Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort.

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

MicroRNA and granulocyte-monocyte adsorption apheresis combotherapy after inadequate response to anti-TNF agents in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, affecting millions of individuals throughout the world, and producing an impaired health-related quality of life. Granulocyte and monocyte apheresis (GMA) is a therapeutic option for UC management to induce remission by selective removal of activated leukocytes from bloodstream. Despite the knowledge of the important role of epigenetics in UC pathogenesis, and in the response to different treatments, nothing is known about the role of microRNAs in GMA therapy in UC patients. METHODS: Seven consecutively UC patients who started GMA in combo therapy with infliximab were recruited. Peripheral blood samples were taken before the apheresis session, at the start of the induction (S0) and at the end (S10). They were follow-up during the induction phase (10 sessions: 2 sessions for a week during 3 wk and 1 session for a week during 4 wk) of the treatment at a tertiary hospital (Hospital la Fe) and 6 mo after finishing the GMA induction therapy. MiRNA was extracted and analyzed by RT-PCR. R software and GraphPad were used. RESULTS: Clinical disease activity significantly decreased after induction therapy with GMA (median partial Mayo score 2 (IQR, 1-6) (P < .05). Fecal calprotectin value and CRP value significantly decreased after induction therapy. Five microRNAs modified their expression during GMA (unsupervised analysis): miR-342-3p, miR-215-5p, miR-376c-3p, miR-139-5p, and miR-150-5p. When a sub-analysis was performed in those patients who showed good response to apheresis treatment (n = 5), two microRNAs showed to be implicated: miR-215-5p and miR-365a-3p. These are preliminary but promising and novel results, as it is the first time, to our knowledge that microRNA profiles have been studied in the context of GMA treatment for IBD.

Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine.

BACKGROUND: Thiopurines such as azathioprine (AZA) and mercaptopurine (MP) are commonly utilized to treat inflammatory bowel disease (IBD). Their use is frequently restricted due to gastrointestinal intolerance (GI). Previous retrospective studies have reported that AZA-intolerant patients may benefit from a switch to MP; yet the effectiveness of this strategy has not been prospectively evaluated. AIMS: To assess GI tolerance to MP in patients who are intolerant to AZA, and to identify clinical predictors of GI intolerance to AZA or MP. METHODS: A prospective, observational, single-cohort study was performed in 92 thiopurine-naïve IBD patients. They were started on a 50mg dose of AZA and escalated to 2.5mg/kg per day by week 2. Those with GI intolerance were rechallenged with a 50% dose of AZA, after which another dose escalation attempt was made. If symptoms persisted, they were switched to MP. RESULTS: Thirty (32.6%) of the recruited patients suffered from GI intolerance to AZA. Of these, 15 did not present recurrence of symptoms after rechallenge with lower doses. Of 15 intolerant patients, 14 were switched to MP. Within the MP cohort, 8 patients (57%) were also intolerant to MP, 5 (36%) had no symptoms, and 1 (7%) was lost to follow-up. Female gender was the only independent predictor of GI intolerance to AZA. CONCLUSIONS: Up to half of the AZA-intolerant patients tolerated a 50% dose rechallenge that was successfully escalated. A switch to MP was tolerated in over a third of cases whom rechallenge failed. Our strategy (challenge-rechallenge-switch) achieved an overall GI tolerance to thiopurines in most of the patients.

Recommendations of the Valencian Society of Digestive Pathology for the use of telemedicine and non-contact consultations. / Recomendaciones de la Sociedad Valenciana de Patología Digestiva sobre uso de consultas no presenciales y telemedicina.

The COVID-19 pandemic has meant a qualitative change in the way patients are treated in outpatient clinics. The need to take measures of social isolation as prevention for contagion by the new coronavirus has forced the use of telematic and telephone consultations in most medical and surgical units. The specialty of digestive medicine, due to the characteristics of its patients and frequent support in complementary techniques for diagnosis, is especially suitable for the use of non-contact consultations. In this document a series of recommendations are proposed that can serve as a guide for the establishment or improvement of non-face-to-face digestive medicine consultations.

Changes in the management of IBD patients since the onset of COVID-19 pandemic. A path toward the implementation of telemedicine in Spain?

BACKGROUND: COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as inflammatory bowel disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice. METHODS: This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients. RESULTS: We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51.3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely. CONCLUSIONS: Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals' and patients' requirements.

The characteristics of the stricture, but not the ongoing treatment, could influence the outcome of endoscopic dilation in recurrent Crohn's disease.

