Long-term outcome in patients with ulcerative colitis treated with intravenous cyclosporine A is determined by previous exposure to thiopurines

Background and aimRescue therapy with intravenous cyclosporine A (CsA) helps to avoid colectomy in a substantial proportion of patients with severe ulcerative colitis (UC) but the impact on long-term outcome remains unclear. Therefore, we aimed to define predictive factors for colectomy in patients treated with intravenous CsA for severely active UC.MethodsA retrospective, single-center study with a minimum follow-up of 18 months was performed.ResultsA total of 64 patients were evaluable (median age 33 years [range 17–80 years], female 54.7%). Median intravenous CsA dose was 4 mg/kg/day (range 2–5 mg/kg/day). After a median follow-up of 65 months (range 2–160 months), 19 patients (29.7%) underwent colectomy, 15 within 18 months. Of the various baseline parameters tested, only previous non-response to thiopurine treatment (p = 0.006) was associated with an increased risk of colectomy. During 18 months follow-up, thiopurine-naïve patients receiving thiopurine maintenance therapy after intravenous CsA (32/64, 50.0%) underwent colectomy in 12.5% of cases. The colectomy rate was 27.3% among 22 patients previously non-responsive to thiopurines who continued treatment after intravenous CsA, compared to 50.0% in the 10 patients who discontinued thiopurines prior to intravenous CsA or who never received thiopurines (p = 0.037).ConclusionsThe long-term colectomy rate after intravenous CsA in patients with severely active UC was relatively low in our series compared to the literature. Concomitant treatment with thiopurines was the only predictor for a reduced risk of colectomy.     

Caracterización y prevalencia de manifestaciones extraintestinales en una cohorte de pacientes con enfermedad inflamatoria intestinal en Medellín (Colombia)

IntroductionExtraintestinal manifestations (EIMs) are frequent in patients with inflammatory bowel disease (IBD). Our objective is to characterize and determine the prevalence of MEIs in our cohort of patients with IBD.Patients and methodsA retrospective study was carried out in adult patients with IBD at the Pablo Tobón Uribe Hospital in Medellín. Colombia. Articular MEIs, primary sclerosing cholangitis (PSC), both ophthalmological and dermatological, were considered. Absolute and relative frequencies were used. The Chi square test of independence was used to compare 2 proportions and the odds ratio (OR) was estimated.ResultsOur registry has 759 patients with IBD, 544 present UC (71.6%), 200 CD (26.3%) and 15 unclassifiable IBD (1.9%); 177 patients with IBD (23.3%) presented EIMs, 123 of 544 (22.6%) with UC and 53 of 200 (26.5%) with CD (OR: 0.81, 95% CI: 0.55-1.17, P = 0.31). Regarding the type of EIMs, the articular ones were the most frequent (13.5%), more in CD than in UC (20.0 vs. 11.3%, OR 1.94, 95% CI: 1.25-3.00, P = 0.0037). Patients with IBD and EIMs used more antibodies against tumor necrosis factor (anti-TNFs), compared to those without EIMs (43.5 vs. 18.5%, OR 3.38, 95% CI: 2.31-4.90, P = 0.0001).ConclusionsThe prevalence of EIMs in our cohort is high (23.3%) and the most frequent type is joint. Anti-TNFs are most used when IBD and EIMs coexist. Our study provides valuable information on the association of EIMs and IBD in Latin America.     

Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative colitis: Early and long-term data from a retrospective observational study

IntroductionAbout 30-40% of patients with acute severe ulcerative colitis (UC) fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv cyclosporine and infliximab are an effective rescue therapy in steroid-refractory UC patients but up to now it is still unclear which is the best therapeutic choice.MethodsWe reviewed our series of severe steroid-refractory colitis admitted consecutively since 1994 comparing two historical cohort treated with iv cyclosporine (2 mg/kg) or iv infliximab (5 mg/kg). The main outcome was the colectomy rate at 3 months, 12 months and at the end of the follow-up.ResultsA total of 65 patients were included: 35 in the cyclosporine group and 30 in the infliximab one. At 3 months the colectomy rate was 28.5% in the cyclosporine group and 17% in the infliximab group (p = 0.25), while 48% versus 17% at 12 months (p = 0.007, OR 4.7; 95% CI: 1.47-15.16). The 1-2-3 year cumulative colectomy rates were 48%, 54%, 57% in the cyclosporine group, and 17%, 23%, 27% in the infliximab group. At the end of the follow-up the colectomy rate was 60% versus 30% (p = 0.04, HR 2.2; 95% CI: 1.11-4.86). High level of C reactive protein (p = 0.04), extensive disease (p = 0.01) and no azathioprine treatment (p < 0.001) were related to the risk of colectomy.ConclusionThis study, despite being retrospective, indicates that both cyclosporine and infliximab are effective in avoiding a colectomy in steroid-refractory UC patients. During the follow-up the risk of a colectomy is higher in patients treated with cyclosporine than with infliximab.     

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: A single-center cohort study

Background & AimsThe combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use.MethodsIn a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥ 1 year and ≥ 2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments.ResultsIBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p = n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL,1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08–1.45; UC:HR 1.33;95%CI 1.15–1.55 for an increase by 5 years; p = 0.0023; p = 0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11–5.86,p = 0.0275), pancolitis in UC (HR 2.79;95%CI 1.05–7.40 p = 0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed).ConclusionsFistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.     

Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease

Background and aimsOver 10% of Crohn's disease (CD) patients annually lose response to infliximab. Infliximab trough levels (TL), concomitant immunosuppressants and endoscopic healing were proposed as predictors of favourable infliximab outcome. We assessed infliximab TL measured after induction therapy as predictors of sustained clinical response. Furthermore, we tried to identify other predictors of long-term benefit of infliximab therapy.MethodsWe included CD patients treated with infliximab between October 2007 and March 2010 who responded to 3-dose induction followed by maintenance therapy and in whom blood samples taken at treatment week 14 or 22 were available in blood bank. Sustained response to infliximab was defined as absence of treatment failure due to loss of response or drug intolerance.ResultsEighty four patients were included. Sustained response to infliximab was observed in 47 (56%) patients during a median follow-up of 25 months (14–37). Infliximab TL > 3 μg/ml were associated with a decreased risk of treatment failure (HR 0.34; 95% CI: 0.16–0.75), whereas the presence of antibodies against infliximab and need for corticosteroids increased this risk (HR 4.34; 95% CI: 1.51–12.5 and HR 2.49, 95% CI: 1.08–5.73, respectively). No impact of concomitant thiopurines was observed, although patients receiving thiopurines had higher infliximab TL than those without immunomodulators (5.51 vs. 0.71 μg/ml; p = 0.01).ConclusionDuring a median follow up of 2 years sustained response to infliximab was observed in slightly more than half of CD patients. Infliximab TL > 3 μg/ml at the start of maintenance regime were predicative of sustained response to infliximab.     

Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years

ObjectivesPerinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) have been proposed as markers for diagnosis and for subtyping of inflammatory bowel disease (IBD). The aim of this study was to investigate the association of p-ANCA and ASCA with a 10-year disease outcome in terms of cumulative rate of colectomy and relapse in a population-based European inception cohort of ulcerative colitis (UC) patients.MethodsSerum samples from 432 consenting patients were analysed for p-ANCA and ASCA. The results were compared with the cumulative colectomy rate, relapsing disease and total number of relapses. We used multiple regression analyses adjusted for age, sex, residence, disease extent at diagnosis, smoking, familial IBD and drug treatment to study the relationship between serological values and disease course.ResultsThe relapse rate was higher in the p-ANCA-positive patients: 82% (95% confidence interval [CI] 75–89%) compared with 67% (CI 62–72%, p = 0.011) in the p-ANCA-negative patients. The risk of relapsing disease course was higher by a factor of 1.4 (CI 1.1–1.8, p = 0.009) for p-ANCA-positive patients than for p-ANCA-negative patients, and the corresponding relative risk (RR) for the total number of relapses was 1.9 (CI 1.7–2.1, p < 0.001). In ASCA-positive patients RR for the total number of relapses was 1.8 (CI 1.5–2.1, p < 0.001). No significant association with colectomy rate was found for the presence of either p-ANCA or ASCA.ConclusionUC patients positive for p-ANCA and possibly for ASCA may have a more unfavourable long-term disease outcome in terms of relapse than UC patients without these markers.     

