Tromboembolia pulmonar masiva en un paciente con enfermedad de Crohn y tuberculosis latente tratada con ustekinumab

La enfermedad inflamatoria intestinal (EII) es un espectro de enfermedades crónicas inmunomediadas que afectan tanto el tracto gastrointestinal, como otros sistemas extraintestinales, comportándose como una enfermedad sistémica. Los fenómenos tromboembólicos son una complicación frecuente en la EII, como consecuencia de los estados de hipercoagulabilidad que se asocian con la actividad de la enfermedad, y su aparición tiene un impacto negativo tanto en el pronóstico como en la sobrevida de los pacientes. Debido a ello, el control de la actividad inflamatoria de la EII es uno de los pilares en el control de los eventos tromboembólicos. Los medicamentos biológicos se asocian al control rápido del cuadro inflamatorio, sin embargo, siempre se discute el tema de seguridad para la reactivación de infecciones latentes, en particular tuberculosis. Presentamos el caso de un paciente de 37 años que debutó con trombosis venosa profunda en el miembro inferior izquierdo y posteriormente con tromboembolismo pulmonar masivo. Luego de investigar la etiología y ampliar la historia clínica se le diagnosticó Enfermedad de Crohn (EC). Al realizar los estudios previos al uso de biológicos, las pruebas de PPD y quantiferon resultaron positivas, luego de la discusión del caso se decidió iniciar tratamiento con ustekinumab.

Inflammatory bowel disease (IBD) is a spectrum of chronic immune-mediated diseases that affect the gastrointestinal tract and other extraintestinal systems, behaving as a systemic disease. Thromboembolic phenomena are a frequent complication in IBD, because of hypercoagulability states associated with disease activity, and their presence has a negative impact on prognosis and patient survival. Due to this, the control of the inflammatory activity of IBD is one of the pillars in the control of thromboembolic events. Biological drugs are associated with rapid control of the inflammatory process, however, the security profile for the reactivation of latent infections, particularly tuberculosis, is always discussed. We present the case of a 37-year-old patient who presented with deep vein thrombosis in the left lower limb and later with massive pulmonary thromboembolism. During his evaluation, he was diagnosed with Crohn's disease (CD). When carrying out the studies prior to the use of biologics, PPD and quantiferon tests were positive. After discussing the case, we decided to start treatment with ustekinumab.

Signal detection and analysis of the adverse events of ustekinumab based on OpenFDA database / 中国药房

OBJECTIVE To analyze the risk of adverse drug reaction of ustekinumab， so as to provide reference for rational drug use in clinic. METHODS The adverse events （AE） reports related to ustekinumab included in the FDA public data program （OpenFDA） database were analyzed after marketing （from September 25th 2009 to December 30th 2021）. The risk signals were mined for top 100 AE by the method of reporting odds ratio （ROR） and proportional reporting ratio （PRR）. RESULTS A total of 62 356 AE reports related to ustekinumab were retrieved， male patients （51.79%） were more than female patients （39.51%）. Results of ROR method and PRR method showed that 31 suspicious signals were mined， mainly infections and infectious diseases （9 kinds）， general disorders and administration site conditions （5 kinds）， skin and subcutaneous tissue disorders diseases （4 kinds）， musculoskeletal and connective tissue disorders （4 kinds）， etc. Fourteen suspicious signals were not included in the instructions， such as hepatic enzyme increase， basal cell carcinoma， pericarditis， pemphigus， hair loss， synovitis， glossodynia， etc. CONCLUSIONS During clinical dosing of ustekinumab， in addition to ADR mentioned in package inserts， great attention should be paid to the patient’s liver function， skin status， hair loss and cardiovascular-related risks，which is helpful to discover AE early and ensure the safety medication of patients.

Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore

INTRODUCTION@#Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis.@*METHODS@#This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16.@*RESULTS@#A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years.@*CONCLUSION@#Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

Ustequinumabe no manejo da doença de Crohn: um estudo observacional brasileiro / Ustekinumab in crohn's disease management: a brazilian observational study

ABSTRACT Background: Real-world data on the use of Ustekinumab (UST) in Brazilian and Latin American patients with Crohn's disease (CD) are scarce. Objective: The primary endpoint was assessment of clinical remission at weeks 8 and 52, and secondary endpoints were: assessment of clinical response at weeks 8 and 52, endoscopic remission, adverse events, and rates of CD-related abdominal surgery during follow-up. Methods: observational and retrospective study, including patients with CD treated at two centers, who received UST at any time during their treatment. Remission and clinical response were defined as a Harvey-Bradshaw index ≤4 and ≥3 points reduction, respectively. Results: Seventy-four patients were included, 85.1% previously exposed to anti-TNFs. Clinical remission was observed in 45.8% and 59.4% of patients at weeks 8 and 52, respectively. The clinical response rates were 54.2% and 67.6% at weeks 8 and 52. Endoscopic remission was observed in 21.8% of patients. Seventeen patients had adverse events, mostly mild infections, with 22.9% of patients undergoing abdominal surgery (ileocolectomy being the most common procedure). Conclusion UST therapy resulted in significant rates of remission and clinical response, as described in other real-world studies. Few patients had adverse events during treatment, showing its adequate safety profile.

RESUMO Contexto: Dados de vida real sobre o uso de Ustequinumabe (UST) em pacientes brasileiros e latino-americanos com doença de Crohn (DC) são escassos. Objetivo: O desfecho primário foi a avaliação da remissão clínica nas semanas 8 e 52, e os desfechos secundários foram: avaliação da resposta clínica nas semanas 8 e 52, remissão endoscópica, eventos adversos e taxas de cirurgia abdominal relacionada à DC durante o seguimento. Métodos: Estudo observacional e retrospectivo, incluindo pacientes com DC tratados em dois centros, que receberam UST em qualquer momento do tratamento. A remissão e a resposta clínica foram definidas como índice de Harvey-Bradshaw ≤4 e ≥3 pontos de redução, respectivamente. Resultados: Foram incluídos 74 pacientes, 85,1% previamente expostos a anti-TNFs. A remissão clínica foi observada em 45,8% e 59,4% dos pacientes nas semanas 8 e 52, respectivamente. As taxas de resposta clínica foram de 54,2% e 67,6% nas semanas 8 e 52. A remissão endoscópica foi observada em 21,8% dos pacientes. Dezessete pacientes apresentaram eventos adversos, principalmente infecções leves, sendo 22,9% dos pacientes submetidos à cirurgia abdominal (sendo a ileocolectomia o procedimento mais comum). Conclusão: A terapia com UST resultou em taxas significativas de remissão e resposta clínica, conforme descrito em outros estudos do mundo real. Poucos pacientes apresentaram eventos adversos durante o tratamento, mostrando seu adequado perfil de segurança.

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.

Psoriasis paradójica palmoplantar secundaria al tratamiento de la colitis ulcerosa con adalimumab / Paradoxical psoriasis of the palms and soles due to treatment of ulcerative colitis with adalimumab

Los anticuerpos anti-TNF-a (tumor necrosis factor alpha) se utilizan para tratar tanto la psoriasis como la enfermedad inflamatoria intestinal (EII). Sin embargo, estos fármacos han sido implicados en la ocurrencia de la psoriasis paradójica en los pacientes sin antecedentes de psoriasis que reciben tratamiento por una colitis ulcerosa (CU) y otras enfermedades autoinmunes. Se presenta el caso de un paciente de 29 años, sin antecedentes de dermatosis, que desarrolló una psoriasis palmoplantar paradójica por el uso del adalimumab que recibía por un diagnóstico de CU. El cuadro remitió al suspender el medicamento y recurrió al reiniciarlo, motivo por el cual se rotó al ustekinumab. La CU respondió satisfactoriamente, sin nuevas lesiones dermatológicas.

Anti TNF-a (tumor necrosis factor alpha) antibodies are used to treat both psoriasis and inflammatory bowel disease (IBD). However, these drugs have been implicated in the occurrence of the so-called paradoxical psoriasis in patients with no previous history of psoriasis, who receive treatment for ulcerative colitis and other autoimmune diseases. We present a 29-year-old male patient, with no previous history of dermatosis, who developed paradoxical palmar-plantar psoriasis due to the use of adalimumab that he was receiving for a diagnosis of ulcerative colitis. The condition remitted when the drug was suspended and recurred when it was restarted, and for that reason, treatment was rotated to ustekinumab. Ulcerative colitis responded satisfactorily, with no new dermatological lesions.

