Consenso internacional sobre medición de calprotectina en EII

Ferdinando D’Amico, David T. Rubin, Paulo Gustavo Kotze, Fernando Magro, Britta Siegmund, Taku Kobayashi, Pablo A. Olivera, Peter Bossuyt, Lieven Pouillon, Edouard Louis, Eugeni Domènech, Subrata Ghosh, Silvio Danese, Laurent Peyrin‐Biroulet


Fecal calprotectin (FC) is a non‐invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard.


Our aim was to provide clear position statementsabout the pre‐analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus.

Materials & Methods

Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed.


Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results.


FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests.


FC concentrations guide clinicians’ treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement.


High ulcerative colitis and Crohn’s disease ratio in a population-based registry from Córdoba, Argentina

Domingo Balderramo, Juan Trakal, Pablo Herrera Najum, Melina Vivas, Roxana Gonzalez, Analía Benavidez, Daniela López Villa, Diego Daino, Karina Raiden, Andrés Germán, María Alicia Corzo, Javier Ponce de León, Luciana Ferrer, Carlos Germán, Silvina Bálzola, Adriana Idoeta, Fabián Zárate, María Rosa Defagó, Grupo Córdoba de Cooperación para el Manejo y Estudio de la Enfermedad Inflamatoria Intestinal (CEMEI Group)

Background: Few studies have described the epidemiology and clinical behavior of inflammatory bowel disease (IBD) in South America. The aim of this study was to report on the prevalence, phenotype, and treatment of patients with IBD diagnosis in Capital Department of the Province of Córdoba, Argentina.

Methods: Data from adult patients (≥ 18 years-old) with IBD diagnosis that attended 12 public or private centers between 05/2014 and 05/2019 were included in a common registry.

Results: A total of 655 patients were included (females: 53.4%). The ratio of ulcerative colitis (UC) (n = 561) to Crohn’s disease (CD) (n = 88) was 6.38, with age-adjusted IBD prevalence being 70.1 (95% confidence interval 70.08-70.12) cases/100,000 habitants. Extraintestinal manifestations were diagnosed in 22.8% of patients, and left-side colitis (46%) was the most frequent extension in UC patients. In CD patients, colonic involvement (55.7%) and non-stricturing/non-penetrating behavior (74%) were the most frequent presentations. Biologic therapy was used in 36.4% of CD patients and 9.1% of UC patients (P<0.001).

Conclusion: In this population registry study, IBD prevalence was similar to that reported in other series in the region. A higher UC/CD ratio was observed due to the lower prevalence of CD compared to similar studies in South America.

Keywords: Argentina; Inflammatory bowel disease; Prevalence; South America.

Conflict of interest statement

Conflict of Interest None declared.


Predicting Outcomes in Pediatric Ulcerative Colitis for Management Optimization:
Systematic Review and Consensus Statements from PIBD-Ahead Program

Esther Orlanski Meyer, Martine Aardoom, Amanda Ricciuto, Dan Navon, Nicholas Carman, Marina Aloi, Jiri Bronsky, Jan Däbritz, Marla Dubinsky, Séamus Hussey, Peter Lewindon, Javier Martin De Carpi, Víctor Manuel Navas-López, Marina Orsi, Frank M. Ruemmele, Richard K. Russell, Gabor Veres, Thomas D. Walters, David C. Wilson, Thomas Kaiser, Lissy de Ridder, Anne Griffiths, Dan Turner

Background and aims

A better understanding of prognostic factors in ulcerative colitis (UC) could improve patient management and reduce complications. We aimed to identify evidence-based predictors for outcomes in pediatric UC, which may be used to optimize treatment algorithms.


Potential outcomes worthy of prediction in UC were determined by surveying 202 experts in pediatric UC. A systematic review of the literature, with selected meta-analysis, was performed to identify studies that investigated predictors for these outcomes. Multiple national and international meetings were held to reach consensus on evidence-based statements.


Consensus was reached on 31 statements regarding predictors of colectomy, acute severe colitis (ASC), chronically active pediatric UC, and cancer or mortality. At diagnosis, disease extent (six studies, n=627; P=.035), Pediatric Ulcerative Colitis Activity Index (PUCAI) score (four studies, n=318; P<.001), hemoglobin, hematocrit, and albumin may predict colectomy. In addition, family history of UC (two studies, n=557; P=.0004), extraintestinal manifestations (four studies, n=526; P=.048), and disease extension over time may predict colectomy, while primary sclerosingcholangitis (PSC) may be protective. ASC may be predicted by disease severity at onset and hypoalbuminemia. Higher PUCAI score and C-reactive protein on day 3 and 5 of hospital admission predict failure of intravenous steroids. Risk factors for malignancy included concomitant diagnosis of PSC, longstanding colitis (>10 years), male sex, younger age at diagnosis, and thiopurine use.


These evidence-based consensus statements offer predictions to be considered for a personalized medicine approach in treating pediatric UC.


