IBD - Przegląd najnowszych doniesień literatury naukowej Grudzień 2010
Autor: Michał Springer
Źródło: MSD Polska
Am J Gastroenterol. 2010 Oct;105(10):2299-301.
Hepatosplenic T-cell lymphoma in inflammatory bowel disease: a possible thiopurine-induced chromosomal abnormality.
Kotlyar DS, Blonski W, Diamond RH, Wasik M, Lichtenstein GR.
Hepatosplenic T-cell lymphoma in inflammatory bowel disease: a possible thiopurine-induced chromosomal abnormality.
Kotlyar DS, Blonski W, Diamond RH, Wasik M, Lichtenstein GR.
Am J Gastroenterol. 2010 Oct;105(10):2299-301.
Hepatosplenic T-cell lymphoma in inflammatory bowel disease: a possible thiopurine-induced chromosomal abnormality.
Kotlyar DS, Blonski W, Diamond RH, Wasik M, Lichtenstein GR.
Clin Gastroenterol Hepatol. 2010 Dec;8(12):1099. Epub 2010 Aug 20.
Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease.
Fraser GM.
Inflamm Bowel Dis. 2010 Nov 28. [Epub ahead of print]
Development of the crohn's disease digestive damage score, the Lémann score.
Pariente B, Cosnes J, Danese S, Sandborn WJ, Lewin M, Fletcher JG, Chowers Y, D'Haens G, Feagan BG, Hibi T, Hommes DW, Irvine EJ, Kamm MA, Loftus EV Jr, Louis E, Michetti P, Munkholm P, Oresland T, Panés J, Peyrin-Biroulet L, Reinisch W, Sands BE, Schoelmerich J, Schreiber S, Tilg H, Travis S, van Assche G, Vecchi M, Mary JY, Colombel JF, Lémann M.
Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage.
Aliment Pharmacol Ther. 2011 Jan;33(1):5-22. doi: 10.1111/j.1365-2036.2010.04486.x. Epub 2010 Oct 29.
Review article: medical, surgical and radiological management of perianal Crohn's fistulas.
Tozer PJ, Burling D, Gupta A, Phillips RK, Hart AL.
Aliment Pharmacol Ther 2011; 33: 5-22 SUMMARY: Background Crohn's anal fistulas are common and cause considerable morbidity. Their management is often difficult; medical and surgical treatments rarely lead to true healing with frequent recurrence and complications. Aim To examine medical treatments previously and currently used, surgical techniques and the important role of optimal imaging. Methods We conducted a literature search in the Pub Med database using Crohn's, Anal Fistula, Surgery, Imaging and Medical Treatment as search terms. Results Antibiotics and immunosuppressants have a role, but slow initial response, side effects and relatively low remission rates of up to around a third with frequent recurrence limit their value. Long-term infliximab produces clinical remission in 36-58% of patients with combined medical and surgical management achieving optimal outcomes. Traditional and newer surgical procedures often have a high rate of recurrence with a significant risk of temporary or, in up to 10% of cases, permanent stomas, incontinence and unhealed or slowly healing wounds in 30%. Conclusions Management of Crohn's anal fistulas remains challenging. Established principles are to drain infection, use setons as required, aggressively manage active proctitis, give antibiotics, immunosuppressants and employ anti-TNFα therapy, and they demand significant co-operation between gastroenterologists and surgeons.
Aliment Pharmacol Ther. 2011 Jan;33(1):23-32. doi: 10.1111/j.1365-2036.2010.04489.x. Epub 2010 Oct 26.
Review article: explaining risks of inflammatory bowel disease therapy to patients.
Siegel CA.
Aliment Pharmacol Ther 2011; 33: 23-32 SUMMARY: Background Medical treatment for inflammatory bowel disease (IBD) has advanced significantly over the past decade, but it is important to communicate effectively the balance of benefits and risks of therapy to patients to facilitate informed medical decisions. Aim To review the available data describing the risk of side effects of IBD medications and to describe effective methods for communicating risk. Methods To identify relevant articles for this review, a PubMed search was conducted using relevant key words and phrases. In addition, reference lists from identified manuscripts were searched and recent abstracts from National meetings were reviewed. Results The steroid-sparing medications used for the treatment of IBD all carry risks of both common and rare adverse events. Trade-offs need to be made between the risks of these medications vs. the risks of poorly treated disease and corticosteroids. There has been significant research on how best to present risk data to patients, which is summarized in this review. Conclusions To ensure that our patients understand their choices and feel comfortable with their treatment, we need to communicate risk data to patients clearly. Patients comprehend absolute numbers better than relative risk, and when available, pictorial representations of data are preferred over solely presenting numerical outcomes.
J Gastrointest Surg. 2010 Dec;14(12):1859-65; discussion 1865-6. Epub 2010 Sep 25.
Perioperative anti-tumor necrosis factor therapy does not increase the rate of early postoperative complications in Crohn's disease.
