Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and ?-catenin in colonic mucosa without fecal stream.

PURPOSE: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. METHODS: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. RESULTS: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. CONCLUSIONS: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Perioperative nutritional optimization in inflammatory bowel diseases: when and how?

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are commonly associated with important changes in nutritional status (NS). Both malnutrition and obesity have a negative impact on the course of both diseases, with greater risks of postoperative complications, such as anastomotic dehiscences, reoperations, prolonged hospitalizations, and increased mortality. The diagnostic criteria for identifying individuals at nutritional risk, with clear indication for preoperative nutritional therapy, involves several factors. Oral nutrition should be the first choice of nutritional support. If the patient has difficulty in consuming food, the enteral route is the second option, through elementary (amino acids), semi-elementary (oligopeptides), or polymeric (whole proteins) formulas. When oral or enteral routes are not indicated (in the presence of intestinal obstruction or ischemia, fistula, or bleeding), total parenteral nutrition can meet the daily nutritional needs of the critically ill patient. Nutritional support can be performed exclusively or in an associated way, which will depend on the nutritional severity of the patient with IBD. Nutritional screening should be performed at all stages of the disease, always individually and with professionals with experience in IBD. The reduction of complications in the perioperative period is not only associated with adequate surgical technique, but also with adequate nutritional support and clinical preparation before surgery. Therefore, the dietitian with a focus in IBD has an important role in the multidisciplinary team, collaborating with all stages of treatment and with the optimization of the nutritional status of the surgical patient. (AU)

Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and Β-catenin in colonic mucosa without fecal stream

ABSTRACT Purpose: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. Methods: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. Results: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. Conclusions: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Optimizing biologic therapy in IBD: how essential is therapeutic drug monitoring?

Proposed treatment targets for the management of inflammatory bowel disease (IBD) have moved beyond symptomatic improvement towards more objective end points, such as healing of the intestinal mucosa. This treat-to-target approach has been associated with improved disease outcomes such as diminished bowel damage, surgery and hospitalizations. Many patients with IBD require biologic therapy to achieve and maintain clinical and endoscopic remission, and antitumour necrosis factor antibodies remain the first-line biologic therapy in most areas of the world. Unfortunately, up to one-third of patients receiving this treatment are primary non-responders, and some patients that show an initial response can also lose response over time. Therapeutic drug monitoring (TDM) has been suggested as a useful tool to manage patients on antitumour necrosis factor treatment, including monitoring for dose escalation, de-escalation or to switch treatment. In this Perspective, we aim to summarize evidence and guidelines related to TDM in IBD management and also discuss potential strategies to optimize biologic treatment where TDM is not available.

BIOLOGICAL THERAPY PENETRATION FOR INFLAMMATORY BOWEL DISEASE IN LATIN AMERICA: CURRENT STATUS AND FUTURE CHALLENGES.

BACKGROUND: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients. OBJECTIVE: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America. METHODS: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries. RESULTS: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab). CONCLUSION: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.

Frequência de utilização da terapia biológica para doenças inflamatórias intestinais na América Latina: situação atual e desafios futuros / Biological therapy penetration for inflammatory bowel disease in latin america: current status and future challenges

ABSTRACT BACKGROUND: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients. OBJECTIVE: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America. METHODS: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries. RESULTS: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab). CONCLUSION: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.

RESUMO CONTEXTO: A introdução dos agentes anti-TNF representou um marco no tratamento da doença de Crohn (DC) e da recocolite ulcerativa (RCU), com maior eficácia e segurança quando comparado ao tratamento convencional. No entanto, ainda existem desafios significativos na América Latina para facilitar o acesso dos agentes biológicos a médicos e pacientes. OBJETIVO: O objetivo desta revisão foi reunir as evidências atuais sobre a penetração de agentes biológicos para DC e RCU na América Latina. MÉTODOS: Os dados são derivados de uma revisão sistemática previamente publicada que explorou diferentes características das doenças inflamatórias intestinais (DII) na América Latina. Os estudos incluídos nesta revisão sistemática anterior que continham descrições detalhadas da percentagem do uso de agentes biológicos em coortes de pacientes em diferentes países da América Latina e Caribe foram incluídos, e os achados descritivos foram compilados detalhando a penetração destes medicamentos no manejo das DII. RESULTADOS: Dos 61 estudos incluídos na revisão sistemática original, apenas 19 incluíram dados de percentagem de pacientes tratados com agentes biológicos. O uso de anti-TNF na DC variou de 1,51% no México até 46,9% na Colômbia, com a maioria dos estudos descrevendo o uso em aproximadamente 20%-40% dos pacientes na DC. Por outro lado, a frequência do uso de biológicos foi claramente menor na RCU, variando de 0% em 2009 a 16,2% em 2018, de acordo com dois estudos mexicanos. Apenas dois estudos descreveram a penetração de agentes anti-TNF nas DII em geral: 13,4% em estudo colombiano e 37,93% em outro estudo brasileiro. Nenhum estudo descreveu o percentual de uso de novos agentes biológicos (vedulizumabe e ustekinumabe). CONCLUSÃO: A penetração de agentes anti-TNF na América Latina é comparável ao resto do mundo na DC, mas menor na RCU. Com o aumento da incidência e prevalência de DII, estratégias específicas para se aumentar o acesso a agentes anti-TNF na RCU e novos agentes biológicos nas DII em geral são justificadas.