Long-term outcome after infliximab for refractory ulcerative colitis

Background and aimsInfliximab (IFX) has been shown efficacious for moderate-to-severe ulcerative colitis (UC), but data on long-term efficacy are lacking. We investigated long-term outcome including colectomy rates in outpatients treated with IFX for refractory UC in a single referral centre, and evaluated if predictors could be identified.MethodsThe first 121 outpatients (median age 38.0 years) with refractory UC treated with IFX were included. The primary outcome was colectomy-free survival. Secondary measures were sustained clinical response and serious adverse events.ResultsFrom the 81 patients (67%) with an initial clinical response to IFX, 68% had a sustained clinical response. No independent predictors of sustained clinical response could be identified. Over a median (IQR) follow-up period of 33.0 (17.0–49.8) months, 21 patients (17%) came to colectomy. Independent predictors of colectomy were absence of short-term clinical response [Hazard ratio 10.8 (95% CI 3.5–32.8), p < 0.001], a baseline CRP level ≥ 5 mg/L [Hazard ratio 14.5 (95% CI 2.0–108.6), p = 0.006] and previous IV treatment with corticosteroids and/or cyclosporine [Hazard ratio 2.4 (95% CI 1.1–5.9), p = 0.033]. Six patients developed a serious infection, three a malignancy, two a post-operative complication and one patient died (suicide).ConclusionsWith a median follow-up of 33.0 months after start of IFX, 17% of patients with refractory UC needed colectomy, while sustained clinical response was present in 68% of initial responders.     

Observational study on the efficacy of adalimumab for the treatment of ulcerative colitis and predictors of outcome

BackgroundInformation on efficacy and predictors of response to adalimumab in ulcerative colitis (UC) clinical practice is limited.AimAssessment of response to adalimumab and its predictors in an observational cohort study.MethodsRetrospective cohort study based on data obtained from ENEIDA registry. All patients diagnosed with UC treated with adalimumab were included. Response to adalimumab was evaluated at weeks 12, 28, and 54 according to the partial Mayo score, and requirement of colectomy until end of follow-up.Results48 patients with UC treated with adalimumab were included; 39 (81.3%) had previously received infliximab. Response rates at weeks 12, 28 and 54 were 70.8%, 43.2% and 35% respectively. Response to prior treatment with infliximab was the only predictive factor of response to adalimumab at week 12, which was obtained in 90% of infliximab remitters, 53.8% of responders and 33.3% of primary non-responders (p = 0.01).Colectomy was required in 11 patients (22.9%), after a mean time of 205 days. The only clinical independent predictor of colectomy was non-response to adalimumab at week 12: colectomy rates were 5/34 (14.7%) in responders and 6/14 (42.9%) in non-responders (p = 0.035), time free of colectomy was significantly reduced in non-responders (p = 0.01). Adalimumab withdrawal due to adverse events occurred in 4.2% of patients.ConclusionThis study shows that adalimumab is an effective treatment in patients with UC. If used as a second anti-TNF, previous achievement of remission with the first anti-TNF predicts response, and failure to achieve response at week 12 predicts colectomy.     

