto, variações de eficácia, segurança e custos dos tratamentos podem dificultar a escolha do agente terapêutico. Este estudo teve como objetivo atualizar o custo por resposta dos agentes biológicos disponíveis para psoríase no ROL de Procedimentos e Eventos em Saúde (ROL) da Agência Nacional de Saúde Suplementar (ANS). Métodos: Uma análise de custo por resposta foi utilizada para avaliar a razão de custo pelo desfecho Índice de Gravidade e Área da Psoríase (PASI) 90. Os resultados foram apresentados para o primeiro ano (ano I), que compreende a fase de indução e a fase manutenção até completar 52 semanas e foi realizada uma análise da efetividade do tratamento num cenário de orçamento fixo. Os custos dos tratamentos foram calculados com base nos preços de fábrica (PF18%) da Tabela da Câmara de Regulação do Mercado de Medicamentos de junho de 2021. Resultados: Para o ano I, o guselcumabe apresentou melhor resultado para custo por resposta (R$ 130.467) PASI 90, seguido por ixequizumabe, ustequinumabe, secuquinumabe, adalimumabe, infliximabe e etanercepte. No cenário com orçamento fixo, o guselcumabe demonstrou ser o agente capaz de tratar com sucesso (PASI 90) o maior número de pacientes. Atualização do custo-efetividade por resposta para psoríase em placas moderada a grave. Conclusão: Sob a perspectiva do Sistema de Saúde Suplementar do Brasil, o guselcumabe apresentou o melhor custo por resposta PASI 90, sendo, assim, a terapia com melhor custo-efetividade no tratamento da psoríase em placas moderada a grave disponível no ROL.

Objective: Biological agents represent a major advance in the treatment of moderate-to-severe plaque psoriasis. However, variations of efficiency, safety and costs of treatments make it difficult to select the drug. This study aims to update the cost per response of biological agents available in the Health Procedures and Events Roll (ROL) of the National Supplementary Health Agency (ANS). Methods: A cost-per-response analysis was used to assess the cost per outcome of Psoriasis Area and Severity Index (PASI) 90. Results were presented for the first year (I), which comprises induction and maintenance for 52 weeks and a fixed budget scenario analysis. Treatment costs were calculated based on the prices of the 2021 Medicines Market Regulation Chamber Table. Results: Analysis of year I, guselkumab showed the best result for cost per cost (R$ 130,467) PASI 90, followed by ixekizumab, ustekinumab, secukinumab, adalimumab, infliximab, and etanercept. In the fixedbudget analysis, guselkumab is the therapy capable of successfully treating (PASI 90) the largest number of patients. Conclusion: From the perspective of the Supplementary Health System in Brazil, guselkumab showed the best cost per response PASI 90, thus being the most cost-effective therapy in the treatment of moderate to severe plaque psoriasis available in the Brazilian ROL.

