Clinical Efficacy of Modified Banxia Xiexintang Combined with Vedolizumab in Treatment of Crohn's Disease with Syndrome of Cold and Heat in Complexity / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy of modified Banxia Xiexintang combined with vedolizumab （VDZ） in the treatment of active moderate to severe Crohn's disease （CD） with the syndrome of cold and heat in complexity and the effect of the therapy on intestinal flora. MethodEighty patients were randomized based on the random number table method into a control group （40 cases） and an observation group （40 cases）. The control group was treated with VDZ， and the observation group was treated with modified Banxia Xiexintang （1 bag per day） combined with VDZ. The treatment in both groups lasted for 14 weeks and the follow-up lasted until the 52th weeks. The CD activity index （CDAI）， CD simplified endoscopic score （SES-CD）， inflammatory bowel disease questionnaire （IBDQ） score， and syndrome score of cold and heat in complexity were assessed before treatment， after treatment， and at the end of follow-up. The levels of hemoglobin （HGB）， hematocrit （HCT）， albumin （ALB）， C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-17 （IL-17）， and fecal calprotectin （FC） were measured before and after treatment. Intestinal flora was examined before and after treatment. The safety of the therapy was evaluated. ResultCompared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity decreased （P<0.05） and the IBDQ score increased after treatment （P<0.05）. Compared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity increased （P<0.05） and the IBDQ score decreased （P<0.05） at the end of follow-up. After treatment and at the end of follow-up， the observation group had lower scores of CDAI， SES-CD， and syndrome of cold and heat （P<0.05） and higher IBDQ score （P<0.05） than the control group. Moreover， the observation group had higher clinical remission rate（χ2=4.381，3.962） and response rate（χ2=5.541，4.306） and lower non-response rate（χ2=6.646，4.306） than the control group at the two time points （P<0.05）. The endoscopic remission rate（χ2=4.072，3.985） and response rate（χ2=4.528，5.161） in the observation group were higher than those in the control group （P<0.05）. After treatment， the HGB， HCT， and ALB levels in both groups elevated， and the observation group had higher levels than the control group （P<0.05）. The treatment in both groups lowered the levels of CRP， IL-6， TNF-α， IL-17， and FC （P<0.05）， and the observation group had lower levels of CRP， IL-6， TNF-α， IL-17， and FC than the control group after treatment （P<0.05）. The relative abundance of Bifidobacterium， Lactobacillus， and Prevotella increased （P<0.05）， while that of Proteus， Klebsiella， and Enterococcus decreased （P<0.05） in the two groups after treatment. Moreover， the changes in the relative abundance of these bacteria in the observation group were more obvious than those in the control group （P<0.05）. No adverse reactions related to the modified Modified Banxia Xiexintang were observed during the study period. ConclusionModified Banxia Xiexintang combined with VDZ can play a synergistic role and has good short-term and long-term efficacy. This therapy can improve the nutritional status， regulate intestinal flora， and reduce inflammatory injury in the treatment of moderate to severe active CD patients with the syndrome of cold and heat in complexity without causing severe adverse reactions.

Vedolizumabe comparado a agentes anti-TNF-α para indução e manutenção da remissão na doença de Crohn refratária a medicamentos biológicos: revisão rápida / Vedolizumab compared to anti-tnf-α agents for induction and maintenance of remission in biologic-refractory crohn's disease: a rapid review of systematic reviews

Vedolizumabe e anticorpos anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol). Indicação: Tratamento pessoas com doença de Crohn com falha a um agente biológico anti-TNF-α em tratamento prévio. Pergunta: Para adultos com doença de Crohn moderada a grave com falha terapêutica para anticorpos monoclonais anti-TNF-α, em tratamento de segunda linha, Vedolizumabe tem efeitos superiores aos anti-TNF-α para induzir e manter a remissão da doença? Objetivo: Investigar a eficácia e segurança do vedolizumabe, comparado aos agentes anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol), na indução e manutenção da remissão em pacientes refratários aos anti-TNF-α com doença de Crohn moderada a grave. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version) Resultados: Foi selecionada uma revisão sistemática, que atendida aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: Adalimumabe, disponível no Sistema Único de Saúde, é mais eficaz que vedolizumabe para induzir remissão clínica em pacientes tratados previamente com biológicos. Vedolizumabe não é mais eficaz que placebo para induzir remissão clínica. Vedolizumabe e adalimumabe são similares entre si e são mais eficazes que placebo para manter a remissão clínica. Não foram encontradas evidências comparando vedolizumabe a infliximabe ou certolizumabe pegol