Recalcitrant Pityriasis Rubra Pilaris Treated with Ustekinumab / 대한피부과학회지

No abstract available.

Ustekinumab is effective in biological refractory Crohn's disease patients–regardless of approval study selection criteria

BACKGROUND/AIMS: Ustekinumab is effective in active Crohn's disease. In a retrospective study, we assessed the clinical outcome in nonresponders to anti-tumor necrosis factor therapy, and/or conventional therapy and/or the α4β7-integrin inhibitor vedolizumab. As approval study populations do not always reflect the average “real world” patient cohort, we assessed weather patients who would not have qualified for approval studies show similar outcomes. METHODS: Forty-one patients with mild to severe active Crohn's disease were treated with ustekinumab (intravenous 6 mg per kg/body weight) followed by subcutaneous ustekinumab (90 mg) at week 8. Depending on the clinical response maintenance therapy was chosen every 8 or 12 weeks. Clinical response was defined by Crohn's Disease Activity Index (CDAI) decline, decline of stool frequency or clinical improvement. Inclusion criteria for approval studies were assessed. RESULTS: The 58.5% (24/41) showed clinical response to ustekinumab. The 58.3% of this group (14/24) achieved clinical remission. Clinical response correlated significantly with drop of stool frequency and improvement of CDAI score. The 39 out of 41 patients had no side effects and we observed no serious infections. About a third of our patients would not have met ustekinumab approval study criteria. However, patients who did not meet study criteria showed clinical improvement numerically in the same range compared to patients who would have qualified for approval studies. CONCLUSIONS: Ustekinumab is effective, safe and well tolerated in a highly therapy refractory patient cohort. Even though a reasonable number of patients did not meet ustekinumab approval study criteria, approval study results seem to be representative to the overall patient cohort.

Treatment Outcomes and Response Pattern of Ustekinumab in Korean Patients with Psoriasis: A Retrospective Single-center Study / 대한피부과학회지

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease affecting 2~3% of the worldwide population. Ustekinumab, an IL-12/23p40 inhibitor, is a biologic reported to be effective and safe in treating psoriasis. However, there are limited data on the treatment outcomes of ustekinumab in patients with psoriasis in Korea. OBJECTIVE: To evaluate the treatment outcomes and response pattern of ustekinumab in patients with psoriasis in Korea. METHODS: This was a retrospective single-center study. Eighty-four patients with psoriasis treated with ustekinumab were analyzed. Each patient's medical records, psoriasis area and severity index (PASI) score, and body surface area were reviewed at baseline and up to week 52. RESULTS: A total of 84 patients were included (male:female=1.8:1). The mean age was 44.5 years. At week 16, 86.7% achieved PASI75, 59.0% achieved PASI90, and 20.5% achieved PASI100. By week 16, 84.8% of subjects had attained PASI75 for the head region, whereas 79.0% had attained it for the lower extremities, indicating a relatively slower treatment response of psoriatic lesions on the lower extremities. Four patients discontinued treatment due to lack of effect. No severe adverse events occurred during the follow-up period. CONCLUSION: Ustekinumab demonstrated highly effective and safe treatment profiles in Korean psoriatic patients, consistent with the previous reports from mainly Western countries. Psoriasis severity and treatment responsiveness may vary with body region.

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.

Economic Factors as Major Determinants of Ustekinumab Drug Survival of Patients with Chronic Plaque Psoriasis in Korea