The impact of preoperative steroid use on short-term outcomes following surgery for inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) patients are frequently treated with steroids prior to surgery. We characterized the association between preoperative steroid use and postoperative complications in a large prospective cohort.MethodsWe identified patients who underwent major IBD-related abdominal surgery in the American College of Surgeon's National Surgical Quality Improvement Program (ACS-NSQIP) between 2005 and 2012. We compared the risk of postoperative complications and 30-day mortality between preoperative steroid users and non-users.ResultsWe identified 8260 Crohn's disease (CD) and 7235 ulcerative colitis (UC) patients who underwent major abdominal surgery. Preoperative steroid use was associated with higher risk of postoperative complications, excluding death, in both CD (22.6% vs. 18.5%, P < 0.0001) and UC (30.1% vs. 22.5%, P < 0.0001). The adjusted odds ratio for any postoperative complication associated with steroids was 1.26 (95% CI: 1.12–1.41) for CD and 1.44 (95% CI: 1.28–1.61) for UC. Infectious complications were more frequent with steroid use in both CD (15.2% vs. 12.9%, P = 0.004) and UC (19.4% vs. 15.6%, P < 0.0001), specifically intra-abdominal infections and sepsis. Steroid use was associated with increased risk of venous thromboembolism (VTE) in both CD (OR, 1.66; 95% CI: 1.17–2.35) and UC (OR, 2.66; 95% CI: 2.01–3.53). 30-day mortality did not differ among steroid users and non-users (6.8/1000 vs. 5.8/1000, P = 0.58 for CD; 13.5/1000 vs. 15.2/1000, P = 0.55 for UC).ConclusionsPreoperative steroids are associated with higher risk of postoperative sepsis and VTE in IBD. Increased infectious control measures and VTE prophylaxis may reduce adverse events.     

Incidence and natural history of ulcerative colitis in the Uppsala Region of Sweden 2005–2009 — Results from the IBD Cohort of the Uppsala Region (ICURE)

Background and aimsThe incidence of ulcerative colitis (UC) increased during the 20th century in Western Europe and the North America, but there are conflicting reports whether the incidence has declined, stabilized or continued to increase. The aim of this study was to evaluate the incidence of UC in the Uppsala Region, Sweden.MethodsAll new UC patients in Uppsala County (305,381 inhabitants) were prospectively registered during 2005–2006 and the same for all new UC patients in the Uppsala Region (642,117 inhabitants) during 2007–2009. The extent and severity of disease according to the Montreal classification, relapse rates and surgery were assessed.Results526 UC patients were included. The mean overall incidence for the time period was 20.0 (95% CI: 16.1–23.9) cases per 100,000 inhabitants. The incidence among children < 17 years of age was 8.9 per 100,000. The extent at diagnosis was evenly distributed (E1: n = 167, 32%, E2: n = 161, 31%, E3: n = 163, 31%). Half of the cases had moderate to severe symptoms (S1: n = 269, 51%, S2: n = 209, 40%, S3: n = 45, 8.6%). 228 (43%) relapsed and 13 (2.5%) required colectomy during the first year. Children had a higher proportion of extensive disease vs adults (27/42 vs 136/484), but no increased risk for severe symptoms or colectomy.ConclusionIn this prospective population-based study we found one of the highest incidences of UC in the world. The proportion of severe cases is comparable with historical data. The conclusion is that the nature of UC has not changed, only the incidence.     

Neoplasia in the ileoanal pouch following colectomy in patients with ulcerative colitis and primary sclerosing cholangitis

