Category Archives: inflammatory bowel disease

Prospective Monitoring of Calprotectin for Crohn’s Disease

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A recent study (full text link: Wright EK, et al. Gastroenterol May 2015 Volume 148, Issue 5, Pages 938–947) shows that stool calprotectin levels can be useful to monitor Crohn’s disease (Links from AGA twitter feed).  This study measured levels as part of The Post-Operative Crohn’s Endoscopic Recurrence (POCER) study.

Here’s the abstract, followed by some comments:

Background & Aims

Crohn’s disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa.

Methods

We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn’s disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn’s disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients.

Results

Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months.

Conclusions

In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.

Some key points from the discussion:

  • “The POCER study recently showed that postoperative endoscopic monitoring, together with treatment intensification for early recurrence, is superior to standard drug therapy alone in preventing disease recurrence, at least in the short term. However, such endoscopic monitoring is invasive, expensive, cannot be repeated frequently, and, in some patients, will yield a normal result.” [De Cruz, P., Kamm, M.A., Hamilton, A.L. et al. Crohn’s disease management after intestinal resection: a randomised trial. Lancet. 2014; (Epub ahead of print)]
  • The POCER study had all postoperative patients receive 3 months of metronidazole.  High-risk patients also received thiopurine or adalimumab (if thiopurine intolerant) therapy.  High-risk was defined as patients who were smokers, patients with perforating disease, or patients with 1 or more previous resections.
  • “In our study we have shown that FC concentration is increased markedly before surgery and decreases substantially after resection of all macroscopic disease at 6 months”
  • “The present study has shown that FC concentration is sufficiently sensitive to monitor for recurrence of Crohn’s disease, and has a high enough negative predictive value to be confident that few patients with recurrence will be missed.” The authors, though, recommend serial measurement rather than relying on a single assay.
  • Calprotectin: “At each time point in our study, a cut-off value of 100 μg/g had an NPV of 90% or greater, with the best combination of sensitivity and specificity.”
  • An important limitation of these findings is that patients had to have all macroscopic disease removed at the time of surgery.  Thus, these findings are not generalizable to patients with residual upper gastrointestinal disease.
  • “These results confirm the accuracy, utility and superiority of fecal calprotectin compared with CRP or CDAI as a monitoring tool and screening test for endoscopic recurrence of Crohn’s disease in the postoperative population.”

Additional summary of this information on AGA Journals blog:  Measurement of Fecal Calprotectin.  An excerpt:

In an editorial that accompanies the article, Alain M. Schoepfer and James D. Lewis explain that the role of fecal calprotectin in assessing post-operative recurrence has been debated because of inconsistent results in mainly small studies. The strengths of the study of Wright et al include its large size, prospective design, endoscopic validation, and longitudinal inter-individual measurements of fecal calprotectin.

Tests for biomarkers such as fecal calprotectin can be repeated more frequently than colonoscopies. This advantage could overcome the lower levels of sensitivity with which single measurements of biomarkers detect recurrence. Schoepfer and Lewis say that studies are needed to determine the optimal frequency for measuring fecal calprotectin.

However, they conclude that measurement of fecal calprotectin could have an important role in monitoring Crohn’s disease recurrence after intestinal resection; it is clearly superior to measurement of c-reactive protein or CDAI score.

Proposed algorithm for using calprotectin: In the editorial, they propose that patients with low or medium risk of “permanent bowel dysfunction as a consequence of post-operative recurrence” could use fecal calprotectin measurements every 3-6 months.  They propose a cut-off of 50 mcg/g in those with medium risk and a cut-off of 100 mcg/g in those with low risk.  Those who exceeded cut-off would need colonoscopy.  Among high risk patients, they recommend proceeding directly to colonoscopy every 6-12 months to assess for recurrence.  All patients who had recurrence of disease greater than i1 would need treatment for recurrence. (Related gutsandgrowth blog: Only One Chance to Make a First Impression).

This year’s 22Q at the zoo was on May 17th, 2015:

22Q at the Zoo. More than 100 zoos across the world participate to improve awareness of 22Q deletion syndrome

22Q at the Zoo. More than 100 zoos across the world participate to improve awareness of 22Q deletion syndrome.  With Karlene Coleman, Nancy Morris, and Jennifer Hochman.

Why ImproveCareNow is Needed

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A few recent articles make a strong argument for collaborative networks, like ImproveCareNow, to improve data collection to determine the most effective therapies.

  1. Kierkus J, et al. JPGN 2015; 60: 580-85.
  2. Audu GK, et al. JPGN 2015; 60: 586-91
  3. Dotson JL, et al. Inflamm Bowel Dis 2015; 21: 1109-14
  4. Saps M, et al. JPGN 2015; 60: 645-53.

A brief description of each study.

1. This study presented a multi-center randomized open-label trial of 99 pediatric patients with Crohn’s disease (CD) who were administered infliximab (IFX) along with an immunomodulator (azathioprine or methotrexate).  After a 10 week induction, 84 were randomized to either monotherapy for 54 weeks or dual therapy for 26 weeks. The authors did not find significant differences in response between the groups.  However, they reached a conclusion: “Twenty-six weeks likely represent (sic) the safe duration of combined IFX/immunomodulator therapy in our sample of pediatric patients with CD.”

2. The second study described three cases of chronic recurrent multifocal ostesomyelitis (CRMO) associated with inflammatory bowel disease.  They tried to identify all pediatric cases in UK in the last 10 years. (As an aside, I have treated one teenager with CRMO and ulcerative colitis.)