Vedolizumab and anti-TNF-α antibodies (infliximab, adalimumab, certolizumab pegol). Indication: Treatment of people with Crohn disease who have failed an anti-TNF-α biological agent in previous treatment. Question: For adults with moderate to severe Crohn disease with treatment failure for anti-TNF-α monoclonal antibodies, in second-line treatment, does vedolizumab have superior effects to anti-TNF-α in inducing and maintaining disease remission? Objective: To investigate the efficacy and safety of vedolizumab, compared to anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), in the induction and maintenance of remission in moderate to severe Crohn disease refractory to anti-TNF-α previous treatment. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library databases and in registries of systematic reviews and clinical trials. The search has followed predefined strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: A systematic review was selected, which met the eligibility criteria, but no clinical trials were chosen as they did not meet the inclusion criteria. Conclusion: Adalimumab, available in the Brazilian Public Health System, is more effective than vedolizumab to induce clinical remission in patients previously treated with biologics. Vedolizumab is no more effective than placebo in inducing clinical remission. Vedolizumab and adalimumab are similar to each other and are more effective than placebo in maintaining clinical remission. No evidence was found comparing vedolizumab to infliximab or certolizumab pegol

Observation on the efficacy of vedolizumab in the treatment of patients with active Crohn′s disease / 中华消化杂志

Objective:To preliminary observe the clinical efficacy of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD).Methods:From March 2021 to October 2022, a total of 22 patients with active CD who received VDZ treatment at Zhongda Hospital, Southeast University were retrospectively enrolled. The general clinical data, laboratory indicators, imaging finding and endoscopic images of the patients were collected. The Crohn′s disease activity index (CDAI), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), clinical remission rate were evaluated at week 0, 2, 6 and 14 of VDZ administration. Meanwhile, the response rate under endoscopy and remission rate under endoscopy were evaluated after 14 weeks of VDZ administration. The related factors affecting the efficacy of VDZ were further analyzed. Kruskal-Wallis H test and Mann-Whithey U test were used for statistical analysis. The multiple logistic regression analysis was used to find the related factors affecting the clinical remission after VDZ treatment. Results:The CDAI at week 0, 2, 6 and 14 after treatment were 181.01 (160.11, 231.56), 148.05 (134.88, 200.52), 127.46 (91.44, 163.62), and 82.35 (63.50, 121.84), respectively, and the differences were statistically significant ( H=34.23, P<0.001); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=130.00, 80.00, 33.00; P=0.017, <0.001, and<0.001). The hs-CRP levels were 5.72 mg/L (3.59 mg/L, 11.10 mg/L), 2.86 mg/L (0.86 mg/L, 5.27 mg/L), 1.55 mg/L (0.86 mg/L, 9.89 mg/L) and 2.86 mg/L (0.86 mg/L, 3.12 mg/L), respectively, and the differences were statistically significant ( H=9.69, P=0.021); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=102.00, 109.00, 98.00; P=0.026, 0.045, and 0.011) .The level of ESR after 14 weeks of VDZ treatment was 8.00 mm/1 h (4.00 mm/1 h, 17.00 mm/1 h), which significantly decreased compared with that before treatment (17.00 mm/1 h(12.25 mm/1 h, 21.75 mm/1 h)), and the difference was statistically significant ( U=132.50, P=0.020). The clinical remission rates at week 2, 6 and 14 after VDZ treatment were 54.5% (12/22), 68.2% (15/22) and 86.4% (21/22), respectively, and the clinical response rates were 18.2% (4/22), 54.5% (12/22) and 95.5% (21/22), respectively. After 14 weeks of VDZ treatment, among 17 patients who underwent endoscopic re-examination, 9 patients achieved response under endoscopy and 3 patients achieved remission under endoscopy. Stenotic type and penetrating type of CD, previous use of glucocorticoids or immunosuppressants were risk factors of no clinical remission after VDZ treatment ( β=-4.586, -5.005 and -3.371; OR=0.010, 0.007 and 0.034; P=0.010, 0.025 and 0.045). While VDZ treatment for 14 weeks was a protective factor ( β=2.475, OR=11.885, P=0.011). Conclusions:VDZ can effectively relieve disease activity in patients with active CD. The disease behavior of CD, previous medication treatment of patients, and the duration of VDZ treatment may be related to the efficacy of VDZ.

