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Article in English | WPRIM | ID: wpr-922575


OBJECTIVE@#To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α).@*METHODS@#In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1β and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot.@*RESULTS@#In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1β, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05).@*CONCLUSION@#HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.

Animals , Colitis, Ulcerative/drug therapy , Dextran Sulfate , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , NF-kappa B , Scutellaria baicalensis , Tumor Necrosis Factor-alpha
J. coloproctol. (Rio J., Impr.) ; 41(1): 96-103, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1286968


Abstract The purpose of this review was to identify interventions that improve adherence to medications in patients with ulcerative colitis (UC). The literature search was carried out between April and June 2020 in the PubMed/MEDLINE database, with the combination of MeSH terms medication adherence; intervention; ulcerative colitis; and inflammatory bowel disease.We restricted our search to articles published in English and Portuguese between March 2010 and March 2020. After the selection, recovery of fulltext articles and analysis of the defined criteria, the interventions described in the studies were classified into four domains: educational; behavioral, cognitive behavioral, and multicomponent. In total, six clinical trials met the inclusion criteria and were analyzed. Half of the studies (3; 50%) used multicomponent interventions, 2 (33.3%) focused on behavioral interventions, and 1 (16.7%) applied isolated educational interventions. All studies used indirect methods to measure adherence, with an emphasis on scales and questionnaires. Half of the studies (3; 50%) showed a positive impact on adherence in patients with UC, with evidence that multicomponent interventions, when properly implemented in a clinical trial combining direct and indirect methods to measure medication adherence, appear to increase the chances of better results. We believe that future studies focusing on improving adherence in patients with UC are necessary.

Resumo O objetivo desta revisão foi identificar intervenções para a melhoria da adesão a medicamentos em pacientes com colite ulcerativa (CU). A busca na literatura foi realizada entre abril e junho de 2020 na base de dados do PubMed/MEDLINE, com a combinação dos descritores medication adherence; intervention; ulcerative colitis; e inflammatory bowel disease. Restringimos a busca aos artigos publicados em inglês e português entre março de 2010 e março de 2020. Após a seleção, recuperação dos textos dos artigos, e análise dos critérios definidos, as intervenções descritas nos estudos foram classificadas em quatro domínios: educacional; comportamental, cognitivo comportamental, e multicomponente. No total, seis ensaios clínicos atenderam aos critérios de inclusão e foram analisados. Metade dos estudos (3; 50%) usaram intervenções do tipo multicomponente, 2 (33.3%) centraram-se em intervenções comportamentais, e 1 (16.7%) aplicou intervenções educacionais isoladamente. Todos os estudos utilizaram métodos indiretos para mensurar a adesão, comênfase em escalas e questionários. Metade dos estudos (3; 50%) demonstraram impacto positivo na adesão em pacientes com CU, com indícios de que intervenções do tipo multicomponente, quando apropriadamente implementadas em ensaio clínicos que associam métodos diretos e indiretos para a mensuração da adesão a medicamentos, parecem aumentar as chances de melhores resultados. Consideramos que estudos futuros centrados na melhoria da adesão em pacientes com CU se fazem necessários.

Humans , Male , Female , Colitis, Ulcerative/drug therapy , Medication Adherence/statistics & numerical data , Self-Management/statistics & numerical data
Article in Chinese | WPRIM | ID: wpr-879165