Nasir BS, Dozois EJ, Cima RR, Pemberton JH, Wolff BG, Sandborn WJ, Loftus EV, Larson DW.
BACKGROUND: There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor (TNF) therapy and its relationship to postoperative outcome in Crohn disease. The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF therapy in the perioperative period.
METHODS: All patients undergoing surgery for Crohn disease from 2005 till 2008 were abstracted from a prospective database. Patients undergoing surgery which included a suture or staple line at risk for leaking were selected for the study. A retrospective review of medical records was performed. The study group comprised patients treated with perioperative anti TNF therapy (defined as treatment within 8 weeks preoperatively or up to 30 days postoperatively). The remainder of the patients did not receive perioperative anti TNF therapy. Patient characteristics, disease severity, medication use, operative intervention and 30-day complication were compared between the two groups.
RESULTS: Three hundred and seventy patients were selected for analysis in this study, of which 119 received perioperative anti TNF therapy and 251 did not. The groups were similar in baseline characteristics, perioperative risk factors and procedures. The group who received perioperative anti TNF therapy had a more severe disease overall as measured by the American College of Gastroenterology (ACG) categories of disease (50% severe fulminant disease in the perioperative anti-TNF therapy group versus 18% in the group that did not receive perioperative anti-TNF therapy, p < 0.001). There was no significant association of perioperative anti TNF therapy and any postoperative complications (27.9% in anti-TNF group versus 30.1% in no anti-TNF group, p = 0.63) nor intra-abdominal infectious complications (5.0% in anti-TNF group versus 7.2% in no anti-TNF group, p = 0.44). Univariate analysis showed that the only factors associated with an increase in postoperative intra-abdominal infections were age and penetrating disease.
CONCLUSIONS: The use of anti-TNF therapy in the perioperative period is safe and is not associated with an increase in overall or infectious complications in Crohn disease patients undergoing surgery.
Aliment Pharmacol Ther. 2010 Nov 17. doi: 10.1111/j.1365-2036.2010.04509.x. [Epub ahead of print]
Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study.
Schreiber S, Lawrance IC, Thomsen OO, Hanauer SB, Bloomfield R, Sandborn WJ.
Background Treatment options for fistulizing Crohn's disease (CD) are limited. Aim To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. Methods Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ≥100-point decrease from baseline in the Crohn's Disease Activity Index. Nonresponders (50/108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. Results The majority of patients (55/58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol-defined fistula closure (≥50% closure at two consecutive post-baseline visits ≥3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. Conclusion Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo.
Inflamm Bowel Dis. 2011 Jan;17(1):15-21. doi: 10.1002/ibd.21393.
Clinical variables as prognostic tools in pediatric-onset ulcerative colitis: A retrospective cohort study.
Moore JC, Thompson K, Lafleur B, Book LS, Jackson WD, O'Gorman MA, Black RE, Downey E Jr, Johnson DG, Matlak ME, Meyers RL, Scaife E, Guthery SL.
BACKGROUND: Clinical variables may identify a subset of patients with pediatric-onset ulcerative colitis (UC) (≤18 years at diagnosis) at risk for adverse outcomes. We postulated that routinely measured clinical variables measured at diagnosis would predict colectomy in patients with pediatric-onset UC.
METHODS: We conducted a chart review of patients with pediatric-onset UC at a single center over a 10-year period. We compared patients with and without colectomy across several variables, used proportional hazards regression to adjust for potential confounders, and assessed the ability of a UC risk score to predict colectomy.
RESULTS: Among 470 patients with inflammatory bowel disease ICD9-coded encounters, 155 patients had UC and 135 were eligible for analysis. The 1- and 3-year colectomy rates were 16.7% (95% confidence interval [CI]: 11.0%-24.8%) and 35.6% (26.7%-45.4%). White blood cell (WBC) count and hematocrit measured at diagnosis were associated with colectomy at 3 years, even after correcting for potential confounding variables. A UC Risk Score derived from the WBC count and hematocrit was strongly associated with colectomy risk, with a high negative predictive value (NPV) for colectomy at 1 and 3 years (NPV = 0.95 and 0.89, respectively), but low positive predictive value (PPV = 0.22 and 0.38, respectively).
CONCLUSIONS: A risk score calculated from WBC and hematocrit measured at diagnosis was associated with, but incompletely predictive of, colectomy in pediatric-onset UC. These data suggest 1) routinely measured clinical variables may have a prognostic role in risk stratification, and 2) multicenter prospective studies are needed to optimize risk stratification in pediatric UC. Our findings have impact on the design of such studies. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):22-29. doi: 10.1002/ibd.21418. Epub 2010 Aug 18.
Outcomes and adverse events in children and young adults undergoing tacrolimus therapy for steroid-refractory colitis.
Watson S, Pensabene L, Mitchell P, Bousvaros A.
