Clin Gastroenterol Hepatol. 2016 Feb 2.
The Crohn's disease-ulcerative colitis clinical appraisal.
D'Haens G, Bressler B, Danese S, et al.

No abstract available


Crohns Colitis. 2016 Jan 22.
Use of anti-TNFα agents and time to first-time surgery in paediatric patients with ulcerative colitis and Crohn's disease.
Larsen MD, Qvist N, Nielsen J, et al.

BACKGROUND AND AIMS: It is debated whether the need for surgery has changed following introduction of anti-TNFα agents in the treatment of paediatric ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to describe the implementation of anti-TNFα agents in paediatric patients, and the need of first-time surgery before and after introduction of anti-TNFα agents.
METHODS: In the Danish National Patient Registry, we identified incident paediatric patients diagnosed from 1998. We calculated the proportion of patients receiving anti-TNFα agents within 5 years from diagnosis, and the cumulative 5 year proportion of surgery, according to calendar periods of diagnosis.
RESULTS: At the end of our study period [2007 and 2008], 29-41% of CD children were treated with anti-TNFα agents within 5 years, and for UC children 17-19%. In 1278 CD patients, the 5 year cumulative proportions of surgery were 14.6-15.6% for children diagnosed in 1998-2008 and 9.7% (95% confidence interval [CI]: 6.7-13.7) for those diagnosed in 2009-2013. In 1468 UC patients, the cumulative proportion of surgery suggested a decline in patients diagnosed after mid 2005, and the hazard ratio of surgery was 0.64 [95% CI: 0.47-0.86] after the introduction of anti-TNFα agents compared with before. For UC patients diagnosed in 2009-2013, the 5 year cumulative proportion of surgery was 7.6% [95% CI: 5.2-11.2].
CONCLUSIONS: This nationwide study showed an extensive use of anti-TNFα agents at the end of our study period. For UC children, our data suggest a decline in the proportion of surgery in the period of increasing use of anti-TNFα agents.


J Crohns Colitis. 2016 Jan 22. [Epub ahead of print]
Anti-TNF monotherapy for Crohn's disease: a 13-year multicentre experience.
Peyrin-Biroulet L, Salleron J, Filippi J, et al.


BACKGROUND: Anti-tumour necrosis factor [TNF] therapy in combination with thiopurine is the most effective strategy for Crohn's disease, but raises safety concerns.
METHODS: In a retrospective multicentre study, we investigated long-term outcome of patients starting anti-TNF monotherapy for Crohn's disease and investigated whether introducing an immunomodulator in patients losing response to anti-TNF monotherapy is effective for resetting immunogenicity.
RESULTS: A total of 350 adult patients with Crohn's disease received either infliximab [n = 178, 51%] or adalimumab [n = 172, 49%] monotherapy. Mean duration of follow-up was 42 months. An immunomodulator was initiated in 53 patients [15%]. At last follow-up, 73.1% [n = 38] were in clinical remission [one patient with missing data]. Multivariate analysis identified anti-TNF type [higher need for starting immunomodulator for infliximab than for adalimumab; p = 0.0058] and first- vs second-/third-/fourth-line anti-TNF therapy [p = 0.014] as predictors of immunomodulator initiation. Among the 18 patients with available data, introduction of an immunomodulator was able to restore infliximab trough level within the therapeutic range and to induce clinical remission in 10 patients [55%]. Cumulative probability of remaining on anti-TNF therapy was 57.9% at 5 years among the 297 patients not starting an immunomodulator during follow-up.
CONCLUSION: An immunomodulator was initiated in 15% of patients with Crohn's disease starting anti-TNF monotherapy. Independent predictors of immunomodulator initiation were infliximab use and second-/third-/fourth-line anti-TNF therapy. Resetting immunogenicity with an immunomodulator was effective in half of patients in a sub-study. Persistence of anti-TNF treatment at 5 years was observed in half of the 297 patients not starting an immumodulator in a real-life setting.


Inflamm Bowel Dis. 2016 Jan 27.
Anti-TNF therapy within 2 years of Crohn's disease diagnosis improves patient outcomes: a retrospective cohort study.
Ma C, Beilman CL, Huang VW, et al.


