Infliximab serum concentrations and disease activity in perianal fistulizing Crohn's disease: a cross-sectional study.

INTRODUCTION: Several studies associate the presence of higher serum concentrations of infliximab (IFX) with fistula healing in perianal Crohn's disease (CD). This study aimed to evaluate serum IFX concentrations in patients with perianal fistulizing CD (PFCD) in the presence or absence of general, clinical, and radiological activities. METHODS: This was a cross-sectional study in patients with PFCD during maintenance treatment with IFX from two centers. Serum IFX concentrations were measured before their next infusion and anal fistulas were evaluated by clinical examination and magnetic resonance imaging (MRI), whenever possible, performed 90 days before or after serum collection. According to clinical scores, radiological activity, and disease markers, patients were classified as in remission or active disease. Mean serum IFX concentrations were compared between the groups. RESULTS: Thirty-eight patients with PFCD were included. Demographic characteristics were similar in patients with remission or active disease. The overall mean serum IFX concentration of the entire sample (n = 38) was 5.21 ± 4.75 µg/mL (median 3.63; IQR 1.44-8.82). Serum IFX levels were 6.25 ± 5.34 µg/mL (median 3.62; IQR 1.95-11.03) in the 23 (60.5%) patients in remission and 3.63 ± 3.24 µg/mL (median 3.63; IQR 1.32-6.43; p = 0.226) in the 15 (39 .5%) who presented active disease. When evaluating general, clinical, and radiological activity of PFCD, and deep remission in isolation, no statistical difference between the groups was observed (p = 0.226, p = 0.418, p = 0.126, and p = 0.232, respectively). The 13 (34.2%) patients with an optimized dose of IFX had significantly higher serum concentrations than the remaining 25 (65.8%) with a standard dose: 8.33 ± 4.41 µg/mL (median 8.36; IQR 3.82-11.20) vs. 3.59 ± 4.13 µg/mL (median 1.97; IQR 1.18-3.85) -p = 0.002. Patients in remission and with an optimized IFX dose had significantly higher serum IFX concentrations than those with a standard dose (p = 0.006), whereas no significant difference was observed among those with active disease (p = 0.083). CONCLUSION: There were no differences in IFX serum concentrations in patients with clinical or radiological active PFCD as compared with those in remission. Patients with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose. Patients in remission and with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose.

Update of the PANCCO clinical practice guidelines for the treatment of ulcerative colitis in the adult population.

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice.

Darvadstrocel for the treatment of patients with perianal fistulas in Crohn's disease.

Despite significant advances in medical and surgical therapy for perianal fistulas in Crohn's disease (CD), treatment results are still modest, and a specific need for more effective therapies is a reality. Darvadstrocel is composed of expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue and constitutes the first stem cell therapy for perianal fistulizing CD to receive approval from the European Medicines Agency (EMA). This therapy is injected in both internal and external openings, as well as inside the fistula tracks, to induce fistula healing. In this monograph, the authors review the preclinical pharmacology of darvadstrocel, as well as pharmacokinetics and metabolism, and cover the main indications and detailed information on the efficacy and safety profile of the agent. Possible interactions with other agents used to treat CD are also explored. Darvadstrocel is a safe and effective therapy for perianal complex fistulas in CD, and represents the beginning of a new era of mesenchymal stem cell therapy in this difficult phenotype of the disease.

Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). / Situaciones especiales en la enfermedad inflamatoria intestinal: primer consenso latinoamericano de la Pan American Crohn's and Colitis Organisation (PANCCO) (Segunda parte).

This is the first Latin American Consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) regarding special situations in patients with inflammatory bowel disease (IBD). The aim of this consensus is to raise awareness in the medical community in all Latin American countries with respect to pregnancy, vaccinations, infections, neoplasms, including colorectal cancer, and pediatric issues in patients with IBD.

Diagnosis and treatment of inflammatory bowel disease: First Latin American Consensus of the Pan American Crohn's and Colitis Organisation. / Diagnóstico y tratamiento de la enfermedad inflamatoria intestinal: Primer Consenso Latinoamericano de la Pan American Crohn's and Colitis Organisation.

The incidence and prevalence of inflammatory bowel disease (IBD) has increased in recent years in several Latin American countries. There is a need to raise awareness in gastroenterologists and the population in general, so that early diagnosis and treatment of ulcerative colitis (UC) and Crohn's Disease (CD) can be carried out. It is important for all physicians to have homogeneous criteria regarding the diagnosis and treatment of IBD in Latin America. The Pan American Crohn's and Colitis Organisation (PANCCO) is an organization that aims to include all the countries of the Americas, but it specifically concentrates on Latin America. The present Consensus was divided into two parts for publication: 1) Diagnosis and treatment and 2) Special situations. This is the first Latin American Consensus whose purpose is to promote a perspective adapted to our Latin American countries for the diagnosis, treatment, and monitoring of patients with UC and CD.

Factors affecting the incidence of early endoscopic recurrence after ileocolonic resection for Crohn's disease: a multicentre observational study.

AIM: Early endoscopic recurrence is frequently observed in patients following resection for Crohn's disease (CD). However, factors affecting the incidence of an early postoperative endoscopic recurrence (EPER) have not been fully determined. The aim of this study was to evaluate risk factors for EPER after ileocolonic resection for CD. METHOD: This was a retrospective, international multicentre study, in which 127 patients with a first ileocolonoscopy conducted between 6 and 12 months after ileocolonic resection for CD were included. Endoscopic recurrence was defined as a Rutgeerts score of ≥ i2. The following variables were investigated as potential risk factors for EPER: gender, age at surgery, location and behaviour of CD, smoking, concomitant perianal lesions, preoperative use of steroids, immunomodulators and biologics, previous resection, blood transfusion, surgical procedure (open vs laparoscopic approach), length of resected bowel, type of anastomosis (side-to-side vs end-to-end), postoperative complications, granuloma and postoperative biological therapy. Variables related to the patient, disease and surgical procedure were investigated as potential risk factors for EPER, with univariate and multivariate (logistic regression) analyses. RESULTS: 43/127 (34%) patients had EPER at the time of the first postoperative ileocolonoscopy. In univariate analysis, only preoperative steroid use was significantly associated with a higher rate of EPER [21/45 patients (47%) on steroids and 22/82 patients (27%) without steroids (P = 0.04)]. In multivariate analysis, only preoperative steroid use was a significant independent risk factor for EPER (odds ratio 3.28, 95% confidence interval: 1.30-8.28; P = 0.01). CONCLUSIONS: This study found that only preoperative steroid use was a significant risk factor for EPER after ileocolonic resection for CD. Prospective studies are necessary to evaluate precisely the impact of perioperative medications on EPER rates.