AIM: Stricture is one of the main complications of Crohn's disease (CD). Among the main conservative therapeutic alternatives, endoscopic balloon dilation (EBD) of the strictures stands out, which can improve the symptoms and delay or even avoid the need for more surgeries. The main aim of this study was to evaluate the efficacy of the EBD in CD patients with post-surgical anastomotic strictures from a previous surgery. PATIENTS AND METHODS: An observational study of a cohort of 32 patients with CD who underwent EBD due to uncomplicated strictures at a tertiary hospital, since 2009. Demographic, clinical and disease variables, medical treatments and previous surgeries and types, analytical variables at the time of dilation, number of dilations, complications and need for subsequent surgery were collected by searching data in clinical records. RESULTS: Thirty-two patients were included, performing a total of 63 endoscopic dilations. A technical success of 63.5%, a therapeutic success by dilation of 58.75% and a therapeutic success per patient of 62.5% were achieved. Regarding complications, the percentage of post-dilation adverse events was 3.2% and post-dilation incidents were 4.8%. Thirty EBD did not need any medical treatment modification, 9 EBD remained untreated and 12 EBD required further surgery. The length of the strictures, but not the ongoing treatment, was the only statistically significant factor of therapeutic success by dilation and per patient. CONCLUSIONS: EBD seems a safe technique in short post-surgical strictures, can avoid the need for new surgery and prevents unnecessary immunosuppression in patients with CD anastomotic strictures.

Evolution of the emotional impact in patients with early inflammatory bowel disease during and after Covid-19 lockdown.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD. METHODS: This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2-5.4) and IBD activity (4.3; 1.8-10.4). Factors related to depression were comorbidity (3.3; 1.1-9.8), IBD activity (6; 1.9-18.1), use of biologics (2.9; 1.1-7.6), and living alone or with one person (3.1; 1.2-8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01-6.3), Crohn's disease (3.3; 1.3-8.5), and active IBD (4.1; 1.2-13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6-24.9), active IBD (7.5; 2.1-26.8), and steroid use (6.4; 1.4-29). CONCLUSIONS: Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.

Risk of infection associated with Janus Kinase (JAK) inhibitors and biological therapies in inflammatory intestinal disease and rheumatoid arthritis. Prevention strategies. / Riesgo de infección asociado a los inhibidores de las quinasas Janus (JAK) y las terapias biológicas en enfermedad inflamatoria intestinal y artritis reumatoide. Estrategias de prevención.

Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive. These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.

The Harvey-Bradshaw Index Adapted to a Mobile Application Compared with In-Clinic Assessment: The MediCrohn Study.

Objectives: Mobile apps are useful tools in e-health and self-management strategies in disease monitoring. We evaluated the Harvey-Bradshaw index (HBI) mobile app self-administered by the patient to see if its results agreed with HBI in-clinic assessed by a physician. Methods: Patients were enrolled in a 4-month prospective study with clinical assessments at months 1 and 4. Patients completed mobile app HBI and within 48 h, HBI was performed by a physician (gold standard). HBI scores characterized Crohn's disease (CD) as remission <5 or active ≥5. We determined agreement per item and total HBI score and intraclass correlation coefficients (ICCs). Bland-Altman plot was performed. HBI changes in disease activity from month 1 to month 4 were determined. Results: A total of 219 patients were enrolled. All scheduled assessments (385 pairs of the HBI questionnaire) showed a high percentage of agreement for remission/activity (92.4%, κ = 0.796), positive predictive value (PPV) for remission of 98.2%, and negative predictive value of 76.7%. High agreement was also found at month 1 (93.15%, κ = 0.82) and month 4 (91.5%, κ = 0.75). Bland-Altman plot was more uniform when the HBI mean values were <5 (remission). ICC values were 0.82, 0.897, and 0.879 in all scheduled assessments, 1 and 4 months, respectively. Conclusions: We found a high percentage of agreement between patients' self-administered mobile app HBI and in-clinic physician assessment to detect CD activity with a remarkably high PPV for remission. The mobile app HBI might allow a strict control of inflammation by remote monitoring and flexible follow-up of CD patients. Reduction of sanitary costs could be possible.

Telemonitoring of Crohn's Disease and Ulcerative Colitis (TECCU): Cost-Effectiveness Analysis.