BACKGROUND: Although biological agents targeting tumor necrosis factor (TNF) alpha are effective in the management of Crohn's disease (CD), use of anti-TNF agents is often delayed until after failure of other treatment modalities, resulting in potentially long delays between diagnosis and initiation of infliximab or adalimumab. We aim to determine if early treatment with anti-TNF agents reduces the rate of surgical resection and clinical secondary loss of response in CD patients.
METHODS: A retrospective cohort study was conducted evaluating CD outpatients who were primary responders to anti-TNF therapy, on a maintenance regimen with infliximab or adalimumab from 2003 to 2014. Patients were stratified by time to first dose of anti-TNF therapy; early initiation was defined as starting anti-TNF therapy within 2 years of diagnosis. The primary outcome was occurrence of surgical resection or clinical secondary loss of response requiring dose escalation. Kaplan-Meier analysis was used to assess time to the primary outcomes.
RESULTS: One hundred ninety CD patients met inclusion criteria (100 infliximab, 90 adalimumab). Median follow-up duration was 154.4 weeks (inter quartile range, 106.4-227.8). Fifty-three patients (27.9%) had early initiation of anti-TNF therapy. Fewer patients in the early initiation group required surgery (5.7% versus 30.7%, P < 0.001) or experienced clinical secondary loss of response (45.3% versus 67.2%, P = 0.006). In Kaplan-Meier analysis, early initiation of anti-TNF therapy prolonged time to surgery (P = 0.001) and secondary loss of response (P = 0.006).
CONCLUSIONS: In CD patients, early initiation of infliximab or adalimumab within the first 2 years of diagnosis reduces the rate of surgery and secondary loss of response requiring dose escalation


J Crohns Colitis. 2016 Jan 28.
Identifying patients at high risk of loss of response to infliximab maintenance therapy in paediatric Crohn's disease.
Dupont-Lucas C, Sternszus R, Ezri J, et al.


BACKGROUND AND AIMS: Loss of response (LOR) to infliximab (IFX) resulting in discontinuation of therapy is a frequent problem encountered in paediatric Crohn's disease. Although identifying patients at risk of failure could have important implications for follow-up, literature in this area remains sparse. Our primary aim was to identify predictors of LOR to IFX among patients who were responders to induction. Secondary aim was to identify predictors of non-response to induction.
METHODS: A retrospective cohort of patients with paediatric Crohn's disease treated with IFX between 2000 and 2013 was followed until LOR to IFX or transfer to adult care. Predictors of response to induction therapy were studied by multivariate logistic regression. Time to treatment failure was analysed by multivariate Cox model.
RESULTS: Two-hundred-and-forty-eight patients were eligible for the study. Of these, 196 (79%) were responders to induction (57% clinical remission and 22% clinical response) and 52 (21%) were non-responders. Steroid resistance was the only variable independently associated with primary non-response (OR 4.57 (95% CI 1.67 - 12.50), p=0.002). Thirty-one of the 196 responders discontinued IFX due to LOR after a mean 1.6 ± 1.3 years of treatment. Predictors of LOR were: level of response to induction (clinical response vs. clinical remission: HR 3.74 (95% CI 1.80 - 7.80), p=0.0004 and isolated colonic disease: HR 2.72 (95% CI 1.30 - 5.71), p=0.008.
CONCLUSIONS: Patients who fail to achieve clinical remission after induction and/or who have isolated colonic disease are at increased risk of LOR to IFX.


Inflamm Bowel Dis. 2016 Jan 27.
Comparison of fecal inflammatory markers in Crohn's disease.
Wright EK, Kamm MA, De Cruz P, et al.


BACKGROUND: Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection.
METHODS: Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed.
RESULTS: FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 μg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 μg/g) and were higher in recurrent disease than remission (275 versus 72 μg/g, P < 0.001; 5.7 versus 1.6 μg/g, P = 0.007; 2.0 versus 0.8 μg/g, P = 0.188). FC > 135 μg/g, FL > 3.4 μg/g, and FS > 10.5 μg/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not.
CONCLUSIONS: FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.


Am J Gastroenterol. 2016 Feb 9.
Systematic review and meta-analysis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids.
Narula N, Marshall JK, Colombel JF, et al.