Impact of Preoperative Nutritional Status on the Incidence Rate of Surgical Complications in Patients With Inflammatory Bowel Disease With Vs Without Preoperative Biologic Therapy: A Case-Control Study.

OBJECTIVES: A case-control study was undertaken to assess the impact of preoperative nutrition on surgical outcomes in patients with inflammatory bowel disease with vs without preoperative biologic therapy. METHODS: Seventy patients who had received biologic therapy within 8 weeks before undergoing resection for active ulcerative colitis (n = 34) or Crohn's disease (n = 36) were included (BIO group). The control group comprised 70 patients without exposure to biologics, selected based on 5 matching criteria: inflammatory bowel disease subtype (ulcerative colitis/Crohn's disease), age (≤ or >40 years), disease severity (moderate/severe), surgical approach (open/laparoscopic), and main surgical procedure. Poor nutrition was defined as the presence of at least one of the following criteria: weight loss >10%-15% within 6 months, body mass index <18.5 kg/m, Subjective Global Assessment Grade C, or serum albumin <30 g/L. RESULTS: The proportion of patients with preoperative poor nutrition was 43% in the BIO and 33% in the control groups (P = 0.22). The incidence of postoperative infectious complications (anastomotic leak, intra-abdominal abscess, enterocutaneous fistula, or wound infection) was 16% in the BIO and 14% in the control groups (P = 0.81). In the BIO group, poor nutrition significantly increased the risk of infectious complications (27% vs 8% without poor nutrition, P = 0.03). In addition, in the control group, the incidence of infectious complications was higher in patients with poor nutrition, but not significantly (22% vs 11%, P = 0.21). DISCUSSION: Poor nutrition increases the risk of infectious complications after surgery. The detrimental effects of poor nutrition on postsurgical infection may be enhanced in patients who have received biologic therapy preoperatively.

Prevention of Postoperative Recurrence in CD: Tailoring Treatment to Patient Profile.

Crohn's disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts' score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.

Modern management of perianal fistulas in Crohn's disease: future directions.

Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

Economic impact of expanded use of biologic therapy for the treatment of rheumatoid arthritis and Crohn's disease in Argentina, Brazil, Colombia, and Mexico.

OBJECTIVES: To estimate economic impact resulting from increased biologics use for treatment of rheumatoid arthritis (RA) and Crohn's disease (CD) in Argentina, Brazil, Colombia, and Mexico. METHODS: The influence of increasing biologics use for treatment of RA during 2012-2022 and for treatment of CD during 2013-2023 was modeled from a societal perspective. The economic model incorporated current and projected medical, indirect, and drug costs and epidemiologic and economic factors. Costs associated with expanded biologics use for RA were compared with non-expanded use in Argentina, Brazil, Colombia, and Mexico. A similar analysis was conducted for CD in Brazil, Colombia, and Mexico. RESULTS: Accounting for additional costs of biologics and medical and indirect cost offsets, the model predicts that expanded use of biologics for patients with RA from 2012 to 2022 will result in cumulative net cost savings of ARS$2.351 billion in Argentina, R$9.004 billion in Brazil, COP$728.577 billion in Colombia, and MXN$18.02 billion in Mexico; expanded use of biologics for patients with CD from 2013 to 2023 will result in cumulative net cost savings for patients with CD of R$0.082 billion in Brazil, COP$502.74 billion in Colombia, and MXN$1.80 billion in Mexico. Indirect cost offsets associated with expanded biologics use were a key driver in reducing annual per-patient net costs for RA and CD. LIMITATIONS: Future economic projections are limited by the potential variance between projected and actual future values of biologic prices, wages, medical costs, and gross national product for each country. CONCLUSIONS: Increasing biologics use to treat RA and CD may limit cost growth over time by reducing medical and indirect costs. These findings may inform policy decisions regarding biologics use in Argentina, Brazil, Colombia, and Mexico.

