Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA.

BACKGROUND & AIMS: The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. METHODS: We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish ENEIDA registry. Data extraction was conducted in July 2021. RESULTS: A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17-40 y) (relative risk ratio, 1.45; 95% CI, 1.31-1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38-1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14-1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07-1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38-1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79-0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70-0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71-0.82), and complications (odds ratio, 0.73; 95% CI, 0.66-0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26-1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66-0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67-0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55-0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69-0.88). CONCLUSIONS: There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.

HIV infection is associated with a less aggressive phenotype of inflammatory bowel disease. A multicenter study of the ENEIDA registry.

BACKGROUND: The coexistence of human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management is scarce. AIM: To describe the IBD phenotype, therapeutic requirements and prevalence of opportunistic infections (OI) in IBD patients with a coexistent HIV infection. METHODS: Case-control, retrospective study including all HIV positive patients diagnosed with IBD in the ENEIDA registry. Patients with positive HIV serology (HIV-IBD) were compared to controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD. RESULTS: A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis (UC), 35% had Crohn's disease (CD) and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in UC and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, non-biological therapies (37.4% vs. 57.9%; P=0.001) and biologicals (26.4% vs. 42.1%; P=0.007), were used less frequently among patients in the HIV-IBD group. Conversely, HIV-IBD patients developed more OI than controls regardless of non-biological therapies use. In the multivariate analysis, HIV infection (OR 4.765, 95%CI 2.48-9.14; P<0.001) and having ≥1 comorbidity (OR 2.445, 95%CI 1.23-4.85; P=0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95%CI 0.18-0.78;P=0.009). CONCLUSIONS: HIV infection appears to be associated with a less aggressive phenotype of IBD and a lesser use of non-biological therapies and biologicals but entails a greater risk of developing OI.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

BACKGROUND AND AIMS: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era. METHODS: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes. RESULTS: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC. CONCLUSIONS: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

High incidence of surgery and initiation of medical therapies after colectomy for ulcerative colitis or inflammatory bowel disease unclassified.

BACKGROUND AND AIMS: Despite novel medical therapies, colectomy has a role in the management of patients with ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU). This study aimed to determine the incidence of unplanned surgery and initiation of immunomodulatory or biologic therapy (IMBT) after colectomy in patients with UC or IBDU, and identify associated factors. METHODS: Data of patients with preoperative diagnosis of UC or IBDU who underwent colectomy and were followed up at a single tertiary centre was retrospectively collected. The primary outcome was the risk of unplanned surgery and initiation of IMBT during follow-up after colectomy. Secondary outcomes were development of Crohn's disease-like (CDL) complications and failure of reconstructive techniques. RESULTS: 68 patients were included. After a median follow-up of 9.9 years, 32.4% of patients underwent unplanned surgery and IMBT was started in 38.2%. Unplanned surgery-free survival was 85% (95% confidence interval [CI] 73.8-91.6%) at 1 year, 76% (95% CI 63.2-84.9%) at 5 years and 69.1% (95% CI 55-79.6%) at 10 years. IMBT-free survival was 96.9% (95% CI 88.2-99.2%) at 1 year, 77.6% (95% CI 64.5-86.3%) at 5 years and 63.3% (95% CI 48.8-74.7%) at 10 years. 29.4% of patients met criteria for CDL complications. CDL complications were significantly associated to IMBT (hazard ratio 4.5, 95% CI 2-10.1). CONCLUSION: In a retrospective study, we found a high incidence of unplanned surgery and IMBT therapy initiation after colectomy among patients with UC or IBDU. These results further question the historical concept of surgery as a "definitive" treatment.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy.

BACKGROUND: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

Polypharmacy in Patients With Inflammatory Bowel Disease: Prevalence and Outcomes in a Single-center Series.