Background & AimsPrimary sclerosing cholangitis (PSC) is typically associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). PSC–IBD patients are at an increased risk for colorectal neoplasia. The ileal pouch-anal anastomosis (IPAA) is a treatment option for patients with medically refractory UC or neoplasia. However, little is known about the development of pouch neoplasia in PSC–UC patients following an IPAA. We aim to describe the incidence of pouch neoplasia in PSC–UC patients after an IPAA.MethodsWe conducted a retrospective chart review of patients with a confirmed diagnosis of PSC and IBD who underwent colectomy with IPAA followed by pouch surveillance between 1995 and 2012.ResultsSixty-five patients were included in the cohort and were followed up from the time of colectomy/IPAA for a median of 6 years. The most common indications for surgery were low-grade dysplasia (LGD) and refractory colitis. Only 3 patients developed evidence of neoplasia (LGD n = 1, high-grade dysplasia n = 1, adenocarcinoma n = 1). The cumulative 5-year incidence of pouch neoplasia was 5.6% (95% confidence intervals [CI], 1.8%–16.1%).ConclusionBased on our short-term follow-up, surveying the pouch frequently appears to be an unnecessary practice in PSC–IBD patients. Longer follow-up will be needed to develop an optimal surveillance strategy for the development of dysplasia and cancer in such patients.     

Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment

BackgroundControlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal.AimTo evaluate the need for high-dose budesonide (≥6 mg/d) to maintain clinical remission in CC.MethodsAnalysis of a multicentre retrospective cohort of 75 patients with CC (62.3 ± 1.5 years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9 mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6 mg/d) to maintain clinical remission.ResultsBudesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13–32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6–44) was associated with the need for high-dose budesonide in the multivariate analysis.Treatmentwith thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44–97%), allowing for withdrawal from or a dose decrease of budesonide.ConclusionsOne fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6 mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.     

Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance

BackgroundThe management of low-grade dysplasia (LGD) in ulcerative colitis (UC) patients remains unclear.AimThe aim of our study was to study the risk of progression of LGD to advanced neoplasia (AN), defined as high-grade dysplasia (HGD) or colorectal cancer (CRC) for UC patients undergoing surveillance based on location and morphology of LGD.Methods997 UC patients underwent 3152 surveillance colonoscopies from 1998 to 2011. Kaplan–Meier estimates and incidence rates calculated.ResultsOf the 102 patients with LGD (65 raised and 37 flat), 5 (4.9%) patients progressed to AN (3 HGD and 2 CRC) after a median follow-up of 36 months (interquartile range 18–71 months). Initial location of dysplasia was in the proximal colon in 47, distal colon in 55 patients. Four of the 5 (80%) patients with AN had initial dysplasia in the distal colon. Distal colonic LGD had an incidence rate for AN of 2.1 cases per 100 person years at risk, while proximal LGD had an incidence of 0.5 cases per 100 person years. Flat LGD in the distal colon was more likely to progress to AN [hazard ratio = 3.6; 95% confidence interval, CI (1.3–10.6)]. Twenty of the 102 patients (15 flat and 5 raised) underwent colectomy: 2 (10%) had evidence of AN in colectomy (1 HGD and 1 CRC), 9 had LGD and remaining 9 did not have dysplasia.ConclusionsThe frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN.     

Risk factors in German twins with inflammatory bowel disease: Results of a questionnaire-based survey

IntroductionEnvironmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews.MethodsRandomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n = 512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n = 392) and healthy subjects (n = 207).ResultsThe most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57–13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61–17.74, DZ CD OR, 7.66; 95% CI, 3.63–16.82, MZ UC OR, 3.82; 95% CI, 1.45–10.56, DZ UC OR, 3.08; CI, 1.63–5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15–38.12, DZ CD OR, 10.75; 95% CI, 4.82–25.55, MZ UC OR, 5.69; 95% CI, 1.89–19.48, DZ UC OR, 18.11; 95% CI, 7.34–50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33–77.14, DZ CD OR, 17.21; 95% CI, 4.47–112.5, MZ UC OR, 5.87; 95% CI, 1.61–28.0, DZ UC OR, 11.34; 95% CI, 4.81–29.67).ConclusionsThis study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease.     