BACKGROUND: Although electronic health interventions are considered safe and efficient, evidence regarding the cost-effectiveness of telemonitoring in inflammatory bowel disease is lacking. OBJECTIVE: We aimed to evaluate the cost-effectiveness and cost-utility of the Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa (Telemonitoring of Crohn's Disease and Ulcerative Colitis [TECCU]) Web platform (G_TECCU intervention group) for telemonitoring complex inflammatory bowel disease, compared with standard care (G_control) and nurse-assisted telephone care (G_NT intervention group). METHODS: We analyzed cost-effectiveness from a societal perspective by comparing the 3 follow-up methods used in a previous 24-week randomized controlled trial, conducted at a tertiary university hospital in Spain. Patients with inflammatory bowel disease who initiated immunosuppressants or biologic agents, or both, to control inflammatory activity were recruited consecutively. Data on the effects on disease activity (using clinical indexes) and quality-adjusted life-years (using the EuroQol 5 dimensions questionnaire) were collected. We calculated the costs of health care, equipment, and patients' productivity and social activity impairment. We compared the mean costs per patient, utilities, and bootstrapped differences. RESULTS: We included 63 patients (21 patients per group). TECCU saved €1005 (US $1100) per additional patient in remission compared with G_control (95% CI €-13,518 to 3137; US $-14,798 to 3434), with a 79.96% probability of being more effective at lower costs. Compared with G_NT, TECCU saved €2250 (US $2463) per additional patient in remission (95% CI €-15,363 to 11,086; US $-16,817 to 12,135), and G_NT saved €538 (US $589) compared with G_control (95% CI €-6475 to 5303; US $-7088 to 5805). G_TECCU and G_NT showed an 84% and 67% probability, respectively, of producing a cost saving per additional quality-adjusted life-year (QALY) compared with G_control, considering those simulations that involved negative incremental QALYs as well. CONCLUSIONS: There is a high probability that the TECCU Web platform is more cost-effective than standard and telephone care in the short term. Further research considering larger cohorts and longer time horizons is required. TRIAL REGISTRATION: ClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (http://www. webcitation.org/746CRRtDN).

Adsorptive granulocyte/monocyte apheresis use in severe ulcerative colitis and determination of changes in plasma cytokines.

Despite controversy regarding the use of granulocyte/monocyte adsorption (GMA) in inflammatory bowel disease, some studies have shown favorable outcomes when it is used in steroid-dependent patients with ulcerative colitis (UC). The mechanisms responsible for such outcomes are not well characterized, but changes in immune cell populations and cytokine levels have been suggested to play an important role. We report the cases of 3 patients with chronically active severe UC who underwent GMA due to an inadequate response to standard and rescue therapy, as well as changes to their plasma cytokine profile. All the patients presented severe UC that was only partially responsive to various immunosuppressive drugs, and they were, therefore, referred for colectomy; however, all 3 refused this option, which led to the compassionate use of GMA as a last therapeutic resort. Following GMA treatment, rapid normalization of the clinical, endoscopic and laboratory parameters was observed in all the patients. Despite having achieved a good response, most cytokines remained at high concentrations after GMA, and only two, IL-6 and IL-8, showed a clear decrease throughout the GMA sessions. In view of this outcome, we hypothesize that GMA can help to lower the inflammatory load, thereby enhancing the effect of biologic drugs. To confirm this hypothesis and explore further indications for GMA, we propose the need for research directed toward the characterization of immune cell populations and their specific cytokine production rather than global cytokine assessment.

A Web-Based Telemanagement System for Improving Disease Activity and Quality of Life in Patients With Complex Inflammatory Bowel Disease: Pilot Randomized Controlled Trial.