BACKGROUND: Polypharmacy can complicate the course and management of chronic diseases, and has been little explored in patients with inflammatory bowel disease (IBD) to date. AIM: The aim of this study was to determine the prevalence of polypharmacy in a series of IBD patients, describing associated factors and its correlation with poor disease outcomes. MATERIALS AND METHODS: Retrospective study of a single-center series. Polypharmacy was defined as the simultaneous use of 5 or more drugs. Disease outcomes, IBD treatment nonadherence and undertreatment were evaluated at 1 year. RESULTS: A total of 407 patients were included [56% males, median age: 48 y (interquartile range, 18 to 92 y)], of whom 60.2% had Crohn's disease; Chronic comorbidity and multiple comorbidities were present in 54% and 27% of patients, respectively. Median number of prescriptions per patient was 3 (range: 0 to 15). Polypharmacy was identified in 18.4% of cases, inappropriate medication in 10.5% and use of high-risk drugs in 6.1% (mainly opioids). In multivariate analysis, polypharmacy was associated with chronic comorbidity [odds ratio (OR)=10.1, 95% confidence interval (CI): 2.14-47.56; P˂0.003], multiple comorbidities (OR=3.53, 95% CI: 1.46-8.51; P=0.005) and age above 62 years (OR=3.54, 95% CI: 1.67-7.51; P=0.001). No association with poor disease outcomes was found at 12 months. However, polypharmacy was the only factor associated with IBD treatment nonadherence (OR=2.24, 95% CI: 1.13-4.54, P=0.02). CONCLUSIONS: Polypharmacy occurs in around 1 in 5 patients with IBD, mainly in older adults and those with comorbidity. This situation could interfere with adherence to IBD treatment and therapeutic success.

Self-medication with analgesics reported by patients with ulcerative colitis: An anonymous survey.

INTRODUCTION: Analgesics are widely used, but evidence regarding whether their use increases the risk of inflammatory bowel disease (IBD) flares or complications is unclear. Therefore, self-medication with analgesics in IBD is usually not recommended. The aim of this study was to explore the prevalence of self-medication with analgesics in a cohort of ulcerative colitis (UC) patients and to identify reasons and factors associated with self-medication. METHODS: This cross-sectional study included consecutive unselected adult patients with UC. Participants were asked to complete an anonymous web-based survey with multiple-choice questions and closed responses. No clinical data were collected. RESULTS: A total of 546 patients (61.2% women, mean age 39.9 years) completed the survey. The prevalence of self-medication with analgesics was 49.8% (272/546). Paracetamol (45.2%) and metamizole (21.2%) were the most frequently used drugs; frequencies of self-medication were <5% for other analgesics (nonsteroidal anti-inflammatory drugs, opioids). The most frequent reasons for self-medication were the need for quick symptom relief and that it had been agreed with/prescribed by the treating physician. Multivariable analysis identified female sex (odds ratio [OR]=1.9), sick leave (OR=2.2), treatment with intravenous drugs (OR=2.9), and emergency room visit (OR=2.3) as variables associated with self-medication, whilst follow-up by a nurse was associated with less self-medication (OR=0.6). CONCLUSION: The frequency of self-medication with analgesics in UC patients is high and appears to be associated with variables suggesting worse disease control. Closer follow-up, including a specialized nurse, could decrease self-medication. Strategies to improve disease control, including close monitoring of symptoms such as pain, are needed.

Onset of ulcerative colitis and complete response during the treatment of a metastatic colon cancer: case report and literature review.

Colorectal cancer is a common cancer worldwide. Several risk factors have been described, such as age, lifestyle and family history. Inflammatory bowel diseases (IBD) are a well-recognized risk factor for the development of colorectal cancer. However, the onset of an IBD de novo in the context of the treatment of a colorectal neoplasia has not been reported before, except in the context of the treatment with immunocheckpoint inhibitors. Fifty-nine-years old man diagnosed with a metastatic colorectal cancer who received conventional treatment with chemotherapy and an antiangiogenic inhibitor. The patient had a complete response with the therapy after few cycles. Nevertheless, during the treatment, the patient presented with rectal bleeding, and was diagnosed with ulcerative colitis. Although the treatment was discontinued, tumoral complete remission is maintained. The relevance of this case lies in the concurrence of the onset of an autoimmune disease and a complete response of the malignancy. The concurrence of these events has been described previously only with immunotherapy. There are not cases reported involving chemotherapy and antiangiogenic drugs. Other causes of colitis were ruled out due to the unusual presentation of the case.

Extraintestinal Manifestations in Patients with Inflammatory Bowel Disease: Study Based on the ENEIDA Registry.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others. AIMS: Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date. METHODS: Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018. RESULTS: The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease, p < 0.001), gender (female, p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs. CONCLUSIONS: One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Idiopathic acute pancreatitis in patients with inflammatory bowel disease: A multicenter cohort study.