To explore the drug use rules of traditional Chinese medicine(TCM) in the treatment of ulcerative colitis, and to provide some references for clinical treatment. The full-text search of "ulcerative colitis+TCM" was conducted based on CNKI. The literatures published from 2000 to 2020 were selected, and the clinical prescriptions for ulcerative colitis were selected according to the inclusion and exclusion criteria. The statistical processing and association rule analysis were carried out with use of Excel 2013, Clementine 12.0 and IBM SPSS Statistics 25.0 statistical software. A total of 177 prescriptions were obtained after retrieval of 3 432 relevant literatures, including 93 oral prescriptions and 84 enema prescriptions. Among them, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Coptidis Rhizoma, Aucklandiae Radix and Paeoniae Radix Alba were the most frequently used drugs in oral administration, with the functions of tonifying, heat clearing and Qi regulating. The drugs with high frequency in enema included Bletillae Rhizoma, Coptidis Rhizoma, Sanguisorbae Radix, Phellodendri Chinensis Cortex and Sophorae Flavescentis Radix, with the functions of heat clearing, blood stopping and tonifying. Both oral and enema means of drugs were mainly of warm, cold and slightly cold properties, and bitter and sweet flavors, involving spleen, stomach, lung and large intestine. In cluster analysis, oral and enema drugs were divi-ded into 5 groups. Accordingly, in the treatment of ulcerative colitis, tonifying medicine, heat clearing medicine and Qi regulating medicine are often used for oral administration and heat clearing medicine, hemostatic medicine and tonifying medicine are often used for enema administration. On this basis, they are combined with diuretic drugs and astringent drugs respectively.

Colitis, Ulcerative/drug therapy , Data Mining , Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional
Article in Chinese | WPRIM | ID: wpr-879021


To explore the effect of Huangqin Decoction on ulcerative colitis(UC) pyroptosis, and to explain the mechanism of pyroptosis based on NOD-like receptor thermoprotein domain 3(NLRP3)/cysteine proteinase 1(caspase-1) pathway. The animal model of UC induced with 3% dextran sodium sulfate(DSS) was established. The experimental animals were divided into control group, model group, low-dose(4.55 g·kg~(-1)), medium-dose(9.1 g·kg~(-1)) and high-dose(18.2 g·kg~(-1)) Huangqin Decoction groups and salazosulfapyridine group(0.45 g·kg~(-1)). While modeling, intragastric administration was given for 7 consecutive days. On the 8 th day, the mice were euthanized, the colon length was collected, and the histopathological changes were observed by HE staining. The content of interleukin-18(IL-18) was observed by ELISA. The content of lactatedehydrogenase(LDH)was determined by microplate method. TUNEL assay kit was used to detect the cell death. The immunohistochemical staining was used to detect the expressions of NLRP3 and apoptosis-associated speck-like protein containing a CARD(ASC). Western blot was used to detect the expressions of interleukin-1β(IL-1β), caspase-1 and gasdermin D(GSDMD).The experimental study showed that compared with normal group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were significantly increased(P<0.05). Compared with model control group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were decreased, and these results were more significant in high-dose groups(P<0.05). The results of HE staining showed that Huangqin Decoction could improve the pathological changes of colon. Huangqin Decoction could inhibit UC cell pyroptosis, and the mechanism may be closely related to NLRP3/caspase-1 signaling pathway.

Animals , Caspase 1/genetics , Colitis, Ulcerative/drug therapy , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pyroptosis , Scutellaria baicalensis
Article in Chinese | WPRIM | ID: wpr-878931


This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Animals , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Colon , Dextran Sulfate/therapeutic use , Drugs, Chinese Herbal , Mice , Molecular Docking Simulation , Plasma
Article in Chinese | WPRIM | ID: wpr-887962


The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.

Animals , Colitis , Colitis, Ulcerative/drug therapy , Colon , Dextran Sulfate/toxicity , Disease Models, Animal , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Mice , Mice, Inbred C57BL , Sulfates
Article in Chinese | WPRIM | ID: wpr-921798


Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1β and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.

Animals , Colitis, Ulcerative/drug therapy , Dextran Sulfate , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Mice , Monoterpenes , Paeonia/chemistry , Plant Roots/chemistry
Arq. gastroenterol ; 57(4): 491-497, Oct.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1142345