OBJECTIVES: Acute severe steroid-refractory ulcerative colitis (UC) carries a poor prognosis and requires optimal management. A systematic review and meta-analysis were conducted to assess cyclosporine and infliximab (IFX) as rescue agents in patients with steroid-refractory UC.
METHODS: A literature search identified studies that investigated IFX and cyclosporine in steroid-refractory UC patients. The primary outcome was short-term response to treatment. Secondary outcomes included the rates of colectomy at 3 months and 12 months, adverse drug reactions, post-operative complications in those who received rescue therapy but underwent colectomy subsequently, and mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported.
RESULTS: Overall, 16 studies with 1,473 participants were eligible for inclusion. Among three randomized controlled trials, no significant difference was seen with IFX compared with cyclosporine with regard to treatment response and 3- or 12-month colectomy. Among 13 non-randomized studies, IFX was associated with significantly higher rates of treatment response (OR 2.96 (95% CI 2.12-4.14, χ2=6.50, I2=0%)) and a lower 12-month colectomy rate (OR 0.42 (95% CI 0.22-0.83, χ2=30.94, I2=71%)), with no significant difference seen in the 3-month colectomy rate (OR 0.53 (95% CI 0.22-1.28, χ2=22.73, I2=69%)) compared with cyclosporine. There were no significant differences between IFX and cyclosporine in adverse drug-related events, post-operative complications, or mortality.
CONCLUSIONS: In the management of steroid-refractory severe UC, no definitive difference between IFX and cyclosporine is demonstrated by randomized trials, but non-randomized studies suggest that IFX is associated with better treatment response and lower risk of colectomy at 12 months. Prospective studies comparing dose-optimized IFX with cyclosporine are needed.


J Crohns Colitis. 2016 Jan 27.
Similar short- and long-term colectomy rates with ciclosporin and infliximab treatment in hospitalised ulcerative colitis patients.
Duijvis N, Ten Hove A, Ponsioen C, et al.


BACKGROUND AND AIMS: Ciclosporin A (CsA) and infliximab (IFX) are similarly effective in preventing short-term colectomy in ulcerative colitis (UC) patients, but long-term data are scarce. We aimed to compare short- and long-term efficacy of CsA and IFX by analysing colectomy rates and failure of remission-induction treatment as outcome parameters for treatment success.
METHODS: We retrospectively studied hospitalised UC patients who received CsA or IFX for moderate-to-severe UC, between January 2000 and April 2014. The primary end point was time to colectomy, and treatment failure (defined as colectomy or another remission-induction treatment with corticosteroids, CsA or IFX) was used as secondary end point. Variables possibly affecting colectomy outcomes were analysed.
RESULTS: Fifty-five patients were studied for colectomy outcome and 58 patients for treatment failure. A significantly longer follow-up duration was available for CsA-treated patients (P<0.001, both subcohorts). Patients showed comparable patient- and disease-specific characteristics. Colectomy rates did not differ significantly at 3, 12 and 36 months: 36% versus 29%, 58% versus 48%, and 64% versus 67% for CsA- and IFX-treated patients, respectively. Multivariate Cox regression analysis revealed the lowest hazard ratio for colectomy in patients concomitantly using thiopurines (HR 0.28 (CI 0.13-0.64), P=0.002). Treatment failure rates were not significantly different at 3, 12 and 36 months: 35% versus 48%, 51% versus 68%, and 62% versus 83% for CsA- and IFX-treated patients, respectively.
CONCLUSION: Treatment with CsA and IFX is similarly effective in preventing short- and long-term colectomy in hospitalised UC patients. Furthermore, failure rates of these remission-induction treatments were comparable.


Eur J Gastroenterol Hepatol. 2016 Jan 29.
Colectomy rates in patients with ulcerative colitis following treatment with infliximab or ciclosporin: a systematic literature review.
Thorne K, Alrubaiy L, Akbari A, et al.