Efficacy and Safety of Guselkumab in the Treatment of Moderate-to-severe Plaque Psoriasis ：A Systematic Re- view / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and safety of guselkumab in the treatment of moderate-to- severe plaque psoriasis ，and to provide evidence-based reference for the clinical treatment. METHODS ：Retrieved from PubMed ， Embase，Cochrane Library ，CNKI，VIP，Wanfang database during inception to Oct. 2019，randomized controlled trials （RCTs） about guselkumab versus placebo/positive control in the treatment of moderate-to-severe plaque psoriasis were collected. After literature screening and data extraction ，quality evaluation was performed by using the bias risk evaluation tool recommended by the Cochrane System evaluator manual 5.1.0. Meta-analysis was performed by using Stata 16.0 software. RESULTS ：Eight RCTs with a total of 3 488 patients were included. The results of Meta-analysis indicated that the proportion of patients who achieved 90％ reduction or more from baseline of psoriasis area and severity index （PASI）in guselkumab group was significantly higher than that placebo group [RR ＝26.72，95％CI（15.98，44.70），P＜0.001]，adaliumumab group [RR ＝1.45，95％CI（1.32，1.59）， P＜0.001] and secukinumab group （P＜0.000 1）. The proportion of patients with Investigator ’s Global Assessment （IGA）score of 0 or 1 in guselkumab group was significantly better than placebo group [RR ＝11.15，95％ CI（8.22，15.14），P＜0.001] and adaliumumab group [RR ＝1.27，95％CI（1.19，1.35），P＜0.001]. The proportion of patients with IGA score of 0，the proportion of patients who achieved 75％ reduction or more from baseline of PASI ，dermatology life qu ality index score of 0 or 1 in guselkumab group were signifi cantly superior than placebo group and adaliumumab gr oup，the proportion of patients who achieved 100％ reduction from baseline of PASI in guselkumab group Lewx- was significantly superior than placebo group （P＜0.05）， inn@outlook.com there was no significant difference compared with adaliumumab group （P＞0.05）. There was no statistical significance in the proportion of patients with IGA score of and other secondary outcome indicators between guselkumab and secukinumab group （P＞0.05）. In the safety indicators as total incidence rate of ADR ，rate of withdrawl due to ADR ，etc. ，there was no statistical significance between guselkumab and placebo/ adalimumab groups （P＞0.05）. CONCLUSIONS ：Guselkumab is superior to placebo ，adaliumumab and secukinumab in improving the symptoms of moderate-to-severe plaque psoriasis with good safety .

Guselkumab in moderate-to-severe plaque psoriasis: effectiveness in real clinical practice / Guselkumab en placa de moderada a grave psoriasis: eficacia en la práctica clínica real

Introducción: La psoriasis es una enfermedad cutánea inflamatoria crónica inmunomediada que afecta a casi el 1-2% de la población mundial. El tratamiento biológico de la psoriasis moderada a grave ha cambiado el paradigma de manejo de la enfermedad, permitiendo un mejor control de la misma. Métodos: Se llevo a cabo un estudio observacional retrospectivo que incluyó a pacientes con psoriasis moderada a grave que fueron tratados durante al menos 36 semanas con guselkumab. La eficacia se evaluó mediante la estimación de pacientes que alcanzaron las respuestas PASI 75, PASI 90 y PASI 100 en las semanas 16, 24 y 36. Se utilizó la prueba T de Student para muestras pareadas para determinar la significación estadística entre PASI al inicio y respuesta PASI en las semanas 16, 24 y 36. Resultados: Se incluyeron 22 pacientes, 14 mujeres (63, 6%), con una edad media de 48, 7 ± 15, 5 años. El tratamiento con guselkumab redujo el PASI medio de 10, 3 ± 6 al inicio del estudio a 2, 4 ± 2 (p = 0,003), 1, 3 ± 1, 8 (p = 0,001) y 0, 3 ± 0, 6 (p = 0,001) a las 16, 24 y 36 semanas, respectivamente. Discusión: El primer fármaco en unirse al arsenal terapéutico anti-IL23 fue guselkumab. La eficacia obtenida fue superior a la observada en estudios fase III para PASI 90 y 100 a la semana 36. Existen algunos estudios que han evaluado la eficacia a corto plazo de guselkumab en la práctica clínica real; sin embargo, este fármaco se ha comercializado recientemente, limitando la posibilidad de evaluación durante períodos de tiempo más prolongados. Conclusión: Guselkumab presenta buenos resultados en el manejo de la psoriasis en adultos. La práctica clínica real a medio y largo plazo será fundamental, con un mayor tamaño muestral y período de seguimiento.