BACKGROUND: Drug survival, defined as the time until discontinuation, is a parameter reflecting real-world therapeutic effectiveness. Few studies have examined the influence of economic factors on the drug survival of biologic agents for psoriasis, particularly in Asian countries. OBJECTIVE: To determine the drug survival for ustekinumab in real-life settings and investigate the factors affecting drug survival for psoriasis patients in Korea. METHODS: We evaluated 98 psoriasis patients who were treated with ustekinumab at a single center. We analyzed the efficacy and drug survival of ustekinumab. Cox proportional hazard analysis and competing risk regression analysis were performed to reveal the factors affecting the drug survival of ustekinumab. RESULTS: The overall mean drug survival was 1,596 days (95% confidence interval [CI], 904~2,288). Among the 39 cessations of ustekinumab treatment, 9 (23.1%) patients discontinued treatment after experiencing satisfactory results. Multivariate Cox proportional hazard analysis revealed that paying on patients' own expense was the major predictor for the discontinuation of ustekinumab (hazard ratio [HR], 9.696; 95% CI, 4.088~22.998). Competing risk regression analysis modeling of discontinuation because of factors other than satisfaction of an event also revealed that ustekinumab treatment at the patient's expense (HR, 4.138; 95% CI, 1.684~10.168) was a predictor of discontinuation rather than satisfaction. CONCLUSION: The results of our study revealed that the cost of biologics treatment affects the drug survival of ustekinumab and suggested that economic factors affect the drug survival of ustekinumab treatment in Korea.

A Case of Paradoxical Flare of Pustular Psoriasis after Ustekinumab Therapy / 대한피부과학회지

Biologics are the most advanced treatment for psoriasis. Ustekinumab, one of the biologics for psoriasis, is a human monoclonal antibody that binds to the p40 subunit of interleukin-12 and interleukin-23. A 41-year-old woman with a 17-year history of plaque psoriasis and psoriatic arthritis presented with worsening lesions. The patient had previously been treated with a number of topical and systemic medications and narrow band ultraviolet B. However, none of the treatments consistently controlled her disease. Thus, treatment with ustekinumab 45 mg via subcutaneous injection was initiated. Approximately 7 days after the first treatment, she experienced a flare with generalized pustules in her whole body. The condition was controlled with systemic steroid treatment. The patient was subsequently treated with adalimumab, and improvement in her plaque and pustular lesions was noted. Herein, we report a case of psoriasis that flared up after ustekinumab therapy, which was accompanied by a morphological change from plaque to pustular lesions.

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Economic Burden Can Be the Major Determining Factor Resulting in Short-Term Intermittent and Repetitive Ustekinumab Treatment for Moderate-to-Severe Psoriasis

BACKGROUND: The continuous use of biologic agents in the treatment of psoriasis has been reported to result in successful and sustained therapeutic effects and safety. However, some patients choose intermittent and repetitive treatment. OBJECTIVE: To determine the factors for selecting intermittent and repetitive ustekinumab treatment for the management of psoriasis. METHODS: From January 2011 to October 2016, we enrolled 30 psoriasis patients who discontinued ustekinumab treatment and were followed up for psoriasis treatment. We reviewed data regarding patients' clinical characteristics and the treatment they received, and investigated the factors for selecting intermittent treatment. RESULTS: A total of 52 ustekinumab treatment periods were administered to the 30 patients. Of the 52 treatment periods, 34.6% were covered by insurance and 82.4% were discontinued after sufficient improvement had been made or at the patient's request. Further analysis comparing the first and second ustekinumab treatments revealed that the patients who used ustekinumab in second treatment were more likely to be insured. In addition, the rate of patients reaching psoriasis area and severity index (PASI)75 and PASI90 was similar between the first and subsequent ustekinumab treatments. CONCLUSION: We found that the patients who used ustekinumab intermittently were those who were satisfied with the outcome of ustekinumab treatment but could not afford the treatment. These results suggested that economic burden can be a factor for the patients' choice of short-term intermittent treatment. The expansion of insurance coverage can increase the effectiveness of, and patients' satisfaction with, the management of psoriasis.

Emerging Therapies: What Are Promising in the Near Future? / 대한소화기학회지

The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective. Additionally, vedolizumab can be used in patients already failed an anti-TNF therapy. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to use in medically-refractory Crohn's disease especially as a second line drug. Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that they are given orally instead of parenterally. Early results showed that patients with moderately to severely active ulcerative colitis receiving tofacitinib were more likely to achieve remission at 8 weeks than those receiving placebo. However, these results have not been as robust in Crohn's disease. Much of the positioning will depend on the safety profile such as opportunistic infection and atherogenic risk. The challenges for the future are to determine the therapeutic drug monitoring-guided dose optimization, optimal timing and drug combinations to produce the most effective, and safest outcomes for IBD patients.