Incidence of inflammatory bowel disease in the province of Styria,Austria, from 1997 to 2007: A population-based study

BackgroundThe incidence of inflammatory bowel disease (IBD) varies widely between different countries. This large variation is also observed for the incidence of its main two forms, ulcerative colitis (UC) and Crohn's disease (CD). Controversy exists whether IBD incidence is increasing, especially in western countries. Currently no data are available for Austria. This study therefore aimed to evaluate for the first time the incidence of IBD over an eleven-year period in Styria, a province of Austria with a population of 1.2 million.MethodsAll patients with an initial diagnosis of IBD between 1997 and 2007, who were Styrian residents, were eligible for this retrospective study. Data were acquired from electronically stored hospital discharge reports and individual reports by patients and physicians. According to population density Styria was divided into two rural and one urban area.ResultsThroughout the study period 1527 patients with an initial diagnosis of IBD were identified. The average annual incidence was 6.7 (95% CI 6.2–7.1) per 100,000 persons per year for CD and 4.8 (95% CI 4.5–5.2) for UC. The average annual incidence increased significantly (p < 0.01) for both diseases during the 11 year study period. Median age at initial diagnosis was 29 years (range 3–87) for CD and 39 years (range 3–94) for UC. At diagnosis, 8.5% of all IBD patients were < 18 years of age. The incidence of both CD and UC was significantly higher in the urban area than in rural areas (CD: 8.8, 95% CI 7.8–9.8 versus 5.5, 95% CI 4.7–6.4 and 5.9, 95% CI 5.3–6.7; [p < 0.001]; UC: 5.8, 95% CI 5.1–6.6 versus 4.0, 95% CI 3.4–4.7 and 4.7, 95% CI 4.1–5.4; [p = 0.04]).ConclusionWe observed an overall increase in the incidence of ulcerative colitis and Crohn's disease in a part of Austria during an eleven year period. IBD was more predominant in the largest urban area than in rural areas.     

Efficacy of tumour necrosis factor antagonists in stricturing Crohn’s disease: A tertiary center real-life experience

BackgroundStenosis is the most common complication of Crohn’s disease (CD). Long-term outcome of patients receiving tumour necrosis factor (TNF) antagonists for such disease complication is poorly understood.Methods51 CD patients (from July 2006 to November 2015) who had a diagnosis of small bowel or colonic stenosis, diagnosed by colonoscopy and/or MRI enterography, and were treated with TNF antagonists (adalimumab or infliximab) were enrolled.The primary outcome was to assess the rate of success of TNF antagonists on avoiding abdominal surgery for stricturing CD patients.Results20 patients (39.2%) underwent surgery during the follow-up period. The overall incidence of abdominal surgery was 1.8 per 100 person-months at risk, while the median time to surgery was 37.9 months. The univariable and multivariable Cox’s proportional hazards analysis of baseline parameters indicated that disease location (colonic vs ileal, HR: 28.2, 95% CI: 2.45–324, p = 0.007; ileocolonic vs ileal, HR: 3.38, 95% CI: 1.09–10.5, p = 0.035), prestenotic dilatation (per 1-mm increase, HR: 1.08, 95% CI: 1.01–1.15, p = 0.022) and the existence of non-perianal fistula (HR: 9.77, 95% CI: 2.99–31.9, p < 0.001) are independent risk factors for abdominal surgery.ConclusionsIn stricturing CD, anti-TNFs are effective in up to about two-thirds of the patients.     

Disease severity in familial cases of IBD

BackgroundPhenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence.AimTo know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases.Methods5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case.ResultsIn UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25–44] vs 37 years [IQR 27–49]; p < 0.0001); (CD: 27 years [IQR 21–35] vs 29 years [IQR 22–40]; p < 0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p = 0.04); (CD: 30.1% vs 23.6%; p < 0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p = 0.0001), penetrating behavior (21% vs 17.6%; p = 0.01) and perianal disease (32% vs 27.1%; p = 0.003). Differences are not influenced by degree of consanguinity.ConclusionWhen a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course.     

