Intestinal complications in patients with Crohn's disease in the Brazilian public healthcare system between 2011 and 2020.

BACKGROUND: This is a secondary database study using the Brazilian public healthcare system database. AIM: To describe intestinal complications (ICs) of patients in the Brazilian public healthcare system with Crohn's disease (CD) who initiated and either only received conventional therapy (CVT) or also initiated anti-tumor necrosis factor (anti-TNF) therapy between 2011 and 2020. METHODS: This study included patients with CD [international classification of diseases - 10th revision (ICD-10): K50.0, K50.1, or K50.8] (age: ≥ 18 years) with at least one claim of CVT (sulfasalazine, azathioprine, mesalazine, or methotrexate). IC was defined as a CD-related hospitalization, pre-defined procedure codes (from rectum or intestinal surgery groups), and/or associated disease (pre-defined ICD-10 codes), and overall (one or more type of ICs). RESULTS: In the 16809 patients with CD that met the inclusion criteria, the mean follow-up duration was 4.44 (2.37) years. In total, 14697 claims of ICs were found from 4633 patients. Over the 1- and 5-year of follow-up, 8.3% and 8.2% of the patients with CD, respectively, presented at least one IC, of which fistula (31%) and fistulotomy (48%) were the most commonly reported. The overall incidence rate (95%CI) of ICs was 6.8 (6.5-7.04) per 100 patient years for patients using only-CVT, and 9.2 (8.8-9.6) for patients with evidence of anti-TNF therapy. CONCLUSION: The outcomes highlighted an important and constant rate of ICs over time in all the CD populations assessed, especially in patients exposed to anti-TNF therapy. This outcome revealed insights into the real-world treatment and complications relevant to patients with CD and highlights that this disease remains a concern that may require additional treatment strategies in the Brazilian public healthcare system.

Intestinal complications in Brazilian patients with ulcerative colitis treated with conventional therapy between 2011 and 2020.

BACKGROUND: This was an observational, descriptive, and retrospective study from 2011 to 2020 from the Department of Informatics of the Brazilian Healthcare System database. AIM: To describe the intestinal complications (IC) of patients with ulcerative colitis (UC) who started conventional therapies in Brazil´s public Healthcare system. METHODS: Patients ≥ 18 years of age who had at least one claim related to UC 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) code and at least 2 claims for conventional therapies were included. IC was defined as at least one claim of: UC-related hospitalization, procedures code for rectum or intestinal surgeries, and/or associated disease defined by ICD-10 codes (malignant neoplasia of colon, stenosis, hemorrhage, ulcer and other rectum or anus disease, megacolon, functional diarrhea volvulus, intussusception and erythema nodosum). Descriptive statistics, annual incidence, and incidence rate (IR) [per 100 patient-years (PY)] over the available follow-up period were cal-culated. RESULTS: In total, 41229 UC patients were included (median age, 48 years; 65% women) and the median (interquartile range) follow-up period was 3.3 (1.8-5.3) years. Conventional therapy used during follow-up period included: mesalazine (87%), sulfasalazine (15%), azathioprine (16%) or methotrexate (1%) with a median duration of 1.9 (0.8-4.0) years. Overall IR of IC was 3.2 cases per 100 PY. Among the IC claims, 54% were related to associated diseases, 20% to procedures and 26% to hospitalizations. The overall annual incidence of IC was 2.9%, 2.6% and 2.5% in the first, second and third year after the first claim for therapy (index date), respectively. Over the first 3 years, the annual IR of UC-related hospitalizations ranged from 0.8% to 1.1%; associated diseases from 0.9% to 1.2% - in which anus or rectum disease, and malignant neoplasia of colon were the most frequently reported; and procedure events from 0.6% to 0.7%, being intestinal resection and polyp removal the most frequent ones. CONCLUSION: Study shows that UC patients under conventional therapy seem to present progression of disease developing some IC, which may have a negative impact on patients and the burden on the health system.

Prevalence, phenotype and medication for the pediatric inflammatory bowel disease population of a state in Southeastern Brazil.