BACKGROUND: The reported efficacy of telemedicine in patients with inflammatory bowel disease (IBD) is inconsistent among studies, and data for complex IBD are lacking. OBJECTIVE: We aimed to evaluate the impact of remote monitoring using a Web system-Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa or Telemonitoring of Crohn's Disease and Ulcerative Colitis (TECCU)-as compared to standard care and telephone care on health outcomes and health care in patients with complex IBD. METHODS: We performed a 3-arm randomized controlled trial. Adult patients with IBD who received immunosuppressants and biological agents were recruited from the IBD Unit of a tertiary university hospital. The patients were randomized into groups to receive remote monitoring (G_TECCU), nurse-assisted telephone care (G_NT), or standard care with in-person visits (G_control). All patients completed the study visits at baseline and at 12 and 24 weeks in addition to each type of intervention. The primary outcome was the percentage of patients in remission at 24 weeks. Secondary health outcomes were quality of life, medication adherence, adverse effects, satisfaction, and social activities. Data on the number of outpatient visits and telephone calls, emergency visits, hospitalizations, IBD-related surgeries, and corticosteroid courses were also collected. RESULTS: A total of 63 patients were selected (21 patients in each group). During the study, 90.5% (19/21) of patients in G_control, 95.2% (20/21) in G_NT, and 85.7% (18/21) in G_TECCU were compliant to the intervention. After 24 weeks, the percentage of patients in remission was higher in G_TECCU (17/21, 81%) than in G_NT (14/21, 66.7%) and G_control (15/21, 71.4%). A higher improvement in disease activity was observed in G_TECCU than in G_control in terms of the Harvey-Bradshaw/Mayo (odds ratio=0.12, 95% CI=0.003-2.162, P=.19) and Harvey-Bradshaw/Walmsley (odds ratio=0.11, 95% CI=0.004-1.55, P=.13) indexes. Improvement in disease activity was associated with a larger reduction in fecal calprotectin values in G_TECCU compared to G_control (estimated intervention effect: odds ratio=-0.90; 95% CI=-1.96 to 0.16, P=.11). All completers adhered to treatment in G_TECCU. In addition, the quality of life, social activities, and satisfaction improved in all 3 groups. Although the number of outpatient visits and telephone calls was lower in G_TECCU than in G_NT and G_control, the safety profile was similar in all 3 groups. CONCLUSIONS: This pilot clinical trial suggests that the TECCU Web-based system is a safe strategy for improving health outcomes in patients with complex IBD and reducing the use of health care resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (Archived by WebCite at http://www.webcitation.org/746CRRtDN).

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of thiopurines in inflammatory bowel disease. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el uso de tiopurinas en la enfermedad inflamatoria intestinal.

Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding.

Telemedicine in the treatment of patients with inflammatory bowel disease. / Telemedicina en el manejo de pacientes con enfermedad inflamatoria intestinal.

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder with significant medical, social and financial impacts. IBD patients require continuous follow-up, and healthcare resource use in this context increases over time. In the last decade, telemedicine has influenced the treatment of chronic diseases like IBD via the application of information and communication technologies to provide healthcare services remotely. Telemedicine and its various applications (telemanagement, teleconsulting and tele-education) enable closer follow-up and provide education resources that promote patient empowerment, encouraging treatment optimisation over the entire course of the disease. We describe the impact of using telemedicine on IBD health outcomes and discuss the limitations of implementing these systems in the real-life management of IBD patients.

A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.

The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1525 healthy controls from Spain with the six previously published GWAS comprising 6687 cases and 19 718 controls from Northern-European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 [rs2858829, P = 8.97 × 10(-9), odds ratio (OR) (95% confidence interval, CI] = 1.12 (1.08-1.16)] that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1073 cases and 1279 controls [combined P = 7.59 × 10(-10), OR (95% CI) = 1.12 (1.08-1.16)]. Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P < 0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.

Psychological burden and quality of life in newly diagnosed inflammatory bowel disease patients.

Objective: Psychological factors, such as stress, anxiety, and depression, are frequently related to inflammatory bowel disease (IBD). However, few studies have examined these factors in patients newly diagnosed with IBD. The aim of the present study was to test the psychological burden in patients with a recent diagnosis of IBD and the factors related to this psychological burden. Methods: We performed a prospective, multi-center, observational study in patients with a new diagnosis of IBD (≤6 months). The patients were recruited from four different Spanish hospitals. Clinical and demographic characteristics were collected. Patients were evaluated using the Hospital Anxiety and Depression Scale and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ-32). The Scale of Stress Perceived by the Disease was used to assess stressful life events. Results: We included 156 patients newly diagnosed with IBD [69 women; 80 Crohn's disease (CD) and 76 ulcerative colitis (UC)], with a mean age of 42.3 (SD 16.21) years. A total of 37.2% of patients had symptoms of anxiety and 17.3% had symptoms of depression. Quality of life was affected in 30.1% of patients. Factors related to anxiety in early IBD were being a woman and having CD. The only factor related to depression was the presence of comorbidity. Being a woman and having suffered previous stressful life events were factors related to impaired quality of life. Conclusion: Anxiety, depression, and impaired quality of life are frequent in patients with a recent diagnosis of IBD. This psychological burden is greater in women.

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

BACKGROUND: The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. AIMS: To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. METHODS: Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. RESULTS: Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. CONCLUSION: Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.