Fernando Magro

University of Porto | UP · Departamento de Farmacologia e Terapêutica

Crohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria.Human peripheral blood monocyte-derived macrophages were obtained from CD pa...

Patients with inflammatory bowel disease (IBD) may have an increased risk of venous thrombosis (VTE). PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD. Overall, IBD patients have a two- to fourfol...

Objectives: Crohn's disease (CD) induces cumulative structural damage, initially characterized by a non-stenosing non-penetrating behavior (B1) with progression over time to a fibro-stenosing (B2) and/or penetrating phenotype (B3). Our aim was to assess the long-term evolution of disease behavior of CD and determine what factors predict phenotype...

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on intestinal fibrosis in inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms and markers of intestinal fibrosis as well as to suggest new therapeutic targets to prevent or treat fibrosis. The results of this workshop...

To the editors: The response to infliximab (IFX) in Crohn's disease (CD) and Ulcerative Colitis (UC) is initially good, although over time, a loss of response frequently occurs. Fifty percent of CD patients require IFX escalation,1 with regained responsiveness in majority of patients, at least in the short-term.2 Reports are scarcer regarding UC,...

Background: Patients with immune-mediated inflammatory diseases (IMIDs) treated with immunomodulatory therapy present an increased susceptibility to infections. Vaccination is a crucial element in the management of IMID patients; however, rates remain suboptimal. This study intended to clarify the adherence to prescribed vaccines. Materials and met...

Background Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages. Objective To review the recent learnings on the ability of blood...

Background and aims: The availability of biological agents for inflammatory bowel disease has increased over the past years. In this systematic review and meta-analysis, we aimed to explore time trends in clinical response and clinical remission rates in Crohn's disease (CD) patients treated with biologics while discussing the need for new strateg...

Inappropriate activation of Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NOD) is involved in many chronic disorders, including inflammatory bowel disease (IBD). Altered function and/or expression of Na+,K+-ATPase (NKA) and epithelial ion channels are the main cause of electrolyte absorption imbalance in IBD pa...

The i Support Therapy–Access to Rapid Treatment (iSTART) was an initiative to improve patient-centered management in mild-to-moderate ulcerative colitis (UC). Our aim was to update the iSTART recommendations in order to include fecal calprotectin (FC) in the monitoring of patients with UC and improve their management. Twelve physicians from nine co...

Background Improvement in clinical outcomes and normalisation of objective markers of inflammation, high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP), are considered treatment targets per STRIDE-II guidelines.1 We evaluated the effect of the oral selective Janus kinase inhibitor upadacitinib (UPA) on changes in hs-CRP, FCP,...

Background Early flare prediction is essential for the timely management of Crohn’s disease (CD) patients, allowing to optimize the available therapeutic toolbox and to decrease the disease burden. We aimed to evaluate the performance of readily available biomarkers (when evaluated at least once or more frequently during follow-up) and to develop r...

Background In ulcerative colitis (UC), persistent histological activity is associated with higher rates of relapse and long-term complications, even when endoscopic remission is achieved; therefore, histological healing is a potentially important treatment target. Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate...

Background Real-world treatment of ulcerative colitis (UC) requires a patient-centric, holistic definition of ‘comprehensive remission' that goes beyond standard regulatory definitions. In an international initiative, we reviewed aspects of UC that affect patients and attempted to achieve consensus on which aspects should be considered in a definit...

Background Histological remission is an important target for Ulcerative Colitis (UC) treatment; however, scoring of histological images is time-consuming and prone to inter and intra-observer variability. Thus, a need exists for an accurate, reproducible, and reliable automated method. Previously, we demonstrated an Artificial Intelligence (AI) Too...

Background and Objectives: At present, there is no consensus definition of mild-to-moderate disease activity in patients with ulcerative colitis. The objective of the present study was to establish a reliable definition of mild-to-moderate disease activity in adult patients with ulcerative colitis. Materials and Methods: Twelve physicians from arou...

Background Crohn’s disease (CD) and ulcerative colitis (UC) arise from a dysregulation of the balance between commensal microbiota and mucosal-associated immune system, in patients with genetic and environmental predisposition. Different pathophysiological mechanisms have been reported to influence disease history, with impact on disease phenotype...

Introduction: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. Methods: Multicenter retrospective study including 404...

Background: The effectiveness of Crohn's disease treatments for inducing histological outcomes has not been addressed systematically. We performed a systematic review and meta-analysis of randomized controlled trials in Crohn's disease to assess the impact of therapies on mucosal histopathology. Methods: Databases (MEDLINE, CENTRAL, Web of Scien...