Introduction: Psoriasis is a chronic immune­ mediated inflammatory skin disease that affects nearly 1­2% of the population worldwide. Biologic treatment of moderate-to-severe psoriasis has changed the disease management paradigm, allowing for better disease control. Methods: A retrospective observational study including patients with moderate-to-severe psoriasis who were treated for at least 36 weeks with guselkumab. Efficacy was evaluated by estimating the proportion of patients achieving PASI 75, PASI 90 and PASI 100 responses at weeks 16, 24 and 36. The Student t-test for paired samples was used to determine the significant difference in outcome of patients between PASI at baseline and PASI response at weeks 16, 24 and 36. Reslts: 22 patients were included, 14 women (63.6%), with mean age of 48.7±15.5. Guselkumab treatment decreased mean PASI from 10.3±6 at baseline to 2.4±2 (p=0.003), 1.3±1.8 (p=0.001) and 0.3±0.6 (p=0.001) at 16, 24 and 36 weeks, respectively. Discussion: The first anti-IL23 drug family to join the therapeutic arsenal is guselkumab. The efficacy obtained is higher than that observed in phase III studies for PASI 90 and 100 at week 36. There are some studies that have evaluated the short-term effectiveness of guselkumab in real clinical practice; however, this drug has only recently been marketed, limiting the possibility of as yet longer treatment periods. Conclusion: Guselkumab shows great results in the management of psoriasis in adults. Medium- and long-term real clinical practice will be essential, with a larger sample size and longer follow-up period.

Analise de custo por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe para tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / Cost per response analysis of adalimumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab and ustekinumab for the treatment of moderate to severe plaque psoriasis from the Brazilian private health care system perspective

O OBJETIVO: deste estudo é avaliar o custo por resposta das terapias biológicas disponíveis no Brasil para o tratamento da psoríase em placas moderada a grave na perspectiva do Sistema de Saúde Suplementar. MÉTODOS: A resposta PASI 90 foi o desfecho avaliado neste estudo. Dados clíni-cos foram calculados com base na razão de risco de uma metanálise em rede, comparando adalimu-mabe, etanercepte, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe a guselcumabe, cujo dado foi obtido no estudo clínico. Foram considerados apenas os custos de medicamentos. O caso-base avaliou o custo por resposta do ano de indução do tratamento. Além disso, conduziu-se uma análise de orçamento fixo. Em um cenário alternativo, analisou-se o custo por resposta do ano de manutenção. Uma análise de sensibilidade avaliou incertezas dos dados clínicos. RESULTADOS: O menor custo por resposta foi de guselcumabe (R$ 98.643), seguido de ixequizumabe (R$ 112.549), ustequinumabe (R$ 124.078), secuquinumabe (R$ 160.930), infliximabe (R$ 208.039), adalimumabe (R$ 208.686) e etanercepte (R$ 639.124). Resultados similares foram observados no cenário alterna-tivo, considerando os custos no ano de manutenção. Guselcumabe demonstrou ser a terapia que tratou mais pacientes com sucesso, considerando um cenário de orçamento fixo. Conclusão: O presente estudo demonstrou que, na perspectiva do Sistema de Saúde Suplementar brasileiro, gu-selcumabe possui o menor custo por resposta entre as terapias biológicas para psoríase em placas moderada a grave, além de tratar com sucesso mais pacientes em um cenário de orçamento fixo.

Objective: This study aims to evaluate the cost per response of the biologic therapies available for moderate to severe plaque psoriasis treatment in Brazil from a private payer perspective Methods: Treatment response evaluated in this study was the achievement of PASI 90. Clinical data was calculated based on the risk ratio of a network meta-analysis comparing adalimumab, etanercept, infliximab, ixekizumab, secukinumab and ustekinumab to guselkumab, which data was extracted from clinical trials. Only drug acquisition cost were considered. Base case analysis evaluated the first year of treatment cost per response Besides that, a fixed budget analysis was conducted. An alternative scenario analysis considered the maintenance year cost per response. A sensitivity analysis evaluated the clinical data uncertainties. Results: The lowest cost per response was obtained with guselkumab (R$98.643), followed by ixekizumab (R$ 112.549), ustekinumab (R$ 124.078), secukinumab (R$ 160.930), infliximab (R$ 208.039), adalimumab (R$ 208.686), and etanercept (R$ 639.124). Similar results were found in the alternative scenario, with maintenance year costs. Guselkumab demonstrated to be the therapy which successfully treats more patients with a fixed budget. Conclusion: In conclusion, this study demonstrated that, from the Brazilian private payer perspective, guselkumab presents the lowest cost per response among the avail-able biologic therapies for moderate to severe plaque psoriasis, and is able to successfully treat more patients in a limited budget scenario.