BACKGROUND: Biological therapy and new drugs have revolutionized the treatment of inflammatory bowel disease. Ideally, the choice of medication should be a shared decision with the patient, aiming at greater satisfaction, compliance, and consequently, favorable clinical outcome. OBJECTIVE: This study aims to evaluate patient's preferences in the choice of their therapy and the factors that influence this choice. METHODS: This cross-sectional study enrolled 101 outpatients with Crohn's disease or ulcerative colitis. The inclusion criteria were age ≥18 years and no previous exposure to biological therapy. Patients' preferences were assessed through questions that addressed the preferred mode of administration (oral, subcutaneous, or intravenous) and the factors that determined the choice of medication (efficacy, medical indication, fear of medication, convenience, mode of application, and personal doctors' indication). RESULTS: The mean age was 43.6±13.5 years, 75.3% were female, and 81.2% were cases of ulcerative colitis. Regarding the mode of administration, the majority of patients preferred oral (87.1%), followed by intravenous (6.93%) and subcutaneous (5.94%) medications. The reasons were "I prefer to take it at home" (42.57%), "I have more freedom" (36.63%), "I don't like self-application" (29.70%), and "I believe it works better" (19.80%). Younger patients and patients in clinical disease activity preferred intravenous mode compared to the oral route (P<0.05). Doctor's opinion (98%) was an important factor associated with the medication choice. CONCLUSION: Oral route was the preferred mode of administration and most patients took their physician's opinion into account in their choice of medication.

RESUMO CONTEXTO: A terapia biológica e os novos medicamentos revolucionaram o tratamento da doença inflamatória intestinal. A escolha do medicamento deve ser compartilhada com o paciente, visando maior satisfação, adesão e, consequentemente, desfecho clínico favorável. OBJETIVO: Este estudo teve como objetivo avaliar as preferências do paciente na escolha de sua terapia e os fatores que influenciaram essa escolha. MÉTODOS: Este estudo transversal incluiu 101 pacientes ambulatoriais com doença de Crohn ou retocolite ulcerativa. Os critérios de inclusão foram idade ≥18 anos e nenhuma exposição prévia à terapia biológica. A preferência dos pacientes foi avaliada por meio de perguntas que abordaram o modo de administração preferido (oral, subcutâneo ou intravenoso) e os fatores que determinaram a escolha do medicamento (eficácia, indicação médica, medo da injeção, conveniência, modo de aplicação e opinião pessoal do médico). RESULTADOS: A idade média foi de 43,6±13,5 anos, 75,3% eram mulheres e 81,2% eram portadores de retocolite ulcerativa. Em relação ao modo de administração, a maioria dos pacientes preferiu os medicamentos orais (87,1%), seguidos dos endovenosos (6,93%) e subcutâneos (5,94%). Os motivos foram "prefiro aplicar em casa" (42,57%), "tenho mais liberdade com essa medicação" (36,63%), "não gosto de autoaplicação" (29,70%) e "acredito que funcione melhor" (19,80%). Pacientes jovens e pacientes em atividade clínica preferiram a via intravenosa em comparação com a via oral (P<0,05). A opinião do médico (98%) foi um fator importante associado à escolha do medicamento. CONCLUSÃO: A via oral foi preferida e a maioria dos pacientes levou em consideração a opinião do seu médico na escolha do medicamento.

Humans , Male , Female , Adult , Middle Aged , Aged , Gastrointestinal Agents/administration & dosage , Inflammatory Bowel Diseases/drug therapy , Colitis, Ulcerative/drug therapy , Administration, Oral , Patient Satisfaction , Patient Preference , Injections, Subcutaneous/statistics & numerical data , Biological Therapy , Gastrointestinal Agents/therapeutic use , Brazil , Cross-Sectional Studies , Surveys and Questionnaires , Middle Aged
Arq. gastroenterol ; 57(4): 416-427, Oct.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1142332


ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory affections of recurrent nature whose incidence and prevalence rates have increased, including in Brazil. In long term, they are responsible for structural damage that impacts quality of life, morbidity and mortality of patients. OBJECTIVE: To describe the profile of physicians who treat IBD patients as well as the characteristics of IBD care, unmet demands and difficulties. METHODS: A questionnaire containing 17 items was prepared and sent to 286 physicians from 101 Brazilian cities across 21 states and the Federal District, selected from the register of the State Commission of the "Study Group of Inflammatory Bowel Disease of Brazil" (GEDIIB). RESULTS: The majority of the physicians who answered the questionnaire were gastroenterologists and colorectal surgeons. More than 60% had up to 20 years of experience in the specialty and 53.14% worked at three or more locations. Difficulties in accessing or releasing medicines were evident in this questionnaire, as was referrals to allied healthy professionals working in IBD-related fields. More than 75% of physicians reported difficulties in performing double-balloon enteroscopy and capsule endoscopy, and 67.8% reported difficulties in measuring calprotectin. With regard to the number of patients seen by each physician, it was shown that patients do not concentrate under the responsibility of few doctors. Infliximab and adalimumab were the most commonly used biological medicines and there was a higher prescription of 5-ASA derivatives for ulcerative colitis than for Crohn's disease. Steroids were prescribed to a smaller proportion of patients in both diseases. The topics "biological therapy failure" and "new drugs" were reported as those with higher priority for discussion in medical congresses. In relation to possible differences among the country's regions, physicians from the North region reported greater difficulty in accessing complementary exams while those from the Northeast region indicated greater difficulty in accessing or releasing medicines. CONCLUSION: The data obtained through this study demonstrate the profile of specialized medical care in IBD and are a useful tool for the implementation of government policies and for the Brazilian society as a whole.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII) são afecções inflamatórias crônicas de caráter recorrente, cujas taxas de incidência e prevalência têm aumentado, inclusive no Brasil. A longo prazo, são responsáveis por danos estruturais que impactam na qualidade de vida, morbidade e mortalidade dos pacientes. OBJETIVO: Avaliar o perfil dos médicos que atendem pacientes com DII, assim como as características deste atendimento, demandas não atendidas e dificuldades. MÉTODOS: Um questionário contendo 17 variáveis foi elaborado e enviado para médicos, selecionados a partir do cadastro da Comissão das Estaduais do Grupo de Estudos da Doença Inflamatória Intestinal do Brasil (GEDIIB), totalizando 286 médicos de 101 cidades brasileiras distribuídas por 21 estados e Distrito Federal. RESULTADOS: A maioria dos médicos que respondeu o questionário foram Gastroenterologistas e Coloproctologistas. Mais de 60% tinham até 20 anos de atuação na especialidade e 53,14% trabalhavam em três locais ou mais. A dificuldade no acesso ou liberação de medicamentos ficou evidenciada neste questionário, assim como a dificuldade no encaminhamento para profissionais não médicos que atuam em DII. Mais de 75% dos médicos relataram dificuldades para realização de enteroscopia por duplo balão e cápsula endoscópica, e 67,8% para realização da calprotectina. Em relação ao número de pacientes atendidos por cada médico, foi evidenciado que não há uma concentração de pacientes sob a responsabilidade de poucos médicos. O infliximabe e o adalimumabe foram os biológicos mais utilizados e ficou evidenciada prescrição maior de derivados de 5-ASA para retocolite ulcerativa quando comparada à doença de Crohn. Os corticoides foram prescritos para uma parcela menor de pacientes em ambas doenças. Os temas "falha a terapia biológica" e "novas drogas" foram referidos como aqueles com maior prioridade para discussão em eventos científicos. Em relação às possíveis diferenças entre cada região e o restante do país, os médicos da região Norte relataram maior dificuldade no acesso a exames complementares e os médicos da região Nordeste, maior dificuldade no acesso ou liberação de medicamentos. CONCLUSÃO: Os dados obtidos por meio deste estudo mostram o perfil do atendimento médico especializado em DII e podem se constituir em ferramenta útil para para elaboração de políticas governamentais e para sociedade brasileira como um todo.

Humans , Physicians , Inflammatory Bowel Diseases/therapy , Colitis, Ulcerative/drug therapy , Quality of Life , Brazil/epidemiology , Infliximab
Rev. méd. Chile ; 148(7): 1039-1043, jul. 2020. graf
Article in Spanish | LILACS | ID: biblio-1139408


Biological therapy dramatically changed the management of Ulcerative Colitis (UC). However, a significant number of these patients fail to respond or have secondary loss of response to this strategy. In this clinical situation, the options include intensification of anti-TNF therapy, the use of a second anti-TNF or being switched to another drug class. Among the later, tofacitinib, an oral small molecule directed against the JAK/STAT pathway, is safe and effective in inducing and maintaining remission in patients with moderate-severe UC. We report two patients with UC refractory to conventional treatment and biological therapy, who responded successfully to the use of tofacitinib.