Epidemiological profile of 175 patients with Crohn's disease submitted to biological therapy

INTRODUCTION: There is currently an increasing use of biological agents in the management of Crohn's disease (CD). There is lack of data regarding the epidemiological profile of patients on infliximab (IFX) and adalimumab (ADA) for CD in Brazil. OBJECTIVE: To identify the epidemiological characteristics of patients with CD who underwent biological therapy. METHOD: Retrospective multicenter study, with CD patients on biological therapy. Analyzed variables: gender, age at treatment initiation, Montreal classification, concomitant perianal disease and smoking status. RESULTS: 175 patients without previous exposure to biological agents were included, 93 (53%) were male. The mean age at treatment initiation was 35.5 (2-79) years old an the mean disease duration was 46.9 (0-480) months. Overall, 117 (66.9%) patients used IFX and 58 (33.1%), ADA. Montreal classification: age at diagnosis - A1 (n=21; 12%), A2 (n=102; 58.3%), and A3 (n=52; 29.7%). CD location - L1 (n=42; 24%), L2 (n=51; 29.1%), L3 (n=81; 46.3%), and L4 (n=1, 0.6%). Phenotype - B1 (n=59; 33.7%), B2 (n=46; 26.3%), and B3 (n=70; 40%). Perianal disease was found in 89 (50.9%) patients. CONCLUSIONS: The epidemiological profile of patients was similar to the literature. There was a high prevalence of patients with fistulizing CD. (AU)

INTRODUÇÃO: Atualmente há uso crescente dos agentes biológicos no manejo da doença de Crohn (DC). Há escassez de dados referentes ao perfil epidemiológico dos usuários de infliximabe (IFX) e adalimumabe (ADA) para DC no Brasil. OBJETIVO: Identificar as características epidemiológicas dos pacientes com DC submetidos à terapia biológica. MÉTODO: Estudo retrospectivo, multicêntrico, com portadores de DC que utilizaram terapia biológica. Variáveis analisadas: gênero, idade ao início do tratamento, classificação de Montreal, doença perianal concomitante e tabagismo. RESULTADOS: Foram incluídos 175 pacientes, sem exposição prévia a biológicos, sendo 93 (53%) homens. A média de idade no início do tratamento biológico foi de 35,5 (2-79) anos. O tempo médio de doença ao início do tratamento foi de 46,9 (0-480) meses. Do total da amostra, 117 (66,9%) utilizaram IFX e 58 (33,1%) ADA. Classificação de Montreal: idade ao diagnóstico - A1 (n=21; 12%), A2 (n=102; 58,3%) e A3 (n=52; 29,7%). Localização da DC - L1 (n=42; 24%), L2 (n=51; 29,1%), L3 (n=81; 46,3%) e L4 (n=1; 0,6%). Forma de apresentação - B1 (n=59; 33,7%), B2 (n=46; 26,3%) e B3 (n=70; 40%). Doença perianal foi encontrada em 89 (50,9%) dos pacientes. CONCLUSÕES: Os dados epidemiológicos dos pacientes foram compatíveis com os da literatura internacional. Houve uma alta prevalência de pacientes com a forma fistulizante da DC. (AU)

Biological therapy in the treatment of moderate-to-severe ulcerative colitis patients: can colectomy be prevented?

Ulcerative colitis treatment intends to induce remission, and its maintenance. Biological drugs, such as infliximab, have been indicated in moderate and severe cases of the disease, which are unresponsive to conventional medication. Randomized controlled trials proved the efficacy of biological treatment with high rates of sustained disease remission and mucosal healing. Recently, the concept of mucosal healing has been inversely associated with surgical treatment. Patients treated with infliximab have lower colectomy rates than those receiving conventional therapies. We suppose that earlier use of biological drugs in disease's course would lead to better clinical control and mucosal healing, with a consequent reduction in colectomy rates. To support this hypothesis, a literature review from January, 1996 to April, 2011 was performed. (AU)