BACKGROUND: Children with severe corticosteroid-resistant ulcerative colitis either need to undergo surgery or be treated with more intensive immunosuppression. Our aim was to characterize the short- and long-term outcomes and adverse events associated with the use of tacrolimus in a steroid-refractory pediatric population.
METHODS: We retrospectively reviewed the medical records of 46 children with steroid-refractory colitis treated with tacrolimus at Children's Hospital Boston between 1994 and 2008. Oral tacrolimus was initiated at a dose of 0.1 mg/kg twice a day and titrated to yield trough levels of 10-15 ng/mL for induction, and 5-10 ng/mL once in remission. The Pediatric Ulcerative Colitis Activity Index (PUCAI) and other measures of disease activity, adverse events, and long-term outcomes were assessed. Statistical analysis of outcomes was performed using SAS statistical software.
RESULTS: Ninety-three percent of patients were discharged without undergoing surgery. The median length of stay after starting tacrolimus was 10 days (range 4-37 days). The mean PUCAI score was 68 ± 13 prior to initiating tacrolimus, and 27 ± 18 at the time of hospital discharge. The probability of avoiding colectomy after starting tacrolimus was 40% at 26 months. The most common adverse events included hypertension (52%) and tremor (44%). There was one seizure and no deaths.
CONCLUSIONS: Tacrolimus is useful as induction therapy in pediatric patients with corticosteroid-refractory colitis and side effects are generally mild and reversible. Despite these findings, many patients develop exacerbations of colitis upon transition to maintenance therapies. The long-term colectomy rate in this challenging population remains ≈60% over time. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):30-38. doi: 10.1002/ibd.21386. Epub 2010 Sep 1.
Real-time tool to display the predicted disease course and treatment response for children with Crohn's disease.
Siegel CA, Siegel LS, Hyams JS, Kugathasan S, Markowitz J, Rosh JR, Leleiko N, Mack DR, Crandall W, Evans J, Keljo DJ, Otley AR, Oliva-Hemker M, Farrior S, Langton CR, Wrobel IT, Wahbeh G, Quiros JA, Silber G, Bahar RJ, Sands BE, Dubinsky MC.
BACKGROUND: Immunomodulators and biologics are effective treatments for children with Crohn's disease (CD). The challenge of communicating the anticipated disease course with and without therapy to patients and parents is a barrier to the timely use of these agents. The aim of this project was to develop a tool to graphically display the predicted risks of CD and expected benefits of therapy.
METHODS: Using prospectively collected data from 796 pediatric CD patients we developed a model using system dynamics analysis (SDA). The primary model outcome is the probability of developing a CD-related complication. Input variables include patient and disease characteristics, magnitude of serologic immune responses expressed as the quartile sum score (QSS), and exposure to medical treatments.
RESULTS: Multivariate Cox proportional analyses show variables contributing a significant increase in the hazard ratio (HR) for a disease complication include female gender, older age at diagnosis, small bowel or perianal disease, and a higher QSS. As QSS increases, the HR for early use of corticosteroids increases, in contrast to a decreasing HR with early use of immunomodulators, early or late biologics, and early combination therapy. The concordance index for the model is 0.81. Using SDA, results of the Cox analyses are transformed into a simple graph displaying a real-time individualized probability of disease complication and treatment response.
CONCLUSIONS: We have developed a tool to predict and communicate individualized risks of CD complications and how this is modified by treatment. Once validated, it can be used at the bedside to facilitate patient decision making. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):69-76. doi: 10.1002/ibd.21405.
Combined approach with infliximab, surgery, and methotrexate in severe fistulizing anoperineal Crohn's disease: Results from a prospective study.
Roumeguère P, Bouchard D, Pigot F, Castinel A, Juguet F, Gaye D, Capdepont M, Zerbib F, Laharie D.
BACKGROUND: Infliximab is the only medical therapy that has been proven to be effective in fistulizing Crohn's disease (CD), but the recurrence rate of fistulas is high despite maintenance therapy. The aim of this prospective study was to evaluate the short- and long-term efficacy of a combined schedule with infliximab, methotrexate, and sphincter-sparing surgery in patients with severe fistulizing anoperineal CD.
METHODS: From January 2006 to November 2007, all consecutive patients in three referral centers with severe fistulizing anoperineal CD were prospectively included after primary drainage. At inclusion, patients received three infliximab infusions at weeks 0, 2, and 6, and maintenance therapy with methotrexate. A second optimized surgical step consisting of at least removal of setons was performed between the second and the third infliximab infusions.
RESULTS: Thirty-four CD patients (26 women; median age 38.5 years) with complex anoperineal fistula were enrolled (including 9 with recto-vaginal fistulas, and 10 with anorectal stenosis). At week 14 the response rate was 85% with 74% complete responders. At 1 year, 50% were still responders; luminal CD worsening was the major cause of relapse. Median Perineal Disease Activity Index (PDAI) and magnetic resonance imaging (MRI) scores significantly decreased from baseline to week 50.