The efficacy and safety of vedolizumab in the treatment of 81 cases of active ulcerative colitis: a single center retrospective study / 中华消化杂志

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active ulcerative colitis (UC).Methods:From November 1, 2020 to October 30, 2022, at the Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, 81 UC patients who received VDZ treatment and completed a 14-week follow-up were retrospectively selected. The clinical data of patients, including age, disease duration, disease activity of UC were collected. The VDZ efficacy evaluation included primary and secondary efficacy indicators. The primary efficacy indicator was the clinical remission rate after 14 weeks of VDZ treatment, and the secondary efficacy indicators included the clinical response rate, steroids-free remission rate, endoscopic remission rate after 14 weeks of treatment as well as the clinical response rate, clinical remission rate, steroids-free remission rate, secondary loss of response rate after 52 weeks of treatment. The adverse reactions during the treatment were recored. Taking clinical remission after 14 weeks of treatment as the dependent variable, univariate analysis was performed to identify the risk factors affecting clinical remission of VDZ. Binary logistic regression analysis was used for multivariate analysis to determine the independent risk factors of VDZ-included clinical remission. Chi-square test and Wilcoxon signed-rank test were used for statistical analysis.Results:Among the 81 UC patients, the age was 40.0 years old (29.0 years old, 53.5 years old) and the disease duration was 42.5 months (22.5 months, 94.7 months). The proportion of patients with mild active UC was 21.0% (17/81), the proportion of patients with moderate active UC was 64.2% (52/81), and the proportion of patients with severe active UC was 14.8% (12/81). After 14 weeks of treatment, the total Mayo score decreased from baseline level of 7.0 (6.0, 9.0) to 1.0 (0.0, 3.0), and the difference was statistically significant ( Z=-6.87, P<0.001). The clinical response rate was 84.0% (68/81) and the clinical remission rate was 69.1% (56/81) after 14 weeks of treatment. Of the 17 patients treated with combination of corticosteroid therapy, 10 achieved steroid-free remission, and the endoscopic remission rate was 34.8% (23/66). Of the 43 patients followed up to 52 weeks, the total Mayo score of UC patients decreased from baseline level of 7.0 (6.0, 9.0) to 0.0 (0.0, 1.0) after 52 weeks of treatment, and the difference was statistically significant ( Z=-3.25, P<0.001). The clinical response rate was 69.8% (30/43), and the clinical remission rate was 65.1% (28/43). Of the 13 patients treated with combination of corticosteroid therapy, 10 patients achieved steroid-free remission. The secondary loss of response rate was 15.2%(5/33) .The result of the univariate analysis showed that previous use of glucocorticoids was a risk factor of clinical remission after 14 weeks of VDZ treatment ( χ2=5.88, P=0.015). The result of multivariate logistic regression analysis showed that previous use of glucocorticoids was an independent risk factor of clinical remission after 14 weeks of VDZ treatment ( OR=3.429, 95% confidence interval 1.235 to 9.517, P=0.014). During the follow-up period, 12.3% (10/81) of patients developed Clostridium difficile infections, except for 1 case stopped VDZ treatment because the clinical response was not reached, remaining 9 cases continued VDZ treatment after received anti- Clostridium difficile treatment. Conclusion:VDZ has good clinical efficacy and safety in the treatment of Chinese UC patients, and patients with no history of glucocorticoid use may be more likely to achieve clinical remission after 14 weeks of treatment.

Efficacy and Safety of Vedolizumab in Patients With Moderate-to-severe Ulcerative Colitis: A Systematic Review and Meta-analysis / 胃肠病学

Background; Biological agents have become an important treatment for moderate-to-severe ulcerative colitis (UC). Studies have shown that vedolizumab (VDZ) has good efficacy. Ainis; To systematically evaluate the efficacy and safety of VDZ in the treatment of moderate-to-severe UC. Methods; Studies on VDZ, anti-tumor necrosis factor (TNF)-α in treatment of moderate-to-severe UC were retrieved from PubMed, Web of Science, EBSCO, The Cochrane Library, CNKI, SinoMed from the date of database establishment to August 2021. According to inclusion and exclusion criteria, literatures were screened and extracted. RevMan 5. 4 software was used to conducted meta-analysis. Results; Eleven studies involving 3 921 patients were included. Meta-analysis showed that the clinical response rate ( OR = 2. 14, 95% CI; 1. 73-2. 64, P<0.00001), the clinical remission rate (OR = 1.67, 95% CI; 1.42-1.96, P<0.00001), the endoscopic response rate (OR = 1.62, 95% CI; 1.29-2.03, P<0.000 1), and the histological response rate (OR = 1. 98, 95% CI; 1.61-2.44, P<0.000 01) in VDZ group were significantly higher than those in anti-TNF-α group. However, no significant difference in incidence of adverse reactions was found between the two groups (OR = 0.51, 95% CI; 0.26-1. 01, P = 0.05). Conclusions; Compared with anti-TNF-α, VDZ is more effective in the treatment of moderate-to-severe UC, and there is no significant difference in incidence of adverse reactions.