Humans , Male , Middle Aged , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Colitis, Ulcerative/drug therapy , Protein Kinase Inhibitors/therapeutic use , Colitis, Ulcerative/diagnostic imaging , Colonoscopy , Treatment Outcome
Arq. gastroenterol ; 57(1): 69-73, Jan.-Feb. 2020. tab
Article in English | LILACS | ID: biblio-1098064


ABSTRACT BACKGROUND: Patients with inflammatory bowel disease (IBD) vaccinated for hepatitis B have a low success rate in achieving protective antibody levels. The main factors suggested for this are IBD itself and the use of immunosuppressive drugs. OBJECTIVE: To evaluate the concentration of anti-HBs antibodies and to verify factors associated with the effectiveness of hepatitis B vaccination in patients with IBD. METHODS: This is a prospective, consecutive, observational, descriptive and analytical, non-randomized, qualitative study that evaluated the levels of anti-HBs antibodies in IBD patients at the Interdisciplinary Inflammatory Bowel Disease Clinic of the Family and Community Health Unit of UNIVALI - Itajaí, Santa Catarina. RESULTS: Thirty-six patients were vaccinated against hepatitis B virus (HBV), of which 29 were female. The average age was 46.2 years. Regarding the type of IBD, twenty-four patients had Crohn's disease and the duration of inflammatory bowel disease was 74 months. Fifteen patients were on concomitant immunosuppressive therapy. The effective response rate to HBV vaccine was 72.2%, verified by anti-HBs titration ≥10 UI/L. Statistical analysis revealed a negative response to vaccination in patients with Crohn's disease and immunosuppressive drugs. CONCLUSION: The success rate of HBV immunization in IBD patients is low compared to the general population. Type of disease and use of immunosuppressive drugs appear to influence the vaccine response.

RESUMO CONTEXTO: Os pacientes com doenças inflamatórias intestinais (DII) vacinados para hepatite B possuem baixa taxa de sucesso em alcançar níveis protetores de anticorpos. Os principais fatores sugeridos para isso são a própria DII e o uso de medicamentos imunossupressores. OBJETIVO: Avaliar a titulação de anticorpos anti-HBs e verificar fatores associados a efetividade da vacinação contra hepatite B em pacientes com DII. MÉTODOS: Trata-se de um estudo prospectivo e consecutivo, de caráter observacional, descritivo e analítico, não-randomizado, qualiquantitativo, que avaliou a titulação de anticorpos anti-HBs em pacientes portadores de DII no Ambulatório Interdisciplinar de Doença Inflamatória Intestinal da Unidade de Saúde da Família e Comunitária da UNIVALI - Itajaí, Santa Catarina. RESULTADOS: Trinta e seis pacientes foram vacinados contra o vírus da hepatite B (VHB), destes, 29 eram do sexo feminino. A média de idade foi de 46,2 anos. Em relação ao tipo de DII, 24 pacientes eram portadores de doença de Crohn e o tempo médio de doença inflamatória intestinal encontrado foi de 74 meses. Quinze pacientes estavam em uso de terapia imunossupressora concomitante à vacinação. A taxa de resposta à vacina contra o VHB foi de 72,2%, verificada através de titulação de anti-HBs ≥10 UI/L. A análise estatística revelou uma resposta negativa à vacinação em pacientes em uso de medicamentos imunossupressores e portadores de doença de Crohn. CONCLUSÃO: A taxa de sucesso na imunização contra o VHB em pacientes com DII é baixo quando comparado à população em geral. Tipo de doença e uso de medicamentos imunossupressores parecem desempenhar influência na resposta vacinal.