Squamous Cell Carcinoma Associated with Arsenic Keratosis in a Psoriasis Patient Treated with Ustekinumab: A Case Report / 대한피부과학회지

A 53-year-old Korean woman with known history of psoriasis and treatment with ustekinumab over 16 months, presented with a nontender erythematous plaque with oozing noted on her left sole. Histopathologic examination of the lesion confirmed squamous cell carcinoma (SCC). Although use of ustekinumab was considered a possible risk factor for the development of SCC, administration of ustekinumab was continued per her request following an operation for removal of the SCC. And 19 months later, newly developed multiple hyperkeratotic papules on her soles were diagnosed as arsenic keratosis based on her past history of consumption of Chinese traditional herbal medicine. I concluded that SCC in this patient was not caused by ustekinumab, but was associated with arsenic keratosis. This case emphasizes that screening for risk factors associated with skin malignancies, such as exposure to arsenic or presence of arsenic keratosis, should be performed prior to using biologics in Korean psoriasis patients.

The Effect of Combination Treatment with Ustekinumab and Topical Agents in Korean Patients with Moderate-to-severe Psoriasis: A Retrospective Study of 30 Patients through 5 Years of Follow Up / 대한피부과학회지

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder affecting approximately 1~3% of the general population. Ustekinumab is a recently developed human monoclonal antibody for psoriasis that binds to the p40 subunit shared by the interleukins IL-12 and IL-23. OBJECTIVE: The purpose of this study was to evaluate the effect of combination treatment with ustekinumab and topical agents in 30 Korean patients with psoriasis regarding different clinical parameters. METHODS: We retrospectively searched to identify patients with moderate-to-severe plaque-type psoriasis who had initiated treatment with ustekinumab between January 2012 and January 2016. Among them, our study was conducted in 30 patients with psoriasis who were treated with ustekinumab and topical agents for at least 16 weeks by analyzing their clinical charts and photographs. RESULTS: Overall, 16.7%, 93.3%, and 96.2% patients achieved PASI 75 response rates at weeks 4, 16, and 40, respectively. Furthermore, fifteen patients achieved 90% improvement in their PASI score at 100 weeks and five patients maintained their PASI score at 160 weeks. The efficacy of treatment with ustekinumab was different in sub-group analysis. Non-smokers enjoyed a higher therapeutic effect than did smokers. In addition, the therapeutic effect of ustekinumab was lower in the groups with psoriatic arthritis and nail psoriasis. However, it was not statistically significant. None of the patients experienced serious adverse events requiring the interruption of treatment. CONCLUSION: Combination treatment with ustekinumab and topical agents provides effective treatment results for Korean patients with psoriasis.

Efficacy and safety of ustekinumab in Japanese patients with moderately to severely active Crohn's disease: a subpopulation analysis of phase 3 induction and maintenance studies

BACKGROUND/AIMS: Efficacy and safety of ustekinumab were evaluated in a Japanese subpopulation with moderately to severely active Crohn's disease (CD) in UNITI-1, UNITI-2 and IM-UNITI studies and results were compared with the overall population. METHODS: Overall, patients in UNITI-1 (Japan, n=56; failed response to tumor necrosis factor antagonist) and UNITI-2 (Japan, n=26; failed response to prior conventional therapy) were randomized to placebo or ustekinumab intravenous induction (130 mg or ~6 mg/kg) at week 0. Responders to ustekinumab induction therapy (Japan, n=21) were randomized to placebo or ustekinumab (90 mg, subcutaneous) maintenance (every 12 weeks [q12w] or 8 weeks [q8w]) in IM-UNITI. The primary endpoint was clinical response at week 6 for induction studies and clinical remission at week 44 for maintenance study. RESULTS: Percentage of patients achieving clinical response at week 6 was greater in ustekinumab 130 mg and ~6 mg/kg groups than in the placebo group (UNITI-1: 36.8% and 31.6% vs. 27.8%, respectively, for Japanese; 34.3% and 33.7% vs. 21.5%, respectively, for overall; UNITI-2: 37.5% and 55.6% vs. 11.1%, respectively, for Japanese; 51.7% and 55.5% vs. 28.7%, respectively, for overall). Clinical remission rate at week 44 during maintenance was greater in the ustekinumab 90 mg SC q12w and q8w groups than in the placebo group (50.0% and 55.6% vs. 25.0%, respectively, for Japanese; 48.8% and 53.1% vs. 35.9%, respectively, for overall). Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. CONCLUSIONS: Ustekinumab could be considered as a new therapeutic option for moderately to severely active CD in Japanese patients. Both ustekinumab induction and maintenance treatments were generally well tolerated (Clinical Trial Registration: NCT01369329, NCT01369342, NCT01369355).