BACKGROUND: Idiopathic acute pancreatitis (IAP) in patients with inflammatory bowel disease (IBD) is not well characterized. Our purpose was to better understand this condition and its natural history. METHODS: Retrospective cohort study conducted at nine Spanish IBD referral centers. Patients with IBD and a first episode of acute pancreatitis (AP) between 1998 and 2018 were included. Patients with a previous episode of AP or a diagnosis of chronic pancreatitis were excluded. IAP and non-IAP were compared by multivariate logistic regression and survival analysis. RESULTS: We identified 185 patients with IBD (68.7% Crohn's disease) and a first episode of AP. Thirty-eight of those 185 (20.6%) fulfilled criteria for IAP. There were no severe cases of IAP. On multivariate analysis, AP before IBD diagnosis (21.1% vs. 3.4%, p = 0.04) and ulcerative colitis (52.6% vs. 23.1%, p = 0.002) were significantly more common in IAP. Further work-up was performed in 16/38 (42%) IAP patients, and a cause was identified in 6/16 (37.5%). Median time from AP to the end of follow-up was 6.3 years (3.1-10). Five-year risk of AP recurrence was significantly higher in IAP group (28% vs. 5.1%, log-rank p = 0.001), with a median time to first recurrence of 4.4 months (2.9-12.2). CONCLUSIONS: IAP represents the second cause of AP in patients with IBD. It is more frequent in ulcerative colitis, and presents a high risk of recurrence. Additional imaging work-up after a first episode of IAP in IBD patients is highly advisable, as it identifies a cause in more than one-third of cases.

Spacing the Administration Interval of Anti-TNF Agents: A Valid Strategy for Patients with Inflammatory Bowel Disease?

BACKGROUND: Increasing the interval of administration of anti-TNF agents over the duration specified in the data sheet is not common in inflammatory bowel disease (IBD). AIM: To evaluate the outcomes of IBD patients treated with this strategy. METHODS: Patients with IBD who were treated with infliximab or adalimumab at intervals > 8 weeks or > 2 weeks, respectively, because of persistent clinical remission, were identified at local databases of the ENEIDA registry (a nationwide registry promoted by the Spanish Working Group in Crohn's disease and Ulcerative Colitis-GETECCU) of two referral centers. Treatment success was considered if patients remained in clinical remission with the same schedule or without biological therapy at the end of follow-up, and if no return to the conventional schedule, dose-escalation, change in biological agent, or a course of systemic corticosteroids or surgery were required. RESULTS: Eighty-five patients were included, 60 treated with infliximab and 25 with adalimumab. The spaced schedule was initiated after a median of 25 months on anti-TNF treatment (IQR 14-49). Throughout a median follow-up of 34 months (IQR 21-47), fifty patients (59%) fulfilled the success criteria of the spaced strategy. No differences were found regarding type of IBD or anti-TNF agent. Baseline C-reactive protein levels and disease duration at the time of starting anti-TNF treatment were the only factors associated with treatment success. CONCLUSIONS: Anti-TNF administration at longer intervals than those provided in the data sheet may be an efficacious, convenient, and cheaper treatment option, particularly in patients in whom anti-TNF treatment was initiated early.

Nivolumab-induced immune-mediated colitis: an ulcerative colitis look-alike-report of new cases and review of the literature.

PURPOSE: Nivolumab, a monoclonal antibody-targeting programmed cell death protein-1, is being increasingly used for the treatment of some advanced neoplasms. Several of its adverse effects are a result of the upregulation of T cells, with colitis as one of the most severe, and a challenging differential diagnosis with ulcerative colitis. However, few real-life clinical practice cases have been reported beyond trials. Our aim was to report a series of new cases, reviewing previously communicated endoscopic-proven nivolumab-induced colitis. METHOD: All patients treated with nivolumab in three university centers were identified and those who developed immune-mediated colitis (defined as the presence of diarrhea and evidence of colitis demonstrated by colonoscopy) were described. Additionally, a review of case reports of nivolumab-induced colitis reported in the literature up to March 2018 was performed. RESULTS: Six new cases of nivolumab-induced colitis and 13 previously reported cases out of randomized clinical trials are described. Colonoscopy showed a mucosal pattern mimicking ulcerative colitis in a large proportion of patients. Clostridium difficile superinfection was observed in two out of 19 cases. All but three patients definitively discontinued nivolumab therapy. Most patients were initially managed with oral or intravenous corticosteroids, but five of them required rescue therapy with infliximab. CONCLUSIONS: Nivolumab-induced colitis may mimic ulcerative colitis. Steroid therapy (oral or intravenously) is often efficient, but one-fourth of patients need rescue therapy with anti-TNF. Intestinal superinfection with Clostridium difficile or cytomegalovirus should be ruled out before starting immunosuppressive therapy.

Autologous haematopoietic stem cell transplantation in refractory Crohn's disease: Experience in our centre. / Trasplante de precursores hematopoyéticos en enfermedad de Crohn refractaria: experiencia en nuestro centro.