CONCLUSIONS: A combined approach with infliximab induction, two surgical sphincter-sparing steps and methotrexate is effective in achieving short-term response in severe fistulizing anoperineal CD. The best maintenance regimen remains to be determined. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):105-111. doi: 10.1002/ibd.21400.
Short CDAI: Development and validation of a shortened and simplified Crohn's disease activity index.
Thia K, Faubion WA Jr, Loftus EV Jr, Persson T, Persson A, Sandborn WJ.
BACKGROUND: The aim of this study was to develop a shortened Crohn's Disease Activity Index (CDAI).
METHODS: A short CDAI was developed retrospectively using patient-level data from four budesonide clinical trials to select variables from the full CDAI which best predicted health-related quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ), using the multiple linear regression model. The validity, reliability, and responsiveness of the short CDAI compared to the original CDAI were determined using data from nine clinical trials of budesonide.
RESULTS: The variables selected for the short CDAI were abdominal pain, diarrhea frequency, and general well-being. In all nine studies involving 1373 patients with active and inactive CD (5863 visits), the Pearson correlation coefficients between the short CDAI scores and the original CDAI scores at baseline (r = 0.899, P < 0.001), and the score differences (r = 0.963, P < 0.001) were excellent. The short CDAI accounted for 82.4% of the variance of the original CDAI. The intraclass correlation coefficient for the short CDAI was marginally better than that for the full CDAI, and both demonstrated good reliability (r = 0.600 versus r = 0.549). In patients with active CD who remitted during follow-up, the mean short CDAI scores decreased from 247 to 97, a score difference of 150 ± 60 points (P < 0.001). In patients with stable CD who relapsed, the mean short CDAI scores increased from 109 to 244 points, a score difference of 135 ± 62 points (P < 0.001).
CONCLUSIONS: The short CDAI is a valid, reliable, and responsive tool for the measurement of CD activity. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):423-439. doi: 10.1002/ibd.21349.
Epidemiology of pediatric inflammatory bowel disease: A systematic review of international trends.
Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM.
BACKGROUND: Temporal trends in the incidence of pediatric-onset inflammatory bowel disease (IBD) are controversial and a wide range of estimates have been reported worldwide. We conducted a systematic review of research describing the epidemiology of childhood-onset IBD to assess changes in incidence rates over time and to evaluate international differences.
METHODS: The following electronic databases were searched for articles published 1950-2009: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane IBD/Functional Bowel Disorders Group Specialised Trial Register. All included studies reported incidence or prevalence of IBD, Crohn's disease (CD) or ulcerative colitis (UC). Two authors independently completed the data extraction form for each eligible study. Choropleth maps demonstrated the international incidence of IBD, CD, and UC. Incidence of CD and UC was graphed using data from studies reporting rates in multiple time periods.
RESULTS: The search yielded 2209 references and review resulted in 139 included studies from 32 countries. A wide range of incidence was reported internationally; however, rates of IBD were not described in most countries. Twenty-eight studies (20.1%) used statistical analysis to assess trends over time, and 77.8% reported statistically significantly increased incidence of pediatric IBD. Of studies calculating statistical trends in CD incidence, 60% reported significantly increased incidence. Of similar UC studies, 20% reported significantly increased incidence.
CONCLUSIONS: Globally rising rates of pediatric IBD (due primarily to the rising incidence of CD) was demonstrated in both developed and developing nations; however, most countries lack accurate estimates. Analyzing incidence trends may help identify specific environmental and genetic risk factors for pediatric IBD. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):440-449. doi: 10.1002/ibd.21383.
Acute severe ulcerative colitis in children: A systematic review.
Turner D, Griffiths AM.
Pediatric ulcerative colitis (UC) has a more severe phenotype, reflected by more extensive disease and a higher rate of acute severe exacerbations. The pooled steroid-failure rate among 291 children from five studies is 34% (95% confidence interval [CI]: 27%-41%). It is suggested that corticosteroids should be dosed between 1-1.5 mg/kg up to 40-60 mg daily. Food restriction has a limited role in severe UC and should be generally discouraged in children who do not have a surgical abdomen. Appraisal of radiologic findings in children must recognize the variation in colonic width with age and size. Data suggest that the Pediatric UC Activity Index (PUCAI), determined at day 3, should be used to screen for patients likely to fail corticosteroids (>45 points), and at day 5 to dictate the introduction of second-line therapy (>65-70 points). Cyclosporine is successful in children with severe colitis but its use should be restricted to 3-4 months while bridging to thiopurine treatment (pooled short-term success rate 81% [95% CI: 76%-86%]; n = 94 from eight studies). Infliximab may be as effective as cyclosporine (75% pooled short-term response (95% CI: 67%-83%); n = 126, six studies) with a pooled 1-year response of 64% (95% CI: 56%-72%). In toxic megacolon, in patients refractory to one salvage medical therapy, and in chronic severe disease, colectomy may be preferred. Decision-making regarding colectomy in children must consider the toxicity of medication consumed over many future years, the quality of life and self-image associated with either choice, as well as both functional outcomes and, in females, fertility following pouch procedures. (Inflamm Bowel Dis 2011;).