BACKGROUND: Inflammatory bowel disease (IBD) can lead to social and economic impacts worldwide. In Brazil, where its adult prevalence is increasing, the epidemiology of the pediatric population is not well known, although there is a documented increase in pediatric IBD incidence worldwide. Brazil has continental dimensions, and Espírito Santo is a state of southeastern Brazil, the region with the highest demographic densities and is the economically most important in the country. AIM: To assess the prevalence, incidence, phenotype and medications in a Southeastern Brazilian pediatric population. METHODS: Data were retrieved from the Public Medication-Dispensing System of the Department of Health in Espírito Santo state from documentation required to have access to highly expensive medication from August 1, 2012 to July 31, 2014. There were 1048 registered patients with IBD of all ages, and of these patients, the cases ≤ 17 years were selected. The data were obtained through the analysis of administrative requests for these medications and included medical reports, endoscopy exams, histopathology and imaging tests, which followed the Clinical Protocols and Therapeutic Guidelines of the Brazilian Government. Only confirmed cases of IBD were included in the study. RESULTS: There were 55 pediatric patients/1048 registered patients (5.34%), with Crohn's disease (CD) representing 30/55 (55%), ulcerative colitis (UC) 24/55 (43.6%) and 1 unclassified IBD, a significant difference from adult patients (P = 0.004). The prevalence of IBD in pediatric patients was 5.02 cases/100.000 inhabitants; the incidence in 2014 was 1.36 cases/100.000 inhabitants. The mean age at diagnosis was 12.2 years (± 4.2). There were 7 children diagnosed up to 6 years old, 7 between 7 to 10 years old and 41 between 11 and ≤ 17 years old. There was no difference in the distribution of UC and CD between these age categories (P = 0.743). There was no difference in gender distribution in relation to adults. Children and adolescents with UC had a predominance of pancolitis, unlike adults (P = 0.001), and used aminosalicylates and immunomodulators for their treatment. Pediatric patients with CD did not present a difference in disease location but had a higher frequency of fistulizing behavior (P = 0.03) and perianal disease phenotype (P = 0.007) than adult patients. Patients with CD used more immunomodulators and biological therapy. Treatment with biological therapy was more frequently used in pediatric patients than in adults (P < 0.001). CONCLUSION: Although the data from this study demonstrate that incidence and prevalence rates are low in southeastern Brazil, these data demonstrate the severity of IBD in pediatric patients, with the need for early diagnosis and therapy, avoiding serious damage.

DISCONTINUATION RATES FOLLOWING A SWITCH FROM A REFERENCE TO A BIOSIMILAR BIOLOGIC IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

Taxas de descontinuação do tratamento após a troca de um biológico originador por um biossimilar em pacientes com doenças inflamatórias intestinais: revisão sistemática e metanálise / Discontinuation rates following a switch from a reference to a biosimilar biologic in patients with inflammatory bowel disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

RESUMO CONTEXTO: Os biológicos revolucionaram o tratamento da doença inflamatória intestinal (DII). Ademais, esses medicamentos influenciaram os custos relacionados ao tratamento. Tal aumento significativo nos gastos com o tratamento motivou desenvolvimento dos biossimilares. OBJETIVO: Esta revisão sistemática e metanálise objetivou avaliar a taxa de descontinuação de medicamentos na população com DII que foi submetida à troca do biológico originador para um biossimilar, em estudos observacionais que abordaram possíveis razões para a descontinuação do tratamento. MÉTODOS: Tendo como base de dados Medline (via PubMed), EMBASE, Cochrane Library e resumos de congressos médicos, foram rastreados artigos com relatos de troca de um biológico originador por um biossimilar, com acompanhamento pós-troca de no mínimo 6 meses ou três infusões. Todas as informações disponíveis sobre as taxas de descontinuação foram avaliadas. RESULTADOS: Foram incluídos no total 30 estudos observacionais, envolvendo 3.594 pacientes com DII. Vinte e seis estudos relataram uma mudança do infliximabe para CT-P13, dois estudos envolveram uma mudança para o SB2, e as informações sobre a troca não estavam disponíveis em dois estudos. As taxas de descontinuação foram de 8%, 14% e 21% aos 6, 12 e 24 meses, respectivamente. Os principais motivos para a descontinuação do medicamento e seus respectivos riscos foram: agravamento da doença (2%), remissão (4%), perda de adesão (4%), eventos adversos (5%) e perda de resposta (7%). A qualidade da evidência variou de baixa a muito baixa, dependendo do resultado analisado. Os sintomas subjetivos que levaram à descontinuação do medicamento foram relatados com pouca frequência, e o efeito nocebo foi claramente avaliado em apenas um dos artigos incluídos. CONCLUSÃO: As taxas de descontinuação após a mudança para um biossimilar em pacientes com DII aumentam com o tempo. No entanto, não foi possível confirmar o efeito nocebo como motivo da descontinuação. Portanto, ainda são necessários estudos em longo prazo avaliando o uso de biossimilares para monitorar eventos adversos e potenciais efeitos nocebo na vigilância pós-comercialização.