Background and aims: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients trea...

Background & aim Advanced therapies for inflammatory bowel disease (IBD) could potentially lead to a state of immunosuppression with an increased risk of opportunistic infections (OIs). We aimed to update on the incidence of OIs among adult IBD patients in randomized controlled trials (RCTs) of approved biologics and small-molecule drugs (SMDs). Al...

Background: Clinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC. Objective: We aimed to evaluate the impact of disease clearance on long-term outcomes in UC patients. Methods: A multice...

Disproportionate activation of pattern recognition receptors plays a role in inflammatory bowel disease (IBD) pathophysiology. Diarrhea is a hallmark symptom of IBD, resulting at least in part from an electrolyte imbalance that may be caused by changes in potassium channel activity. We evaluated the impact of Toll-like receptors (TLRs) and nucleoti...

We performed a systematic review to investigate the definition of mild to moderate active ulcerative colitis (UC), and to describe predictors of good response to treatment in clinical trials assessing 5‐ASA and/or budesonide. Thirty‐nine randomized controlled trials were included. The UC Disease Activity Index (UCDAI) was the most frequent score us...

Background Endpoints to determine the efficacy and safety of medical therapies for Crohn’s disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing endpoints in a core outcome set (COS) for randomized controlled trials (RCTs) is a priority for drug development in inflammatory bowel dise...

b> Background: Inflammatory bowel diseases’ (IBD) increasing incidence and prevalence place a heavy health and economic burden on society. Objectives: This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care. Methods: The burden of disease was expressed using disa...

Background This systematic review and meta-analysis aims to assess composite and aggregate outcomes of observational studies in Crohn’s disease and to evaluate whether the number and type of variables included affect the frequency of the outcome. Methods MEDLINE [via PubMed], Scopus and Web of Science were searched to identify observational studie...

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. Methods Patients received tofacitinib 10 mg twice daily (BID) in an 8-week,...

Background: Inflammatory Bowel Disease (IBD) affects people from all age categories worldwide. While the incidence of the disease is stabilizing or decreasing in most western world countries, its prevalence is still increasing due to the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD...

Background The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn’s disease (CD) for health care systems from different perspec...

Background A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom m...

Objectives 5-aminosalicylate (mesalazine; 5-ASA) is an established first-line treatment for mild-to-moderate ulcerative colitis (UC). This study aimed to model the benefits of optimising 5-ASA therapy. Methods A decision tree model followed 10 000 newly diagnosed patients with mild-to-moderately active UC through induction and 1 year of maintenanc...

Background and aims Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the PROCTRIAL (Definition and endpoints for ulcerative PROCtitis in clinical TRIALs) initiative was to develop consensus statements for definitions, inclusion criteria, a...

Background STARDUST is a phase 3b randomized trial comparing two therapeutic strategies with ustekinumab (UST) in patients (pts) with Crohn’s disease (CD): treat-to-target (T2T) using early endoscopic assessment vs standard of care (SoC). Results from the Week (W)48 and long-term extension (LTE) (W48 to W104) were published previously.1,2 Here we e...

Background Observational studies are essential to analyse outcome reporting in inflammatory bowel disease. However, such studies are usually heterogeneous. Therefore, the development of core outcome sets to be included in future observational studies is of major importance. Composite and aggregate outcomes (in which an event is classified by the pr...

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations i...

In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highl...

The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care in rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients and healthcare professionals (HCPs). Subcutaneous (SC) formulations of biologics enable patient...

Objectives To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). Methods This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all...

Background Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes. Objective This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how...

Background and aims Subclinical intestinal inflammation is common in Crohn’s disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers. Methods The registry-based, prospective, observati...

Background and aims Filgotinib is a small molecule that selectively inhibits Janus kinase (JAK) type 1. It is already approved for the treatment of rheumatoid arthritis and is being evaluated for the management of patients with moderate to severe ulcerative colitis (UC). The purpose of this review is to provide an overview of the currently availabl...

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous...

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and methods: In this retrospective multicenter cohort study...

Background and aims: The role of thiopurines in therapeutic algorithms of Crohn's disease (CD) and Ulcerative colitis (UC) is being questioned. This work aimed to investigate current practice and future perspectives of Inflammatory Bowel Disease (IBD) physicians regarding the efficacy, safety, and role of precision medicine with thiopurines in IBD...