Hepatosplenic T-cell lymphoma in inflammatory bowel disease: a possible thiopurine-induced chromosomal abnormality.
Kotlyar DS, Blonski W, Diamond RH, Wasik M, Lichtenstein GR.
Clin Gastroenterol Hepatol. 2010 Dec;8(12):1099. Epub 2010 Aug 20.
Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease.
Fraser GM.
Inflamm Bowel Dis. 2010 Nov 28. [Epub ahead of print]
Development of the crohn's disease digestive damage score, the Lémann score.
Pariente B, Cosnes J, Danese S, Sandborn WJ, Lewin M, Fletcher JG, Chowers Y, D'Haens G, Feagan BG, Hibi T, Hommes DW, Irvine EJ, Kamm MA, Loftus EV Jr, Louis E, Michetti P, Munkholm P, Oresland T, Panés J, Peyrin-Biroulet L, Reinisch W, Sands BE, Schoelmerich J, Schreiber S, Tilg H, Travis S, van Assche G, Vecchi M, Mary JY, Colombel JF, Lémann M.
Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage.
Aliment Pharmacol Ther. 2011 Jan;33(1):5-22. doi: 10.1111/j.1365-2036.2010.04486.x. Epub 2010 Oct 29.
Review article: medical, surgical and radiological management of perianal Crohn's fistulas.
Tozer PJ, Burling D, Gupta A, Phillips RK, Hart AL.
Aliment Pharmacol Ther 2011; 33: 5-22 SUMMARY: Background Crohn's anal fistulas are common and cause considerable morbidity. Their management is often difficult; medical and surgical treatments rarely lead to true healing with frequent recurrence and complications. Aim To examine medical treatments previously and currently used, surgical techniques and the important role of optimal imaging. Methods We conducted a literature search in the Pub Med database using Crohn's, Anal Fistula, Surgery, Imaging and Medical Treatment as search terms. Results Antibiotics and immunosuppressants have a role, but slow initial response, side effects and relatively low remission rates of up to around a third with frequent recurrence limit their value. Long-term infliximab produces clinical remission in 36-58% of patients with combined medical and surgical management achieving optimal outcomes. Traditional and newer surgical procedures often have a high rate of recurrence with a significant risk of temporary or, in up to 10% of cases, permanent stomas, incontinence and unhealed or slowly healing wounds in 30%. Conclusions Management of Crohn's anal fistulas remains challenging. Established principles are to drain infection, use setons as required, aggressively manage active proctitis, give antibiotics, immunosuppressants and employ anti-TNFα therapy, and they demand significant co-operation between gastroenterologists and surgeons.
Aliment Pharmacol Ther. 2011 Jan;33(1):23-32. doi: 10.1111/j.1365-2036.2010.04489.x. Epub 2010 Oct 26.
Review article: explaining risks of inflammatory bowel disease therapy to patients.
Siegel CA.
Aliment Pharmacol Ther 2011; 33: 23-32 SUMMARY: Background Medical treatment for inflammatory bowel disease (IBD) has advanced significantly over the past decade, but it is important to communicate effectively the balance of benefits and risks of therapy to patients to facilitate informed medical decisions. Aim To review the available data describing the risk of side effects of IBD medications and to describe effective methods for communicating risk. Methods To identify relevant articles for this review, a PubMed search was conducted using relevant key words and phrases. In addition, reference lists from identified manuscripts were searched and recent abstracts from National meetings were reviewed. Results The steroid-sparing medications used for the treatment of IBD all carry risks of both common and rare adverse events. Trade-offs need to be made between the risks of these medications vs. the risks of poorly treated disease and corticosteroids. There has been significant research on how best to present risk data to patients, which is summarized in this review. Conclusions To ensure that our patients understand their choices and feel comfortable with their treatment, we need to communicate risk data to patients clearly. Patients comprehend absolute numbers better than relative risk, and when available, pictorial representations of data are preferred over solely presenting numerical outcomes.
J Gastrointest Surg. 2010 Dec;14(12):1859-65; discussion 1865-6. Epub 2010 Sep 25.
Perioperative anti-tumor necrosis factor therapy does not increase the rate of early postoperative complications in Crohn's disease.
Nasir BS, Dozois EJ, Cima RR, Pemberton JH, Wolff BG, Sandborn WJ, Loftus EV, Larson DW.
BACKGROUND: There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor (TNF) therapy and its relationship to postoperative outcome in Crohn disease. The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF therapy in the perioperative period.