This review aimed to compile all available published data on colectomy rates following treatment using infliximab or ciclosporin in adult ulcerative colitis patients and to analyse colectomy rates, timing to colectomy and postcolectomy mortality for each treatment. We systematically reviewed the literature after 1990 reporting colectomy rates in ulcerative colitis patients treated with infliximab or ciclosporin, excluding articles on paediatric patients, patients with indeterminate colitis or Crohn's disease and bowel surgery not related to ulcerative colitis. We presented weighted mean colectomy rates and mortality rates. Cox's regression was used to assess time to colectomy adjusting for colitis severity, patient age and sex. We tabulated 78 studies reporting on ciclosporin and/or infliximab and colectomy rates or postcolectomy mortality rates. Not all studies reported data in a standardized manner. Infliximab had a significantly lower colectomy rate than ciclosporin at 36 months when analysing all studies, studies directly comparing infliximab and ciclosporin and studies using severe colitis patients, but not at 3, 12 or 24 months. Severity and age were key indicators in the likelihood of undergoing colectomy after treatment. Postcolectomy mortality rates were less than 1.5% for both drugs. This review indicates that long-term colectomy rates following infliximab are significantly lower than ciclosporin in the longer term, and that postcolectomy mortality following infliximab and ciclosporin is very low. However, many key data items were missing from research articles, reducing our ability to establish with more confidence the actual impact of these two drugs on colectomy rates and postcolectomy mortality rates.


Scand J Gastroenterol. 2016 Jun;51(6):700-5.
Comparison of the therapeutic efficacy and safety between tacrolimus and infliximab for moderate-to-severe ulcerative colitis: a single center experience.
Nuki Y, Esaki M, Asano K, et al.


OBJECTIVE: Both tacrolimus (Tac) and infliximab (IFX) are effective for moderate-to-severe ulcerative colitis (UC). The aim of this study was to compare the therapeutic efficacy and safety of both drugs.
MATERIALS AND METHODS: We performed a retrospective analysis of 46 patients with moderate-to-severe UC who were treated either by Tac (n = 21) or IFX (n = 25). We compared the remission and response rates for 10 weeks between the two groups. In patients who achieved a clinical response, the subsequent relapse rate was compared. The overall adverse events were also compared between the two groups.
RESULTS: The remission and response rates at week 10 did not differ between patients treated with Tac (67% and 86%, respectively) and patients treated with IFX (76% and 92%, respectively). Among 41 patients showing a clinical response, eight of 23 patients treated with IFX and eight of 18 patients treated with Tac showed a subsequent relapse. The risk of relapse was not different between the two groups. While no serious adverse events were observed, the incidence of adverse events was higher in patients treated with Tac than in those treated with IFX.
CONCLUSION: Tac and IFX may be equally efficacious for the induction and maintenance of remission in patients with UC while minor adverse events are more frequent with the former treatment


Clin Gastroenterol Hepatol. 2016 Jan 29.
Mucosal healing is associated with improved long-term outcomes of patients with ulcerative colitis: a systematic review and meta-analysis.
Shah SC, Colombel JF, Sands BE, et al.


BACKGROUND & AIMS: The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH compared to those without MH.
METHODS: We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared to those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids, and rate of MH, after at least 52 weeks.
RESULTS: We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds-ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval [CI], 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared to patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy.
CONCLUSIONS: In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy.


Crohns Colitis. 2016 Jan 22.
Consecutive measurements by fecal immunochemical test in quiescent ulcerative colitis patients can detect clinical relapse.
Hiraoka S, Kato J, Nakarai A, et al.


BACKGROUND: We have reported that results of the quantitative fecal immunochemical test (FIT), hemoglobin concentrations in feces measured by using an antibody for human hemoglobin, effectively reflect the mucosal status of ulcerative colitis (UC). The aim of this study was to evaluate the predictability of flare-up in quiescent UC patients by consecutive FIT evaluation.
METHODS: UC patients who fulfilled the following criteria by the index colonoscopy were enrolled: clinical remission, mucosal healing (Mayo endoscopic subscore; 0), and negative FIT (less than 100 ng/mL). These patients were followed-up prospectively every 1-3 months by monitoring patient symptoms and FIT results between index and subsequent colonoscopies.
RESULTS: The periods between two colonoscopies (median 2.51 years) of 83 patients (49 males, median age at onset 34 years, median disease duration 9.74 years) were analyzed. None of the 43 (52%) patients who maintained negative FIT throughout the observation period exhibited clinical relapse. On the other hand, 25/40 (63%) patients who showed positive conversion of FIT during the period experienced relapse. The cutoff FIT value of 450 ng/mL could predict relapse with 73% positive predictive value, and 96% negative predictive value. Moreover, positive conversion of FIT preceded occurrence of symptoms by one month or more in nearly one third of patients with relapse.
CONCLUSIONS: Consecutive measurements of FIT in quiescent UC patients who achieved mucosal healing with negative FIT would help identify patients with clinical relapse whose symptoms had not presented yet. Further investigations are required for more precise prediction of relapse with this modality.