O tratamento da colite ulcerativa tem como objetivo induzir a remissão, além da manutenção da remissão da doença. Agentes biológicos como o infliximabe têm sido indicados em casos moderados e graves da doença, os quais não respondem à medicação convencional. Ensaios clínicos randomizados comprovaram a eficácia do tratamento biológico com altas taxas de remissão da doença e cicatrização sustentada da mucosa. Recentemente, o conceito de cicatrização da mucosa tem sido inversamente associado com o tratamento cirúrgico. Pacientes tratados com infliximabe têm taxas mais baixas de colectomia se comparados com aqueles que receberam terapias convencionais. Supõe-se que quanto mais cedo for introduzida a terapia biológica no curso da doença, melhor seriam o controle clínico e a cicatrização da mucosa, com consequente redução nas taxas de colectomia. Para apoiar esta hipótese, foi realizada uma revisão da literatura entre janeiro de 1996 e abril de 2011. (AU)

Analysis of direct costs of anesthesia-related materials between spinal and venous anesthesia with propofol associated with local perianal block in hemorrhoidectomy

There is no consensus on the ideal anesthesia for hemorrhoidectomy in ambulatory facilities. Spinal anesthesia and venous propofol associated with local perianal block (combined anesthesia) are frequently used, and their direct costs may be crucial for the anesthesia type selection. The objective of this study was to compare the direct costs of anesthesia-related materials in hemorrhoidectomy between these two anesthetic techniques.Retrospective and cross-section analysis, comparing the direct costs of the materials of spinal and venous anesthesia with propofol associated with local perianal block, in hemorrhoidectomy. Twenty patients were included, ten submitted to each anesthesia type (five from each gender). The mean age in the spinal anesthesia group was 46.5 years and in the combined anesthesia group, 42.5 years (p=0.334). The mean cost of anesthesia-related materials was R$ 58.50 (R$ 36.48 - R$ 85.79) in the first group versus R$ 190.31 (R$ 98.16 - R$ 358.51) in the second - 69.27% difference between them (p<0.001). The mean costs according to gender analysis were R$ 50.32 and R$ 66.69 (p=0.263) in the spinal anesthesia group versus R$ 222.52 and R$ 158.10 (p=0.221) in the combined anesthesia group, respectively. The direct costs of anesthesia-related materials were significantly lower in patients submitted to hemorrhoidectomy using spinal anesthesia. No difference was observed between the genders in each group analyzed. (AU)

Não há consenso sobre a técnica anestésica de escolha para hemorroidectomias em regime ambulatorial. A raquianestesia e a anestesia combinada (venosa com propofol + local) são frequentemente utilizadas, e os custos das mesmas podem ser determinantes na escolha do melhor tipo de anestesia. O objetivo deste trabalho foi avaliar e comparar os custos diretos dos materiais anestésicos utilizados em hemorroidectomias entre essas duas técnicas. Foi feito um estudo retrospectivo e transversal, comparativo entre os custos diretos dos materiais anestésicos entre a raquianestesia e a anestesia venosa com poropofol associada ao bloqueio perianal local, em hemorroidectomias. Foram analisados 20 pacientes, 10 operados com cada técnica anestésica (5 de cada gênero). A média de idade do grupo da raquianestesia foi de 46,5 anos e do grupo da anestesia combinada foi de 42,5 anos (p=0,334). O custo médio do procedimento anestésico no primeiro grupo foi de R$ 58,50 (R$ 36,48 - R$ 85,79), no segundo foi de R$ 190,31 (R$ 98,16 - R$ 358,51). A diferença das médias foi de 69,27%, com significância estatística (p<0,001). A média dos custos dos gêneros masculino e feminino no grupo da raquianestesia foi de R$ 50,32 e R$ 66,69 (p=0,263) e no grupo da anestesia combinada foi de R$ 222,52 e R$ 158,10 (p=0,221), respectivamente. Os custos diretos médios dos materiais anestésicos dos pacientes submetidos a hemorroidectomias foram significativamente menores no grupo da raquianestesia. Não houve significância estatística na diferença entre os gêneros em cada grupo. (AU)

Reindução da remissão clínica com adalimumabe após interrupção do tratamento: uma alternativa no manejo da doença de Crohn / Re-induction of clinical remission with adalimumab after interruption of treatment: an alternative approach in Crohn´s disease management