METHODS: All patients undergoing surgery for Crohn disease from 2005 till 2008 were abstracted from a prospective database. Patients undergoing surgery which included a suture or staple line at risk for leaking were selected for the study. A retrospective review of medical records was performed. The study group comprised patients treated with perioperative anti TNF therapy (defined as treatment within 8 weeks preoperatively or up to 30 days postoperatively). The remainder of the patients did not receive perioperative anti TNF therapy. Patient characteristics, disease severity, medication use, operative intervention and 30-day complication were compared between the two groups.
RESULTS: Three hundred and seventy patients were selected for analysis in this study, of which 119 received perioperative anti TNF therapy and 251 did not. The groups were similar in baseline characteristics, perioperative risk factors and procedures. The group who received perioperative anti TNF therapy had a more severe disease overall as measured by the American College of Gastroenterology (ACG) categories of disease (50% severe fulminant disease in the perioperative anti-TNF therapy group versus 18% in the group that did not receive perioperative anti-TNF therapy, p < 0.001). There was no significant association of perioperative anti TNF therapy and any postoperative complications (27.9% in anti-TNF group versus 30.1% in no anti-TNF group, p = 0.63) nor intra-abdominal infectious complications (5.0% in anti-TNF group versus 7.2% in no anti-TNF group, p = 0.44). Univariate analysis showed that the only factors associated with an increase in postoperative intra-abdominal infections were age and penetrating disease.
CONCLUSIONS: The use of anti-TNF therapy in the perioperative period is safe and is not associated with an increase in overall or infectious complications in Crohn disease patients undergoing surgery.
Aliment Pharmacol Ther. 2010 Nov 17. doi: 10.1111/j.1365-2036.2010.04509.x. [Epub ahead of print]
Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study.
Schreiber S, Lawrance IC, Thomsen OO, Hanauer SB, Bloomfield R, Sandborn WJ.
Background Treatment options for fistulizing Crohn's disease (CD) are limited. Aim To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. Methods Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ≥100-point decrease from baseline in the Crohn's Disease Activity Index. Nonresponders (50/108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. Results The majority of patients (55/58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol-defined fistula closure (≥50% closure at two consecutive post-baseline visits ≥3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. Conclusion Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo.
Inflamm Bowel Dis. 2011 Jan;17(1):15-21. doi: 10.1002/ibd.21393.
Clinical variables as prognostic tools in pediatric-onset ulcerative colitis: A retrospective cohort study.
Moore JC, Thompson K, Lafleur B, Book LS, Jackson WD, O'Gorman MA, Black RE, Downey E Jr, Johnson DG, Matlak ME, Meyers RL, Scaife E, Guthery SL.
BACKGROUND: Clinical variables may identify a subset of patients with pediatric-onset ulcerative colitis (UC) (≤18 years at diagnosis) at risk for adverse outcomes. We postulated that routinely measured clinical variables measured at diagnosis would predict colectomy in patients with pediatric-onset UC.
METHODS: We conducted a chart review of patients with pediatric-onset UC at a single center over a 10-year period. We compared patients with and without colectomy across several variables, used proportional hazards regression to adjust for potential confounders, and assessed the ability of a UC risk score to predict colectomy.
RESULTS: Among 470 patients with inflammatory bowel disease ICD9-coded encounters, 155 patients had UC and 135 were eligible for analysis. The 1- and 3-year colectomy rates were 16.7% (95% confidence interval [CI]: 11.0%-24.8%) and 35.6% (26.7%-45.4%). White blood cell (WBC) count and hematocrit measured at diagnosis were associated with colectomy at 3 years, even after correcting for potential confounding variables. A UC Risk Score derived from the WBC count and hematocrit was strongly associated with colectomy risk, with a high negative predictive value (NPV) for colectomy at 1 and 3 years (NPV = 0.95 and 0.89, respectively), but low positive predictive value (PPV = 0.22 and 0.38, respectively).
CONCLUSIONS: A risk score calculated from WBC and hematocrit measured at diagnosis was associated with, but incompletely predictive of, colectomy in pediatric-onset UC. These data suggest 1) routinely measured clinical variables may have a prognostic role in risk stratification, and 2) multicenter prospective studies are needed to optimize risk stratification in pediatric UC. Our findings have impact on the design of such studies. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):22-29. doi: 10.1002/ibd.21418. Epub 2010 Aug 18.
Outcomes and adverse events in children and young adults undergoing tacrolimus therapy for steroid-refractory colitis.
Watson S, Pensabene L, Mitchell P, Bousvaros A.
BACKGROUND: Children with severe corticosteroid-resistant ulcerative colitis either need to undergo surgery or be treated with more intensive immunosuppression. Our aim was to characterize the short- and long-term outcomes and adverse events associated with the use of tacrolimus in a steroid-refractory pediatric population.