Antitumor Necrosis Factor Agents to Treat Endoscopic Postoperative Recurrence of Crohn’s Disease: A Nationwide Study With Propensity-Matched Score Analysis

Cañete, Fiorella1,2,3; Mañosa, Míriam1,2; Pérez-Martínez, Isabel4; Barreiro-de Acosta, Manuel5; González-Sueyro, Ramiro C.6; Nos, Pilar2,7; Iglesias-Flores, Eva8; Gutiérrez, Ana9; Bujanda, Luis2,10; Gordillo, Jordi11; Ríos León, Raquel12; Casanova, María José2,13; Villoria, Albert2,3,14; Rodríguez-Lago, Iago15,16; López Serrano, Pilar17; García-Herola, Antonio18; Ramírez-de la Piscina, Patricia19; Navarro-Llavat, Mercè20; Taxonera, Carlos21,22; Barrio, Jesús23; Ramos, Laura24; Navarro, Pablo25; Benítez-Leiva, Olga26; Calafat, Margalida1,3; Domènech, Eugeni MD, PhD1,2, on behalf of the INFLIRECU study

1Gastroentorology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain;
2CIBERehd, Madrid, Spain;
3Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain;
4Gastroentorology Department, Hospital Universitario Central de Asturias, Oviedo, Spain;
5Gastroentorology Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain;
6Gastroentorology Department, Hospital Universitari Clínic, Barcelona, Spain;
7Gastroentorology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain;
8UGC Digestivo, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain;
9Gastroentorology Department, Hospital General Universitario de Alicante, Alicante, Spain;
10Gastroentorology Department, Hospital Universitario de Donostia, Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain;
11Gastroentorology Department, Hospital de La Santa Creu i Sant Pau, Barcelona, Spain;
12Gastroentorology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain;
13Gastroentorology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain;
14Gastroentorology Department, Hospital Parc Taulí, Sabadell, Spain;
15Gastroentorology Department, Hospital de Galdakao, Galdakao, Spain;
16Gastroentorology Department, Biocruces Health Research Institute, Barakaldo, Vizcaya, Spain;
17Gastroentorology Department, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain;
18Gastroentorology Department, Hospital Marina Baixa de Villajoyosa, Alicante, Spain;
19Gastroentorology Department, Hospital Universitario Araba, Vitoria, Spain;
20Gastroentorology Department, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain;
21Gastroentorology Department, Hospital Clínico San Carlos, Madrid, Spain;
22Gastroentorology Department, Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain;
23Gastroentorology Department, Hospital Universitario Río Hortega, Valladolid, Spain;
24Gastroentorology Department, Hospital Universitario de Canarias, La Laguna, Spain;
25Gastroentorology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain;
26Gastroentorology Department, Hospital Universitari Mútua Terrassa, Terrassa, Spain.

Correspondence: Eugeni Domènech, MD, PhD. E-mail:


Patients with Crohn’s disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR.


Multicenter, retrospective, study of patients with Crohn’s disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively.


A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13–54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04–4.46; P = 0.03, and OR 2.34, 95% CI 1.18–4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65–6.05; P < 0.01, and OR 2.01, 95% CI 1.05–3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis.


In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.


Treatment Adherence in Inflammatory Bowel Disease Patients From Argentina: A Multicenter Study Lasa 1 2, Gustavo Correa 3, Claudia Fuxman 4, Laura Garbi 3, Maria Eugenia Linares 5, Pablo Lubrano 6, Astrid Rausch 1, Martin Toro 7, Martin Yantorno 3, Ignacio Zubiaurre 1, Laurent Peyrin-Biroulet 8, Pablo Olivera 2 6

1Gastroenterology Department, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina.
2Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina.
3Gastroenterology Department, Hospital Interzonal General de Agudos «General José de San Martín», La Plata, Argentina.
4Gastroenterology Department, Hospital Universitario Fundacion Favaloro, Buenos Aires, Argentina.
5Gastroenterology Department, Hospital de Clínicas «José de San Martín», Buenos Aires, Argentina.
6Gastroenterology Department, Sanatorio Mater Dei, Buenos Aires, Argentina.
7Gastroenterology Department, Hospital Universitario, Universidad Nacional de Cuyo, Mendoza, Argentina.
8INSERM U954 and Department of Hepatogastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre-lès-Nancy, France.

Methods: A multicenter cross-sectional study involving seven referral centers from three cities of Argentina was undertaken. Patients with a diagnosis of ulcerative colitis (UC), Crohn’s disease (CD), or indeterminate colitis (IBDU/IC) were invited to answer an anonymous survey, which included a 5-point Likert scale to evaluate adherence to therapies. Independent variables associated with inadequate adherence were evaluated.

Results: Overall, 447 UC/IBDU and 135 CD patients were enrolled. Median age was 37 years (range 21-72); 39.8% were male; median time from diagnosis was 6 years (0.5-35). 91.4% were under treatment with at least one oral medication; 50.3% of patients reported inadequate adherence to oral medications. Patients with UC/IBDU had a lower risk of inadequate adherence when compared to patients with CD (OR 0.57 (0.37-0.87)). 21.8% reported inadequate adherence to biologics; subcutaneous administration was significantly associated with inadequate adherence to biologics (OR 4.8 (1.57-14.66)).

Conclusion: Inadequate treatment adherence is common among patients with IBD, and potentially modifiable factors were identified.


Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-mediated Diseases: A Systematic Review and Meta-Analysis

Pablo A. Olivera,1,* Juan S. Lasa,1,2,* Stefanos Bonovas,3,4 Silvio Danese,3,4 and Laurent Peyrin-Biroulet5

1Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina;
2Gastroenterology Department, Hospital Británico de Buenos Aires, Argentina;
3Department of Biomedical Sciences, Humanitas University, Milan, Italy;
4IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy; and
5INSERM NGERE and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-lés-Nancy, France

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e18. Learning

Objective: Upon completion of this CME activity, successful learners will be able to identify the safety profile of Janus Kinases (JAK) inhibitors in patients with Inflammatory Bowel Disease and other Immune-mediated Diseases.

BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoria-sis, or ankylosing spondylitis. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference data-bases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous throm-boembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS: We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40–1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04–2.37). CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.

Keywords: NMSC; IBD; Immunosuppression; Small Molecule.