Introdução: o Adalimumabe (ADA) é um anticorpo monoclonal totalmente humano, utilizado no tratamento da doença de Crohn (DC). Nos casos com necessidade de interrupção desta terapia, o resgate da resposta é controverso, e o papel da reindução da remissão com dose total de ataque pode ser uma alternativa nos casos graves da DC. Não há relatos desta forma de tratamento na literatura. O objetivo deste estudo foi relatar a experiência de dois pacientes tratados com reindução da remissão com ADA, após sua interrupção. Método: análise retrospectiva de dois casos submetidos a reindução em meio a uma coorte de 24 pacientes em uso de ADA para DC. Resultados: são descritos dois casos de pacientes jovens, em tratamento com ADA subcutâneo, que tiveram necessidade de interrupção da terapia (um por abscesso perineal extenso e outro por dificuldade de acesso ao fornecimento da medicação). Ambos foram tratados pela reindução com dose total de ataque do ADA, com bons resultados, sem efeitos adversos. Conclusão: não há na literatura estudos controlados que comparem a reindução com outras formas de resgate da terapia após a parada de qualquer agente anti-TNF. Experiências isoladas mostram bons resultados com esta alternativa terapêutica em casos graves e selecionados.

Introduction: Adalimumab (ADA) is a fully-human anti-TNF-alpha antibody approved for the management of Crohnïs disease (CD). In situations in which interruption of the treatment is mandatory, rescue therapy is controversial. Reinduction of remission with full dose may be an alternative in severe CD cases. There are no descriptions of this alternative in the literature. The aim of this study was to describe the experience with two patients treated with reinduction of remission with ADA, after interruption of treatment. Method: retrospective analysis of two patients in a cohort of 24 CD patients treated with ADA, with case reports. Results: description of two young patients with fistulizing CD, with the need of interruption of ADA therapy due to different reasons (perianal abscess and difficulties in receiving the medication). Both were treated with reinduction of remission with full dose ADA regimen (160/80 mg), with good results and no adverse events. Conclusions: there are no studies in the literature comparing reinduction of remission with other possibilities of rescue therapy after interruption of treatment with any anti-TNF agent. Small case series like this, show good results with this alternative in selected and severe cases of CD.

Análise de custo-minimização entre o Infliximabe (IFX) e o Adalimumabe (ADA) no tratamento da doença de Crohn (DC) / Cost-minimization analysis with Infliximab (IFX) and Adalimumab (ADA) for the treatment of Crohn's disease (CD)

INTRODUÇÃO: há uma preocupação crescente com os custos da terapia biológica no tratamento da DC. O objetivo deste estudo foi simular o custo-minimização do tratamento contínuo com o IFX e com o ADA em portadores de DC, num período de 1 ano, em variadas faixas de peso. MÉTODO: estudo farmacoeconômico de custo-minimização na simulação de tratamento com agentes biológicos de pacientes portadores de DC, com pesos diferentes. Os custos foram baseados no preço dos dois medicamentos isoladamente (IFX E ADA). RESULTADOS: o custo do tratamento com IFX (sistema público) foi de R$ 29.411,12 (entre 20 e 40 kg), R$ 44.116,68 (entre 41 e 60 kg), R$ 58.822,24 (entre 61 e 80 kg) e R$ 73.527,80 (entre 81 e 100 kg). O custo com ADA foi de R$ 52.045,16, independentemente do peso. A análise do sistema privado e situações de perda de resposta encontram-se descritas no artigo. CONCLUSÕES: houve menores custos com o uso do IFX abaixo de 60 kg, e com o ADA acima deste peso. Em simulação de perda de resposta ao IFX, houve menores custos absolutos com a troca para ADA do que aumento de dose do IFX, entre 40 e 100 kg.

INTRODUCTION: there are special concerns with costs of anti-TNF therapy in CD. The purpose of this study was a cost-minimization analysis with IFX and ADA in induction and maintenance of remission for one year, in different weight groups. METHOD: pharmacoeconomics simulation of cost-minimization in CD management. The total were based only in the drug costs in public and private health systems. Indirect findings such as infusion costs were not analyzed. RESULTS: the cost with IFX treatment for one year, in public system, was R$ 29.411,12 (between 20 and 40 kg), R$ 44.116,68 (between 41 and 60 kg), R$ 58.822,24 (between 61 and 80 kg) e R$ 73.527,80 (between 81 and 100 kg). The cost with ADA treatment was R$ 52.045,16, not related to weight differences. Private system and loss of response simulation findings are described in the article. CONCLUSIONS: there were lower costs with IFX below 60 kg, and with ADA above this specific weight. In loss of response to IFX situations, there were lower costs with changing to ADA strategy above 40 kg of weight.