METHODS: We retrospectively reviewed the medical records of 46 children with steroid-refractory colitis treated with tacrolimus at Children's Hospital Boston between 1994 and 2008. Oral tacrolimus was initiated at a dose of 0.1 mg/kg twice a day and titrated to yield trough levels of 10-15 ng/mL for induction, and 5-10 ng/mL once in remission. The Pediatric Ulcerative Colitis Activity Index (PUCAI) and other measures of disease activity, adverse events, and long-term outcomes were assessed. Statistical analysis of outcomes was performed using SAS statistical software.
RESULTS: Ninety-three percent of patients were discharged without undergoing surgery. The median length of stay after starting tacrolimus was 10 days (range 4-37 days). The mean PUCAI score was 68 ± 13 prior to initiating tacrolimus, and 27 ± 18 at the time of hospital discharge. The probability of avoiding colectomy after starting tacrolimus was 40% at 26 months. The most common adverse events included hypertension (52%) and tremor (44%). There was one seizure and no deaths.
CONCLUSIONS: Tacrolimus is useful as induction therapy in pediatric patients with corticosteroid-refractory colitis and side effects are generally mild and reversible. Despite these findings, many patients develop exacerbations of colitis upon transition to maintenance therapies. The long-term colectomy rate in this challenging population remains ≈60% over time. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):30-38. doi: 10.1002/ibd.21386. Epub 2010 Sep 1.
Real-time tool to display the predicted disease course and treatment response for children with Crohn's disease.
Siegel CA, Siegel LS, Hyams JS, Kugathasan S, Markowitz J, Rosh JR, Leleiko N, Mack DR, Crandall W, Evans J, Keljo DJ, Otley AR, Oliva-Hemker M, Farrior S, Langton CR, Wrobel IT, Wahbeh G, Quiros JA, Silber G, Bahar RJ, Sands BE, Dubinsky MC.
BACKGROUND: Immunomodulators and biologics are effective treatments for children with Crohn's disease (CD). The challenge of communicating the anticipated disease course with and without therapy to patients and parents is a barrier to the timely use of these agents. The aim of this project was to develop a tool to graphically display the predicted risks of CD and expected benefits of therapy.
METHODS: Using prospectively collected data from 796 pediatric CD patients we developed a model using system dynamics analysis (SDA). The primary model outcome is the probability of developing a CD-related complication. Input variables include patient and disease characteristics, magnitude of serologic immune responses expressed as the quartile sum score (QSS), and exposure to medical treatments.
RESULTS: Multivariate Cox proportional analyses show variables contributing a significant increase in the hazard ratio (HR) for a disease complication include female gender, older age at diagnosis, small bowel or perianal disease, and a higher QSS. As QSS increases, the HR for early use of corticosteroids increases, in contrast to a decreasing HR with early use of immunomodulators, early or late biologics, and early combination therapy. The concordance index for the model is 0.81. Using SDA, results of the Cox analyses are transformed into a simple graph displaying a real-time individualized probability of disease complication and treatment response.
CONCLUSIONS: We have developed a tool to predict and communicate individualized risks of CD complications and how this is modified by treatment. Once validated, it can be used at the bedside to facilitate patient decision making. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):69-76. doi: 10.1002/ibd.21405.
Combined approach with infliximab, surgery, and methotrexate in severe fistulizing anoperineal Crohn's disease: Results from a prospective study.
Roumeguère P, Bouchard D, Pigot F, Castinel A, Juguet F, Gaye D, Capdepont M, Zerbib F, Laharie D.
BACKGROUND: Infliximab is the only medical therapy that has been proven to be effective in fistulizing Crohn's disease (CD), but the recurrence rate of fistulas is high despite maintenance therapy. The aim of this prospective study was to evaluate the short- and long-term efficacy of a combined schedule with infliximab, methotrexate, and sphincter-sparing surgery in patients with severe fistulizing anoperineal CD.
METHODS: From January 2006 to November 2007, all consecutive patients in three referral centers with severe fistulizing anoperineal CD were prospectively included after primary drainage. At inclusion, patients received three infliximab infusions at weeks 0, 2, and 6, and maintenance therapy with methotrexate. A second optimized surgical step consisting of at least removal of setons was performed between the second and the third infliximab infusions.
RESULTS: Thirty-four CD patients (26 women; median age 38.5 years) with complex anoperineal fistula were enrolled (including 9 with recto-vaginal fistulas, and 10 with anorectal stenosis). At week 14 the response rate was 85% with 74% complete responders. At 1 year, 50% were still responders; luminal CD worsening was the major cause of relapse. Median Perineal Disease Activity Index (PDAI) and magnetic resonance imaging (MRI) scores significantly decreased from baseline to week 50.
CONCLUSIONS: A combined approach with infliximab induction, two surgical sphincter-sparing steps and methotrexate is effective in achieving short-term response in severe fistulizing anoperineal CD. The best maintenance regimen remains to be determined. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):105-111. doi: 10.1002/ibd.21400.
Short CDAI: Development and validation of a shortened and simplified Crohn's disease activity index.