Análise de custo por resposta dos medicamentos biológicos no tratamento da psoríase moderada a grave sob as perspectivas dos sistemas de saúde público e privado, no Brasil / Cost per responder analysis of biologic drugs for the treatment of moderate to severe psoriasis under Brazilian public and private healthcare systems perspectives

Objetivo: Estimar o custo por resposta dos medicamentos biológicos no tratamento da psoríase moderada a grave sob as perspectivas do Sistema de Saúde Suplementar (SSS) e Sistema Único de Saúde (SUS), representado pela Secretaria de Estado da Saúde de São Paulo, no Brasil. Métodos: Quatro medicamentos biológicos foram considerados na análise: adalimumabe, etanercepte, infliximabe e ustequinumabe. Os dados de eficácia foram obtidos de uma metanálise publicada, que avaliou a resposta PASI 75 dos medicamentos na semana 24 de tratamento. O custo do tratamento foi obtido considerando o preço de aquisição dos medicamentos, conforme perspectiva analisada, e a posologia preconizada na bula de cada um deles. Análise de sensibilidade foi conduzida a fim de avaliar o impacto das incertezas nos resultados encontrados. Resultados: A análise mostrou que, sob a perspectiva do SSS, ustequinumabe apresentou o menor custo por resposta PASI 75 (R$ 66.371) por ano de tratamento, seguido por infliximabe (R$ 139.605), adalimumabe (R$ 152.501) e etanercepte (R$ 179.812). Resultado semelhante foi observado na perspectiva do SUS, no qual ustequinumabe apresentou custo por resposta PASI 75 de R$ 47.229, seguido por infliximabe (R$ 75.145), adalimumabe (R$ 90.292) e etanercepte (R$ 130.523). Ajuste de dose para ustequinumabe mostrou ser o parâmetro mais sensível na análise de sensibilidade. Conclusão: Avaliações econômicas são ferramentas importantes para auxiliar gestores de saúde no processo de tomada decisão. A presente análise mostrou que, dentre as alternativas comparadas, ustequinumabe é o medicamento biológico que apresenta o menor custo por resposta PASI 75 (mais custo-efetivo), independentemente da perspectiva analisada (público ou privado).

Objective: To estimate the cost per responder of biologic drugs in moderate to severe psoriasis treatment from the private and public (State Health Secretariat of São Paulo) perspectives in Brazil. Methods: Four biologic drugs were considered in the analysis: adalimumab, etanercept, infliximab and ustekinumab. Efficacy data was obtained from a published metanalysis, which evaluated PASI 75 response after treatment with biologic drugs after 24 weeks of treatment. The cost of treatment was obtained considering drug acquisition cost, according to the analyzed perspective, and dosage according to each drug information label. Sensitivity analysis was performed to evaluate the impact of uncertainty in the results. Results: The analysis demonstrated that, from the private perspective, ustekinumab presented lower cost per PASI 75 response (R$ 66,371), in one year of treatment, followed by infliximab (R$ 139,605), adalimumab (R$ 152,501), and etanercept (R$179,812). Similar results were found from public perspective, with ustekinumab presenting a cost per PASI 75 response of R$ 47,229 per year of treatment, followed by infliximab (R$ 75,145), adalimumab (R$ 90,292) and etanercept (R$ 130,523). Dose adjustment for ustekinumab was shown to be the most sensitive parameter in the sensitivity analysis. Conclusion: Economic evaluations are important tools to support payers during the decision making process. The current analysis demonstrated that, among compared options, ustekinumab is the biologic with the lowest cost per PASI 75 responder (more cost-effective), regardless the perspective considered (public or private).