INTRODUCTION: Autologous haematopoietic stem cell transplantation (AHSCT) is an accepted treatment in refractory Crohn's disease (CD). MATERIAL AND METHODS: Data on patients with refractory CD subjected to AHSCT are collected at the Hospital Universitario Ramón y Cajal in Madrid and the results obtained are described retrospectively. RESULTS: Seven patients in total have received AHSCT due to refractory CD in our centre. Three patients (43%) presented with clinical and endoscopic remission; one patient (14%) clinical improvement without remission and three patients (43%) remained active with the need to restart treatment in the assessment of the initial response to the AHSCT (after six months). Symptoms recurred in five of the seven patients (71%) and all of them had to restart medical treatment after an average of 13.8 months (range: 3-30 months). Only one patient needed surgery after the AHSCT. At the end of the follow-up, after a mean of 48 months (range: 17-78 months), 5/7 (71%) of the patients were in clinical remission with or without treatment. CONCLUSION: AHSCT may be a promising therapeutic option for patients with refractory CD. Its usefulness lies in the fact that it can produce clinical remission without treatment in some patients, but also that it can make the disease treatable, obtaining a response to certain treatments in patients who had previously lost it.

Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: The SportDiet study.

Obesity increases the risk of clinical decompensation in cirrhosis, possibly by increasing portal pressure. Whether weight reduction can be safely achieved through lifestyle (LS) changes (diet and exercise) in overweight/obese patients with cirrhosis, and if weight loss reduces portal pressure in this setting, is unknown. This prospective, multicentric, uncontrolled pilot study enrolled patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mm Hg), and body mass index (BMI) ≥26 kg/m2 in an intensive 16-week LS intervention program (personalized hypocaloric normoproteic diet and 60 min/wk of supervised physical activity). We measured HVPG, body weight (BW) and composition, adipokines, health-related quality of life, and safety data before and after the intervention. Changes in HVPG and BW were predefined as clinically relevant if ≥10% and ≥5%, respectively. Safety and BW were reassessed after 6 months. 60 patients were included and 50 completed the study (56 ± 8 years old; 62% male; nonalcoholic steatohepatitis etiology 24%; BMI 33.3 ± 3.2 kg/m2 ; Child A 92%; HVPG ≥10 mm Hg, 72%). LS intervention significantly decreased BW (average, -5.0 ± 4.0 kg; P < 0.0001), by ≥5% in 52% and ≥10% in 16%. HVPG also significantly decreased (from 13.9 ± 5.6 to 12.3 ± 5.2 mm Hg; P < 0.0001), by ≥10% in 42% and ≥20% in 24%. A ≥10% BW loss was associated with a greater decrease in HVPG (-23.7 ± 19.9% vs. -8.2 ± 16.6%; P = 0.024). No episodes of clinical decompensation occurred. Weight loss achieved at 16 weeks was maintained at 6 months; Child and Model for End-Stage Liver Disease scores did not change. CONCLUSION: Sixteen weeks of diet and moderate exercise were safe and reduced BW and portal pressure in overweight/obese patients with cirrhosis and portal hypertension. (Hepatology 2017;65:1293-1305).

[Ipilimumab-induced colitis: A new challenge for gastroenterologists]. / Colitis secundaria a ipilimumab: un nuevo reto para el gastroenterólogo.

Many drugs can produce enterocolitis and they should always be included in the differential diagnosis of this clinical picture. Entities such as antibiotic-associated colitis and neutropenic colitis have been known for some time and recently a new type of drug-induced colitis has emerged due to monoclonal antibodies. Ipimumab is a humanized monoclonal antibody against the CTLA4 molecule that is involved in the maturation and regulation of T lymphocyte activation. This drug causes immune activation and has an immune-mediated antitumor effect with excellent results in tumours such as melanoma. However, several immune-related adverse effects may occur in different organs. The most frequently involved site is the gastrointestinal tract, with adverse effects ranging from mild diarrhoea to colitis with systemic involvement, intestinal perforation, and even death. Although no similarities have been found in the pathogenesis with inflammatory bowel disease, treatments have been used in correlation with its autoimmunological profile: anti-TNF alpha corticosteroids have shown clinical efficacy in moderate to severe disease. However the use of anti-TNF treatment has not been defined and the safety profile is unknown. The inclusion of these new therapies in the treatment of several tumours requires familiarity with these entities and their management should be approached as a new challenge for the gastroenterologist. For that reason, we conducted a review of ipilimumab-induced colitis, evaluating essential features of its symptoms, diagnosis and treatment.