Thia K, Faubion WA Jr, Loftus EV Jr, Persson T, Persson A, Sandborn WJ.
BACKGROUND: The aim of this study was to develop a shortened Crohn's Disease Activity Index (CDAI).
METHODS: A short CDAI was developed retrospectively using patient-level data from four budesonide clinical trials to select variables from the full CDAI which best predicted health-related quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ), using the multiple linear regression model. The validity, reliability, and responsiveness of the short CDAI compared to the original CDAI were determined using data from nine clinical trials of budesonide.
RESULTS: The variables selected for the short CDAI were abdominal pain, diarrhea frequency, and general well-being. In all nine studies involving 1373 patients with active and inactive CD (5863 visits), the Pearson correlation coefficients between the short CDAI scores and the original CDAI scores at baseline (r = 0.899, P < 0.001), and the score differences (r = 0.963, P < 0.001) were excellent. The short CDAI accounted for 82.4% of the variance of the original CDAI. The intraclass correlation coefficient for the short CDAI was marginally better than that for the full CDAI, and both demonstrated good reliability (r = 0.600 versus r = 0.549). In patients with active CD who remitted during follow-up, the mean short CDAI scores decreased from 247 to 97, a score difference of 150 ± 60 points (P < 0.001). In patients with stable CD who relapsed, the mean short CDAI scores increased from 109 to 244 points, a score difference of 135 ± 62 points (P < 0.001).
CONCLUSIONS: The short CDAI is a valid, reliable, and responsive tool for the measurement of CD activity. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):423-439. doi: 10.1002/ibd.21349.
Epidemiology of pediatric inflammatory bowel disease: A systematic review of international trends.
Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM.
BACKGROUND: Temporal trends in the incidence of pediatric-onset inflammatory bowel disease (IBD) are controversial and a wide range of estimates have been reported worldwide. We conducted a systematic review of research describing the epidemiology of childhood-onset IBD to assess changes in incidence rates over time and to evaluate international differences.
METHODS: The following electronic databases were searched for articles published 1950-2009: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane IBD/Functional Bowel Disorders Group Specialised Trial Register. All included studies reported incidence or prevalence of IBD, Crohn's disease (CD) or ulcerative colitis (UC). Two authors independently completed the data extraction form for each eligible study. Choropleth maps demonstrated the international incidence of IBD, CD, and UC. Incidence of CD and UC was graphed using data from studies reporting rates in multiple time periods.
RESULTS: The search yielded 2209 references and review resulted in 139 included studies from 32 countries. A wide range of incidence was reported internationally; however, rates of IBD were not described in most countries. Twenty-eight studies (20.1%) used statistical analysis to assess trends over time, and 77.8% reported statistically significantly increased incidence of pediatric IBD. Of studies calculating statistical trends in CD incidence, 60% reported significantly increased incidence. Of similar UC studies, 20% reported significantly increased incidence.
CONCLUSIONS: Globally rising rates of pediatric IBD (due primarily to the rising incidence of CD) was demonstrated in both developed and developing nations; however, most countries lack accurate estimates. Analyzing incidence trends may help identify specific environmental and genetic risk factors for pediatric IBD. (Inflamm Bowel Dis 2011;).
Inflamm Bowel Dis. 2011 Jan;17(1):440-449. doi: 10.1002/ibd.21383.
Acute severe ulcerative colitis in children: A systematic review.
Turner D, Griffiths AM.
Pediatric ulcerative colitis (UC) has a more severe phenotype, reflected by more extensive disease and a higher rate of acute severe exacerbations. The pooled steroid-failure rate among 291 children from five studies is 34% (95% confidence interval [CI]: 27%-41%). It is suggested that corticosteroids should be dosed between 1-1.5 mg/kg up to 40-60 mg daily. Food restriction has a limited role in severe UC and should be generally discouraged in children who do not have a surgical abdomen. Appraisal of radiologic findings in children must recognize the variation in colonic width with age and size. Data suggest that the Pediatric UC Activity Index (PUCAI), determined at day 3, should be used to screen for patients likely to fail corticosteroids (>45 points), and at day 5 to dictate the introduction of second-line therapy (>65-70 points). Cyclosporine is successful in children with severe colitis but its use should be restricted to 3-4 months while bridging to thiopurine treatment (pooled short-term success rate 81% [95% CI: 76%-86%]; n = 94 from eight studies). Infliximab may be as effective as cyclosporine (75% pooled short-term response (95% CI: 67%-83%); n = 126, six studies) with a pooled 1-year response of 64% (95% CI: 56%-72%). In toxic megacolon, in patients refractory to one salvage medical therapy, and in chronic severe disease, colectomy may be preferred. Decision-making regarding colectomy in children must consider the toxicity of medication consumed over many future years, the quality of life and self-image associated with either choice, as well as both functional outcomes and, in females, fertility following pouch procedures. (Inflamm Bowel Dis 2011;).
Przegląd Gastroenterologiczny