Humans , Male , Female , Adult , Colitis, Ulcerative/immunology , Crohn Disease/immunology , Hepatitis B virus/immunology , Hepatitis B Vaccines/immunology , Hepatitis B/diagnosis , Hepatitis B/prevention & control , Hepatitis B Antibodies/blood , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Prospective Studies , Hepatitis B Vaccines/administration & dosage , Qualitative Research , Seroconversion , Hepatitis B/immunology , Hepatitis B Surface Antigens/immunology , Immunosuppressive Agents/therapeutic use , Middle Aged
Arq. gastroenterol ; 57(1): 87-90, Jan.-Feb. 2020.
Article in English | LILACS | ID: biblio-1098055


ABSTRACT Inflammatory bowel disease comprises two distinct conditions - Crohn's disease and ulcerative colitis - which can be treated with immunomodulators. A non-neglectable proportion of these patients will need biologic therapy, and many patients under biologic treatment will experience either primary or secondary failure. As a consequence, clinical trials evaluating new therapeutic alternatives are being developed. These trials share common features, such as being controlled with placebo. Placebo use in clinical trials is a matter of intense debate. Those who support placebo use highlight the methodologic advantages placebo-controlled trials have. Those against placebo use argue that it would be against ethical principles in clinical research to expose a patient to placebo when a valid therapeutic alternative exists. In this review, we summarize the existing arguments for and against the use of placebo in the context of inflammatory bowel disease research. We finally suggest that it is very likely that in the near future inflammatory bowel disease trials will no longer be controlled with a placebo arm, but instead they will be non-inferiority trials with an active comparator.

RESUMO A doença inflamatória intestinal compreende duas condições distintas: a doença de Crohn e a retocolite ulcerativa, que podem ser tratadas com imunomoduladores. Uma proporção não negligenciável desses pacientes necessitará de terapia biológica e, muitos destes em tratamento biológico, experimentarão falha primária ou secundária. Como consequência, ensaios clínicos avaliando novas alternativas terapêuticas estão sendo desenvolvidos. Estes ensaios partilham características comuns, tais como ser controlado com placebo. O uso de placebo em ensaios clínicos é uma questão de intenso debate. Aqueles que apoiam o uso do placebo destacam as vantagens metodológicas que os ensaios controlados com placebo têm. Aqueles contra o uso de placebo argumentam que seria contra os princípios éticos na investigação clínica expor um paciente ao placebo quando uma alternativa terapêutica válida existe. Nesta revisão, resumimos os argumentos existentes a favor e contra o uso de placebo no contexto da pesquisa de doença inflamatória intestinal. Finalmente, sugerimos que é muito provável que em um futuro próximo os ensaios de doença inflamatória intestinal não serão mais controlados com um braço placebo; em vez disso, serão feitos ensaios de não-inferioridade com um comparador ativo.

Humans , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Placebos , Clinical Trials as Topic
In. Machado Rodríguez, Fernando; Liñares, Norberto; Gorrasi, José; Terra Collares, Eduardo Daniel. Manejo del paciente en la emergencia: patología y cirugía de urgencia para emergencistas. Montevideo, Cuadrado, 2020. p.167-179, ilus.
Monography in Spanish | LILACS, BNUY, UY-BNMED | ID: biblio-1343000
Arq. gastroenterol ; 56(3): 312-317, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1038718


ABSTRACT BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn's disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.