Crohns Colitis. 2016 Jan 22.
Tuberculosis in anti-tumor necrosis factor treated inflammatory bowel disease patients after the implementation of preventive measures: compliance with recommendations and safety of retreatment.
Carpio D, Jauregui-Amezaga A, de Francisco R, et al.


INTRODUCTION: Despite having adopted preventive measures, tuberculosis (TB) in anti-tumor necrosis factor (anti-TNF) treated inflammatory bowel disease (IBD) patients may still occur. Data about the causes and characteristics of TB cases in this scenario are lacking.
AIMS & METHODS: Our aim is to describe the characteristics of TB in anti-TNF treated IBD patients after the publication of the Spanish prevention guidelines and to evaluate the safety of restarting anti-TNF after a TB diagnosis. In this multicenter retrospective descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary.
RESULTS: We collected 50 TB cases in anti-TNF treated IBD patients, 60% male, median age 37.3 years (IQR 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated TB and 26% extra-pulmonary TB. In 30 patients (60%), TB cases developed despite following the recommended preventive measures; not performing PPD or booster was the main failure in compliance with recommendations. In 17 patients (34%), anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation.
CONCLUSION: In anti-TNF treated IBD patients, tuberculosis may still occur despite following recommended preventive measures, though a significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe.


Dig Surg. 2016 Feb 10;33(3):182-189.
Prolonged medical therapy increases the risk of surgical complications in patients with severe ulcerative colitis.
Kimura H, Kunisaki R, Tatsumi K, et al.


AIMS: To determine the risk factors of surgical complications and the optimal timing of surgery for patients with severe ulcerative colitis (UC). METHODS: One hundred one UC patients who had undergone surgery for a severe indication were retrospectively reviewed. Indications included severe disease unresponsive to medical therapy, massive bleeding, toxic megacolon, and colon perforation. Outcomes were compared based on the occurrence or absence of surgical complications. Patients with severe disease unresponsive to medical therapy were investigated separately to determine the optimal timing of surgery. RESULTS: There was no significant difference regarding the use of rescue therapy. The duration of all medical therapy for a severe attack was the only significant factor associated with a surgical complication (p = 0.032). In patients with severe disease unresponsive to medical therapy, the receiver operating characteristic curve analysis showed that 30.5 days was the length of medical therapy after which the risk of surgical complications significantly increased. CONCLUSIONS: In patients with severe UC, rescue therapy itself was not related to an increased risk of surgical complications. However, prolonged medical therapy increased the risk of surgical complications. Patients should undergo surgery within 30 days from the institution of medical therapy for a severe attack.


Curr Treat Options Gastroenterol. 2016 Feb 11.
Treat to target in inflammatory bowel disease.
Bossuyt P, Vermeire S.


OPINION STATEMENT: With the expanding armamentarium in IBD the current treatment targets can be reached. By optimally using our drugs we can avoid long-term complications in IBD. For this the therapeutic strategy has to be changed from a clinically driven approach to a target-driven strategy. Currently mucosal healing, normalization of biomarkers, histological healing, and healing on abdominal imaging are proposed targets. Correct phenotyping of the patient before initiation of therapy is mandatory. Once treatment is initiated a continuous re-evaluation with consequent adaptation of the treatment when goals are not (yet) reached is needed. Both escalation and de-escalation should be considered. Drug levels can be used as a guidance to reach these targets.


J Crohns Colitis. 2016 Feb 19.
Mechanism of action of anti-TNF therapy in inflammatory bowel disease.
Levin AD, Wildenberg ME, van den Brink GR.


