RESUMO

Background: Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC. Methods: We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results: A total of 50 patients were included (female, n = 36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n = 31; vedolizumab [VDZ], n = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs. Conclusions: In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

RESUMO

ABSTRACT Objective Therefore, this study aimed to evaluate the impact of secukinumab and ustekinumab against moderate-to-severe plaque psoriasis in a Brazilian pediatric population with access to public healthcare. Methods A survey of immunobiological treatments registered for use against pediatric psoriasis at the National Health Surveillance Agency was conducted. These treatments were compared to the list available in the same treatment category in the public health system through the Clinical Protocol and Therapeutic Guidelines for psoriasis. A quantitative analysis of the data of patients treated with immunobiological drugs the previous year in accordance with the Clinical Protocol and Therapeutic Guidelines was performed using data available in the DATASUS portal. Results The public budget impact scenarios analyzed were comparable to the investment already planned for acquiring the only available drug option. Conclusion The incorporation of two therapeutic options in the Clinical Protocol and Therapeutic Guidelines list for moderate-to-severe pediatric psoriasis was feasible in a horizon of 5 years compared to the investment into the single option available to pediatric patients. These findings can facilitate the local analysis of budgetary impact and discussions on the feasibility of this therapeutic incorporation at the state level.

RESUMO

A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease was attended in the Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to the failure of other treatments (phototherapy, oral acitretin) for psoriasis and a Psoriasis Area Severity Index >10. We evaluated the impact of treatment with ustekinumab on severe infectious diseases in a patient with uncontrolled psoriasis and LOCID followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, cultures of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation; pathogenic variants in genetic sequencing, and clinically significant variants in the whole exome for primary immunodeficiencies were not detected. The main infections before and after treatment with ustekinumab were chronic sinusitis and gastroenteritis. The patient was infected with COVID-19, dengue (twice) and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence the susceptibility of the patient with LOCID to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease.

RESUMO

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.

RESUMO

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.

RESUMO

This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn's disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.

RESUMO

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.

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.

Assuntos

RESUMO

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.

RESUMO

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

Assuntos

RESUMO

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.

Assuntos

RESUMO

BACKGROUND: In the last decade, new therapies with different mechanisms of action have been approved for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). Due to the lack of comparative head-to-head trials, the ideal positioning of agents as the most appropriate first- or second-line therapies remains to be defined. OBJECTIVE: This survey aimed to evaluate the perception and decisions of Brazilian Inflammatory Bowel Diseases (IBD) specialists in positioning of new therapies (vedolizumab [VEDO], ustekinumab [UST] and tofacitinib [TOFA]) in the management of IBD in different clinical scenarios. METHODOLOGY: An anonymous national web-based questionnaire was used to determine the positioning of treatment options in different clinical scenarios (using Google Forms platform), which involved different age ranges, phenotypes, clinical situations and previous exposure to anti-TNF agents (14 scenarios for CD and 10 scenarios for UC). In CD, physicians could choose between UST or VEDO, whilst in UC, between UST, VEDO or TOFA. Six reasons for the specific choice were proposed, such as mechanism of action, safety, method of administration or onset of action. Statistical analysis was carried out with chi-square and t-tests. RESULTS: A total of 150 out of 672 GEDIIB IBD specialists (22.32%) responded to the survey. In CD scenarios, UST was the most dominant choice (11/14 scenarios), with VEDO dominating only 3 clinical situations. In UC scenarios, VEDO was the dominant choice (8/10), with UST being chosen for scenarios that included extraintestinal manifestations. Among the reasons for specific choices, the most commonly chosen were the higher efficacy due to the intrinsic mechanism of action and safety profile. CONCLUSIONS: UST was the dominant choice as compared to VEDO in CD in most scenarios, especially due to its mechanism of action and safety. VEDO was the dominant choice as compared to UST and TOFA in UC scenarios, mainly for reasons also related to its mechanism of action and safety profile. Comparative studies including patient outcomes are needed to better define the positioning of new IBD therapeutic options in our country.

Assuntos

RESUMO

Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn's disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.

RESUMO

CARD14-associated papulosquamous eruption (CAPE) is a proposed term that encompasses features ranging from psoriasis to pityriasis rubra pilaris (PRP) in association with CARD14 mutations. The early onset of the disease, prominent facial involvement, family history of an autosomal dominant trait, and poor response to conventional treatment are characteristics of CAPE that distinguish it from classical psoriasis and PRP. We describe the clinical features, family history, and response to therapy in three unrelated children with CAPE and compare these characteristics with those of previously described pediatric patients. Testing for CARD14 mutations in children with early onset of features of psoriasis or pityriasis rubra pilaris and resistance to conventional therapy should be considered.

Assuntos

RESUMO

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.

Assuntos

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic and incurable entity. Therapy with anti-TNF-α agents was the first biologic therapy approved in Mexico for IBD. New biologic agents, such as vedolizumab and ustekinumab, have recently been added, as have small-molecule inhibitors. AIM: To update the biologic therapeutic approach to IBD in Mexico with new anti-TNF-α agents and novel biologics whose mechanisms of action induce and maintain remission of Crohn's disease and ulcerative colitis (UC). MATERIALS AND METHODS: Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned to participate. The consensus was divided into 3 modules, with 49 statements. The Delphi method was applied, sending the statements to all participants to be analyzed and edited, before the face-to-face meeting. During said meeting, the clinical studies were shown, emphasizing the level of clinical evidence, and the final discussion and voting round on the level of agreement of all the statements was conducted. RESULTS: In this second Mexican consensus, recommendations are made for new anti-TNF-α agents, such as golimumab, new biologics with other mechanisms of action, such as vedolizumab and ustekinumab, as well as for the small-molecule inhibitor, tofacitinib. CONCLUSIONS: The updated recommendations focus on patient-reported outcomes, biologic therapy, small-molecule inhibitors, and the safety aspects of each of the drugs.

RESUMO

Despite significant advances in medical therapy in the management of Crohn's disease (CD), surgery is still required in a significant proportion of patients and constitutes an important tool in treatment algorithms. Recently, more options of biological agents have been made available, and most patients with CD undergoing surgical procedures have been previously exposed to this class of drugs. There is controversy in the literature as to whether anti-tumor necrosis factor (TNF) agents, anti-integrins, or anti-interleukins (ILs) have a direct relationship with increased postoperative complications. In this narrative review, the authors summarize the most important data regarding the effect of biologics on postoperative outcomes in CD. Most studies (with different designs) are based on the experience with anti-TNF agents, mostly with infliximab. Some studies outlined the relationship between vedolizumab and postoperative complications, and there is a lack of data with ustekinumab in this scenario. Most studies are retrospective, but few prospective data are available. A cause-effect (proof of concept) direct relationship between biologics and an increase in postoperative morbidity has not been demonstrated to date. Several confounding factors such as previous use of steroids, malnutrition, and unfavorable abdominal conditions have a definitely effect on postoperative complications in CD. Biologics seem safe to be used in the perioperative period, but available data are still controversial. Multidisciplinary individualized decisions should be made on a case-to-case basis, adapting the surgical strategy according to risk factors involved.

RESUMO

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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

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).

Assuntos