RESUMO CONTEXTO: Há escassez de dados sobre a eficácia e segurança do vedolizumabe nas doenças inflamatórias intestinais na América Latina. OBJETIVO: Descrever a primeira experiência observacional de mundo real com vedolizumabe em pacientes latino-americanos com doenças inflamatórias intestinais. MÉTODOS: Estudo retrospectivo multicêntrico observacional de pacientes com doença de Crohn (DC) e retocolite ulcerativa inespecífica (RCUI) que utilizaram vedolizumabe em qualquer fase de seu tratamento. Foram avaliadas a remissão e resposta clínicas (de acordo com o índice de Harvey-Bradshaw para DC e escore de Mayo para RCUI), cicatrização da mucosa, necessidade de cirurgia e eventos adversos. RESULTADOS: Foram incluídos 90 pacientes (52 com DC e 38 com RCUI), a maioria com exposição prévia a agentes anti-TNF (88,46% na DC e 76,31% na RCUI). Na DC (em análise conforme observado), as taxas de remissão nas semanas 12, 26 e 52 foram 42,89% (21/49), 61,9% (26/42) e 46,15% (12/26), respectivamente. Na RCUI, as taxas de remissão nas semanas 12, 26 e 52 foram de 28,94% (11/38), 36,66% (11/30) e 41,17% (7/17). As taxas de cicatrização da mucosa foram 36,11% na DC e 43,4% na RCUI. Durante o período do estudo, 7/52 pacientes com DC foram submetidos a cirurgia abdominal maior e 4/38 pacientes com RCUI necessitaram de colectomia. CONCLUSÃO: O vedolizumabe foi eficaz na indução e manutenção da resposta e remissão clínicas em população refratária na DC e RCUI, com perfil de segurança favorável.

Humans , Male , Female , Adult , Gastrointestinal Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Crohn Disease/therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Remission Induction , Brazil , Retrospective Studies , Treatment Outcome , Middle Aged
Arq. gastroenterol ; 56(3): 318-322, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1038714


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.

Humans , Inflammatory Bowel Diseases/drug therapy , Tumor Necrosis Factor-alpha/therapeutic use , Biological Therapy , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Systematic Reviews as Topic , Latin America
Rev. Assoc. Med. Bras. (1992) ; 65(4): 547-553, Apr. 2019.
Article in English | LILACS | ID: biblio-1003058


The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Humans , Colitis, Ulcerative/drug therapy , Antibodies, Monoclonal/therapeutic use , Remission Induction , Brazil , Treatment Outcome , Cyclosporine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Adalimumab/therapeutic use , Infliximab/therapeutic use , Clinical Decision-Making
Rev. méd. Chile ; 146(11): 1241-1251, nov. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-985697


Background: Primary non-response and secondary loss of response (LOR) are significant problems of biological therapy for inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) in IBD patients receiving these drugs can improve outcomes. Aim: To measure serum infliximab levels and anti-infliximab antibodies (ATI) in patients with IBD post-induction phase and during maintenance therapy assessing the clinical course of IBD. Patients and Methods: Prospective study of IBD patients receiving infliximab between July 2016-May 2017. Group-A included patients who received induction therapy while Group-B included patients who were in maintenance therapy. TDM was performed in serum samples collected at weeks-14 and 30 in Group-A and before the infliximab maintenance dose in Group-B. Clinical scores, fecal calprotectin and endoscopic score were also evaluated. Results: Of 14 patients in Group-A, 57% achieved endoscopic response. Median serum infliximab concentrations at week-14 and 30 were 2.65 AU/mL (0.23-32.58) and 2.3 AU/mL (0.3-16.8), respectively. Patients with mucosal healing had non-significantly higher median infliximab concentrations at week- 14, as compared to week 30 (median 3.2 vs 2.2 AU/ml, respectively, p 0.6). ATI >10 ug/mL were found in one and seven patients at week-14 and 30, respectively. At 52 weeks of follow-up, four patients (31%) had LOR. Group-B included 36 patients, 33% had LOR. Median serum concentrations of infliximab were 1.4 AU/mL (0.27-7.03). No significant differences in serum infliximab concentration were observed between patients in remission and those with inflammatory activity. Seventeen patients had ATI >10 ug/mL. Conclusions: Clinical algorithms using TDM might help to optimize the pharmacological therapy of IBD.

Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Young Adult , Gastrointestinal Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Drug Monitoring/methods , Infliximab/therapeutic use , Reference Values , Severity of Illness Index , Gastrointestinal Agents/blood , Enzyme-Linked Immunosorbent Assay , Colitis, Ulcerative/diagnostic imaging , Crohn Disease/diagnostic imaging , Prospective Studies , Reproducibility of Results , Colonoscopy , Treatment Outcome , Statistics, Nonparametric , Infliximab/blood
Arq. gastroenterol ; 55(2): 198-200, Apr.-June 2018. graf
Article in English | LILACS | ID: biblio-1038706


ABSTRACT Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn's disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.