Background The STARDUST study demonstrated that ustekinumab (UST), using either a treat-to-target (T2T) or standard of care (SoC) strategy, may induce and maintain endoscopic and clinical response and remission in Crohn’s disease (CD). Primary endpoint, safety, and efficacy have been reported previously.1 Because corticosteroid (CS) sparing is an i...

Background The 48-week (W) interventional STARDUST trial assessed whether a treat-to-target (T2T) strategy using ustekinumab (UST) may optimize Crohn’s disease (CD) outcomes; primary efficacy and safety data have been reported before.1 Here we assessed which patient (pt) subgroups may benefit from T2T vs standard of care (SoC) in achieving endoscop...

Background A treat-to-target (T2T) strategy may optimize inflammatory bowel disease management. The STARDUST trial compared a T2T maintenance strategy against standard of care (SoC) in Crohn’s disease (CD) patients treated with ustekinumab (UST). The primary endpoint, safety, and efficacy data of STARDUST have been published previously.1 Here we pr...

Background With the development of new drugs for inflammatory bowel disease (IBD), the role of thiopurines in the therapeutic algorithm of Crohn’s disease (CD) and Ulcerative Colitis (UC) is questioned. We aimed to investigate the current practice and future perspective of IBD physicians regarding the efficacy, safety, and role of precision medicin...

Background: 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...

Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT1 /AT2 receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat m...

Several efforts have been made to improve the available therapeutic armamentarium of patients with immune-mediated inflammatory disorders (IMIDs) leading to the development of biobetters. To date, there is no commonly accepted definition of biobetters. Sixteen physicians with expertise in the field of IMIDs from eleven countries attended a virtual...

Introduction: In Crohn's disease (CD), the assessment of transmural inflammation and fibrosis is of utmost importance. This study aimed to quantify these parameters in CD ileal specimens and correlate them with disease progression. Methods: This is a retrospective unicentric study based on the analysis of archived specimens (n = 103) of primary...

Background Real-life-data regarding pharmacokinetics of vedolizumab in patients needing dose-optimization are scarce. We set to examine whether pre-optimization vedolizumab-levels associate with therapy-outcomes and which mechanisms explain the associations. Methods A multi-center observational study assessed the outcome of dose-increase in associ...

Introduction: Dipeptidyl peptidase-4 (DPP-4) is a membrane-bound glycoprotein that acts as a receptor but also exists in a soluble form. It has been recognized as a mediator of inflammation and considered a biomarker in inflammatory bowel disease (IBD). Methods: We evaluated a prospectively recruited cohort, consisting of 101 patients with IBD,...

Abstract Background The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a widely used instrument to assess Health-related Quality of Life (HRQoL) among inflammatory bowel disease (IBD) patients. Our aim was to translate and adapt the SIBDQ so that it could be adequately used in Portugal. Methods This is a prospective design cohort study u...

Introduction: Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (C...

Reproducibility in animal research is crucial for its reliance and translational relevance. The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced model of inflammatory bowel disease (IBD) is widely used but inconsistently and incompletely characterized throughout the literature. This hinders comparisons between studies and influences the low rate...

Background The incidence of inflammatory bowel disease (IBD) continues to rise worldwide. Despite the advances on pharmacotherapy, the etiopathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) remains underexplained. The migratory waves are a challenging setting to analyze the evolution of IBD prevalence and to infer its triggering facto...

Background: Several potassium channels (KCs) have been described throughout the gastrointestinal tract. Notwithstanding, their contribution to both physiologic and pathophysiologic conditions, as inflammatory bowel disease (IBD), remains underexplored. Therefore, we aim to systematically review, for the first time, the evidence on the characterist...

Background The roles dipeptidyl peptidase 4 (DPP4), aminopeptidase N (APN), and their substrates in autoimmune diseases are being increasingly recognized. However, their significance in inflammatory bowel diseases (IBD) is not entirely understood. This systematic review aims to discuss the pathophysiological processes related to these ectopeptidase...

Background The incidence of inflammatory bowel disease (IBD) continues to rise worldwide and despite the advances on pharmacotherapy, the etiopathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) remains underexplained. In this context, the migratory waves of the last decades created a challenging setting to analyze the evolution of IBD...

Background and Aims Therapeutic drug monitoring (TDM) of infliximab (IFX) and anti-infliximab antibodies (ATIs) is essential for treatment optimisation in inflammatory bowel disease (IBD) patients. The aim of this study was to estimate and compare the agreement and accuracy between a new rapid test and three established enzyme-linked immunosorbent...

Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it...