Several anti-TNF blocking strategies have been evaluated in patients with Crohn's disease. Compounds that have been tested included the full monoclonal IgG1 antibodies infliximab and adalimumab, the pegylated anti-TNF F(ab')2 fragment certolizumab, an IgG4 anti-TNF CDP571 with reduced affinity for the Fc receptor, the soluble TNF receptor I onercept and the TNF receptor II-Fc fusion protein etanercept. The endpoints of these studies suggest that not all methods of blocking TNF are equal. Here we will review the differences in the clinical, biochemical and endoscopic endpoints of the major clinical studies. Collectively the data suggest that only IgG1 monoclonal antibodies have the ability to induce complete clinical, biochemical and endoscopic remission. We discuss the potential multiple modes of action that may contribute to the response to full IgG1 anti-TNFs focusing on the rapid induction of lamina propria T cell apoptosis and Fc receptor dependent induction of M2 type wound healing macrophages. We discuss how novel insights into the mechanism of action of anti-TNFs in Crohn's disease may contribute to the development of novel anti-TNFs with improved efficacy.


Aliment Pharmacol Ther. 2016 Feb 19.
Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.
Kennedy NA, Warner B, Johnston EL, et al.


BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis.
METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years="" white="" cell="" count="" hr="" 3="" 22="" for="">5.25 × 109 /L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU.
CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.


Gastroenterol. 2016 Feb 20.
Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease.
Ikhtaire S, Shajib MS, Reinisch W, et al.


Gastrointestinal symptoms such as abdominal pain, dyspepsia, and diarrhea are relatively nonspecific and a common cause for seeking medical attention. To date, it is challenging for physicians to differentiate between functional and organic gastrointestinal conditions and it involves the use of serological and endoscopic techniques. Therefore, a simple, noninvasive, inexpensive, and effective test would be of utmost importance in clinical practice. Fecal calprotectin (FC) is considered to be a reliable biomarker that fulfills these criteria. FC can detect intestinal inflammation, and its level correlates well with macroscopic and histological inflammation as detected by colonoscopy and biopsies, respectively. FC has a decent diagnostic accuracy for differentiating organic diseases and functional disorders because of its excellent negative predictive value in ruling out inflammatory bowel disease (IBD) in symptomatic undiagnosed patients. There is accumulating evidence that FC has been effectively used to monitor the natural course of IBD, to predict relapse, and to see the response to treatment. This novel biomarker has the ability to assess mucosal healing (MH), which is a therapeutic goal in IBD management. A literature search was carried out using PubMed with the keywords FC, IBD, intestinal inflammation, and MH. In our review, we provide an overview of the utility and scope of FC as a biomarker in patients with IBD as well as undiagnosed patients with lower gastrointestinal symptoms.


Scand J Gastroenterol. 2016 Feb 19:1-6.
Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission.
Kim JH, Cheon JH, Park Y, et al.


OBJECTIVE: The aim of this study was to identify the effect of mucosal healing (MH) on clinical relapse in patients with ulcerative colitis (UC) who are in clinical remission, with special reference to Mayo endoscopic subscore 0.
METHODS: Between November 2005 and December 2013, medical records from a total of 215 patients with UC who underwent colonoscopic examination at the time of clinical remission were retrospectively reviewed. Endoscopic MH was defined as a '0 point' of Mayo endoscopic subscore (Mayo 0). Patients were categorized into two groups according to Mayo endoscopic subscore and then analyzed.
RESULTS: The baseline characteristics of both groups (MH vs. no-MH), including age at diagnosis, gender, and initial clinical and colonoscopic findings, were not significantly different. The median follow-up duration was 80 (12-118) months. Factors predictive of longer clinical remission duration were age .30 years at diagnosis (.30 years vs. < 30 years; hazard ratio [HR] 3.16, 95% CI 1.88-5.30, p < 0.001), shorter interval between diagnosis and clinical remission (< 15 months vs. .15 months; HR 1.93, 95% CI 1.13-3.28, p = 0.015), and presence of MH at clinical remission (HR 1.95, 95% CI 1.15-3.32, p = 0.014). With a Cox regression model, patients with MH at clinical remission were more likely to have longer duration of clinical remission than patients without MH.
CONCLUSION: The achievement of MH, Mayo 0 in particular, in patients with UC who are in clinical remission is important in predicting a favorable disease course prognosis.


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