RESUMO Os inibidores das Janus kinases (JAK) têm sido incorporados ao tratamento de doenças imunomediadas, como artrite reumatoide e, além disso, têm sido testados no tratamento da psoríase e doenças inflamatórias intestinais, tanto na retocolite ulcerativa quanto na doença de Crohn. Tofacitinibe é uma droga do grupo das pequenas moléculas de uso oral que inibe as Janus kinases 1 e 3 e, em menor grau, a Janus kinases 2. Esta inibição promove o bloqueio de uma série de citocinas pró-inflamatórias que estão envolvidas na patogênese das doenças inflamatórias intestinais e desempenham importante papel nos processos imunes, tais como ativação, função e proliferação linfocitária. Nesta presente comunicação, relatamos um caso de um paciente portador de retocolite ulcerativa refratária a três agentes biológicos (infliximabe, adalimumabe e vedolizumabe), com diferentes mecanismos de ação, que recusou o tratamento cirúrgico, porém, apresentou boa resposta com o uso de tofacitinibe, com remissão clínica e endoscópica. Não foram evidenciados efeitos colaterais com a droga. O presente caso ilustra as dificuldades que podemos enfrentar em relação à identificação da expressão do correto mecanismo de ação envolvido na patogênese dos pacientes com retocolite ulcerativa e a importância de um novo agente terapêutico com diferente mecanismo de ação, como o tofacitinibe.

Humans , Male , Adult , Piperidines/therapeutic use , Colitis, Ulcerative/drug therapy , Integrins/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Integrins/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Infliximab/therapeutic use
Rev. Hosp. Clin. Univ. Chile ; 29(3): 189-197, 2018. Ilus., Graf., Tab.
Article in Spanish | LILACS | ID: biblio-999256


Ulcerative colitis (UC) is an autoimmune inflammatory chronic disease, which compromises the colonic mucosa continuously, affecting the rectum with a variable proximal extension to the cecum, in a relapsing and remitting way. The higher incidences and prevalence are described in Europe and North America, with no precise epidemiologic data from Chile. It usually presents in young patients with bloody diarrhea, with the diagnostic confirmation made by colonoscopic and histologic studies. There is no definitive cure for this condition, but the aim of the treatment is symptom resolution and endoscopic mucosal healing, based in the early use of 5-aminosalicylic acid drugs, steroids for a crisis, immunosuppressants, with some patients requiring biologic agents to reach remission. In some cases, colectomy is the last source for refractory disease or for treating colonic neoplasia. This review focuses on practical management of UC. (AU)

Adolescent , Adult , Middle Aged , Aged , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/therapy , Inflammatory Bowel Diseases , Colitis, Ulcerative/surgery , Colitis, Ulcerative/etiology
Gastroenterol. latinoam ; 29(supl.1): S68-S72, 2018. tab, ilus
Article in Spanish | LILACS | ID: biblio-1117874


Biological therapies have been essential for the management of inflammatory bowel disease; however, their high cost results in many patients being unable to access them. With time, commercial patents of many "original" biologics are reaching or almost in the point of reaching the expiration date of their licenses, which has allowed for the development of new agents known as biosimilars leading to a reduction of the cost of these therapies. The objective of this review is to explain what biosimilars are and show evidence of their effectiveness and safety.

Las terapias biológicas son parte fundamental en el manejo de la enfermedad inflamatoria intestinal, sin embargo los costos de éstas han hecho que muchos de los pacientes que tienen indicación de su uso, no puedan utilizarlas. Con el paso del tiempo, muchos biológicos "originales" están alcanzando o a punto de alcanzar el vencimiento de sus patentes, lo que ha llevado al desarrollo de nuevos agentes conocidos como biosimilares, determinando una disminución en los costos de estas terapias. Esta revisión tiene como objetivo explicar en qué consisten los biosimilares y la evidencia actual con respecto a su eficacia y seguridad.

Humans , Inflammatory Bowel Diseases/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Therapeutic Equivalency , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Chile , Interchange of Drugs