Oral tacrolimus as maintenance therapy for refractory ulcerative colitis—an analysis of outcomes in two London tertiary centres

BackgroundThe medical management of refractory ulcerative colitis (UC) remains a significant challenge. Two randomised controlled studies have demonstrated tacrolimus therapy is effective for the induction of remission of moderate to severe UC. However, the long term outcomes of UC patients treated with tacrolimus as maintenance therapy are not certain.AimsThis study aims to assess the efficacy of tacrolimus maintenance therapy for refractory UC.MethodsA retrospective review of patients with UC treated with tacrolimus at two London tertiary centres was performed. Clinical outcomes were assessed at six months, at the end of tacrolimus treatment, or at the last follow-up for patients continuing tacrolimus treatment. Modified Truelove–Witts score (mTW) and Mayo endoscopy subscores were calculated.Results25 patients with UC, treated with oral tacrolimus between 2005 and 2011, were identified. The median duration of tacrolimus treatment was 9 months (IQR 3.7–18.2 months). The median duration of follow-up was 27 months (range 3–66 months). At six months thirteen (52%) patients had achieved and maintained clinical response and eleven (44%) were in clinical remission. The mean mTW score decreased from 10 +/− 0.5 before therapy, to 5.8 +/− 0.8 (p ≤ 0.001 95% CI 2.7–5.8) at cessation of treatment or last follow-up. Mayo endoscopy subscore decreased from 2.6 +/− 0.1 to 1.2 +/− 0.2 (p ≤ 0.001 mean reduction 1.4, 95% CI 0.8–1.9). Eight patients (32%) subsequently underwent a colectomy within a mean time of 17 months (range 2–45 months).ConclusionTacrolimus is effective for the maintenance of refractory UC and can deliver sustained improvement in mucosal inflammation.     

Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis

BackgroundConflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease.AimsTo identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations.MethodsA systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models.ResultsOf the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I² = 69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I² = 38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26–3.39; I² = 78%); stroke (HR 1.59, 95% CI 1.29–1.96; I² = 45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I² = 68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I² = 0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population.ConclusionQTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.     

Real-World Incidence of Suboptimal Response to Anti-Tumor Necrosis Factor Therapy for Ulcerative Colitis: A Nationwide Population-Based Study

Background/AimsAlthough anti-tumor necrosis factor (TNF) agents have been widely used to treat ulcerative colitis (UC), the real-world incidence of suboptimal response to anti-TNF agents has not been thoroughly investigated, especially among Asians.MethodsUsing the Korean National Health Insurance database, we collected data on UC patients who initiated anti-TNF agents between July 1, 2014, and June 30, 2017. We assessed suboptimal responses, including anti-TNF discontinuation or dose escalation, switching to other biologics, augmentation with a non-biologic therapy, and the requirement for colectomy.ResultsA total of 1,268 patients were included as new anti-TNF users (infliximab 713, adalimumab 433, golimumab 122). The proportion of patients who experienced at least one suboptimal response within 1 year among all patients was 63.5%, including 59.1%, 69.5%, and 68.0% of patients treated with infliximab, adalimumab, and golimumab, respectively. The cumulative incidences of at least one suboptimal response over time were 41.5%, 63.7%, 80.5%, and 87.1% at 6, 12, 24, and 36 months, respectively. Cox proportional hazards modeling revealed that adalimumab was associated with a higher risk of at least one suboptimal response (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.13 to 1.48), dose escalation (HR, 4.35; 95% CI, 2.97 to 6.38) and discontinuation (HR, 1.25; 95% CI, 1.03 to 1.52) than infliximab. Golimumab was associated with a higher risk of switching to other biologics than infliximab (HR, 1.78; 95% CI, 1.21 to 2.60).ConclusionsMore than half of Korean UC patients had suboptimal responses to anti-TNF agents within 1 year. UC patients treated with infliximab might be less prone to suboptimal responses than those treated with adalimumab or golimumab.