Progress of Research on Therapeutic Drug Monitoring in Treatment of Novel Biological Agents for Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease, and its treatment includes traditional medicines and biological agents. Therapeutic drug monitoring is an important tool to optimize the treatment of biological agents. Therapeutic drug monitoring of tumor necrosis factor inhibitors has been used to guide the clinical decision ⁃ making. However, the value of therapeutic drug monitoring of novel biological agents (vedolizumab and ustekinumab) in IBD remains unclear. This article summarized the pharmacokinetics, drug concentration and treatment outcome, optimization of the novel biological agents in the treatment of IBD.

Vedolizumab en tratamiento de colitis ulcerativa refractaria asociada con psoriasis: reporte de caso / Case Report of Vedolizumab Treatment of Refractory Ulcerative Colitis Associated with Psoriasis

Resumen Paciente con historia de psoriasis de difícil control y colitis ulcerativa de larga evolución, corticodependiente, requirió múltiples esquemas de tratamientos incluidos varios antagonistas de factor de necrosis tumoral (anti-TNF), con lo cual tuvo respuesta clínica aceptable y posterior pérdida de efectividad. En una exacerbación aguda de la colitis se utilizó vedolizumab, con lo cual se logró una notable mejoría clínica, y en el mantenimiento se llegó a cicatrización profunda (normalización endoscópica e histológica), además de mejoría significativa de las lesiones de psoriasis en el seguimiento a 12 meses. En lo conocido hasta ahora, es el primer caso con el uso de vedolizumab en esta indicación publicado en Colombia.

Abstract The patient had a long history of difficult to control psoriasis and ulcerative colitis and was dependent on corticosteroids. Multiple treatment schemes including several attempts with tumor necrosis factor (anti-TNF) antagonists had had acceptable clinical responses but subsequently lost effectiveness. During acute exacerbation of colitis, vedolizumab was used and achieved remarkable clinical improvement. During maintenance, deep healing was achieved (endoscopic and histological normalization). In addition, there was significant improvement of psoriasis lesions during follow-up. This is the first case to be published of the use of Vedolizumab to treat this condition in Colombia.

Evaluation of Efficacy and Safety of Vedolizumab in Treatment of Active Inflammatory Bowel Disease / 胃肠病学

Background: Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the gastrointestinal tract with a course of repeated episodes and remissions. Vedolizumab (VDZ), a selective blocker of interaction between leukocytes and vascular endothelium of the gut, has been demonstrated effective in treatment of active IBD. Aims: To systematically evaluate the efficacy and safety of VDZ for active IBD. Methods: PubMed, Embase, Cochrane Library and Google Scholar were retrieved to collect randomized controlled trials (RCTs) comparing VDZ and placebo in patients with IBD published in English before Aug. 2018. Meta-analysis was conducted by using RevMan 5.30 software. Results: Eight RCTs involving 3 159 active IBD patients were included. Meta-analysis showed that VDZ was superior to placebo in inducing clinical response, clinical remission and endoscopic remission in active UC (RR=1.62, 95% CI: 1.33-1.97, P<0.000 01; RR=2.45, 95% CI: 1.56-3.83, P<0.000 1; RR=1.75, 95% CI: 1.29-2.37, P=0.000 3, respectively) and in maintenance of clinical remission in inactive UC (RR=2.43, 95% CI: 1.73-3.41, P<0.000 01). Also, VDZ was superior to placebo in inducing clinical response and clinical remission in active CD (RR=1.47, 95% CI: 1.21-1.79, P=0.000 1; RR=1.87, 95% CI: 1.37-2.56, P<0.000 1, respectively). Subgroup analysis revealed that clinical remission was only achieved in CD patients naive to anti-tumor necrosis factor-α (TNF-α) therapy. Only one trial described the clinical remission in inactive CD, the results showed that VDZ was superior to placebo. Except for nasopharyngitis, adverse events were similar between VDZ group and placebo group. Conclusions: VDZ is safe and effective for induction and maintenance of remission in active IBD, but may be not more effective than placebo in CD patients failure to anti-TNF-α therapy.

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

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

Clinical aspects of Crohn's disease / 中国实用内科杂志

Crohn's disease (CD) is a chronic,relapsing and disabling inflammatory bowel disease.Although the cause is unknown,defects in innate and adaptive immune pathways have been identified and biological therapies that target key molecules have been designed and dramatically improved treatment of CD patients.The disease is currently increasing in China.The symptoms of CD are heterogeneous but commonly include abdominal pain,diarrhea and weight loss,which are largely dependent on the stages (early,active,remitted,and chronic active stages,respectively) of the disease.A single gold standard for the diagnosis of CD is not available.The diagnosis is confirmed by clinical evaluation and a combination of endoscopic,histological,radiological,and/or biochemical investigations.Behavior of the disease varies substantially during its course.About 13%～20% of patients with CD have a chronic active course of disease.67%～73% have a chronic intermittent course for several years.After 20 years most patients will need surgery.The life expectancy is slightly reduced.