3. The third study is a retrospective single center of 30 patients with pediatric Crohn’s disease (CD) who developed intra-abdominal abscesses (IAA) over a 12-year period.  The authors note that this is “the largest single-center review of children and adolescents with CD and IAA to date.” Yet due to the small sample size, the study provides little guidance on this important medical problem; there were no predictors of successful medical or percutaneous drainage therapy.  In addition, with the increasing use of biologics, the authors note that “the issue of which patients will eventually require surgery is even less clear.” Changes in imaging (eg. MRE) and changes in medical management (eg. more enteral nutrition and less corticosteroids) are not discussed.

4. The fourth study is a comprehensive review of randomized placebo-controlled pharmacological clinical trials in children with functional abdominal pain disorders.  They found “no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP-FGIDs in children were found. Most studies were single center based and had a small sample size.  The methods and outcomes were heterogeneous…We found a considerable risk of bias in most studies…There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures.”

Each of these studies makes a compelling argument for collaborative research networks.  The first study had a relatively small number of patients, short follow-up period, lack of blinding, and numerous methodological limitations.  How did the authors determine that 26 weeks was the time to stop dual therapy? Among adults with CD, a well-designed SONIC study (NEJM 2010; 362: 1383) showed the superiority of dual therapy during the study period.  In children, because of concerns about thiopurine safety, the best approach is still unclear. The second study identified only three patients despite examining a large population.  Similarly, the third study describes 30 patients with a common complication of CD but provides little insight.

The fourth study is a cautionary tale illustrating the lack of progress due to the absence of collaborative research.  Reports indicate a high prevalence of functional abdominal pain; one study indicated that abdominal pain affects “38% of school children weekly” (J Pediatr 2009; 154: 322-6).  In fact, studies on the high prevalence of this disorder dates back for 60 years (Apley, 1975; Apley & Hale, 1973; Apley & Naish, 1958). Despite the prevalence of this problem, the data for all of the treatments is poor.  The lack of progress in defining treatments for functional abdominal pain is multifactorial, including the following:

  • Cost: For many of the available treatments, there is not a financial incentive to conduct research.
  • Biomarker: lack of objective markers for improvement
  • Disease Stigma: many people attribute functional disorders as being due solely to psychological factors
  • Physician Champions: in pediatric gastroenterology, it took concerted physician efforts over many years to develop ImproveCareNow.  Similar physician champions would be needed to improve the outcomes for children with functional disorders

Bottomline: While ImproveCareNow has a lot of work ahead including improving data reliability and ascertaining accurate outcome measures, I think the effort is forward-thinking and will make a difference in understanding and treating children with IBD.  ImproveCareNow has more than 600 participating pediatric gastroenterologists and more than 20,000 patients. What I would like to see is a sister network to address the morbidity from functional disorders so that in 60 years (or sooner), we will be better equipped to treat children with abdominal pain that is not due to IBD.

Related blog posts:

Fox Theater

Fox Theater

Brains and Bowels: Kids with IBD Do Fine in School

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A recent study (Singh H, et al. J Pediatr 2015; 166: 1128-33) showed that overall academic performance was not affected for children with inflammatory bowel disease (IBD).

Study characteristics:

University of Manitoba Database IBD population (n=337) was matched by age, sex, and area of residence to 10 randomly selected controls (n=3093).

Key findings:

  • There were no significant differences in the 2 groups in standardized scores or enrollment in grade 12
  • Lower socioeconomic status and diagnosis with a mental health problem (6-month before or after IBD diagnosis) were independent predictors of worse outcomes

Akin to the quote above, I’ve often felt that it is difficult to think clearly when having severe bowel dysfunction.  At the same time, some of our patients accomplish so much despite their physical setbacks.

Bottomline: This study provides reassurance that children with IBD should be able to complete their course work.

Chicago

Chicago

 

Tackling Crohn’s Perianal Fistulizing Disease

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I am fortunate to work closely with several well-qualified pediatric surgeons and colorectal surgeons.  When faced with perianal fistulas, I have discussions with them to help optimize therapy.  Understanding exactly what and why the surgeons do what they do has not always been clear to me.  Four recent articles provide guidelines for the management of Crohn’s perianal disease.  The color figures in the articles make understanding what is done pretty obvious.

  • Schwartz DA et al. Inflamm Bowel Dis 2015; 21: 723-30. Overview.
  • Ong EMW et al. Inflamm Bowel Dis 2015; 21: 731-36. Focus on imaging.
  • Schwartz DA et al. Inflamm Bowel Dis 2015; 21: 737-52. Critical evaluation of Medications
  • Fichera A, Zoccali M. Inflamm Bowel Dis 2015; 21: 753-58. Critical evaluation of Surgical Approaches

The first guideline provides a summary statement combining aspects of both medical and surgical management.  Basic anatomy and classification are reviewed (a color figure similar to reproduction below helps describe the types of fistula).

Simple vs Complex fistula is reviewed.  A “Simple fistula is a superficial, intersphincteric or low transspincteric fistula that has only 1 opening and is not associated with an abscess and/or does not connect to an adjacent structure such as the vagina or bladder.”  All others are complex fistulas.  The MRI classifcation is also reviewed (Figure 5).

Other points:

  • For fistulizing disease, top-down cotherapy (anti-TNF/immunomodulator) therapy is recommended.  Antibiotics are recommended in the short term.
  • Placement of a draining seton (for complex fistulas) helps to maintain fistula drainage until the track becomes inactive on medical treatment.
  • A treatment algorithm (Figure 7) notes that endoscopy, imaging (EUS or MRI) and exam under anesthesia are key first steps.  Decision tree then divides based on whether there is rectal inflammation, and whether fistula is simple or complex.
  • Surgical options include fistulotomy, fibrin glue, fistula plug, seton placement, advancement flaps and proctectomy.

Bottomline: These set of articles should serve as a useful reference when managing perianal disease.

Related blog posts:

 

 

 

Headlines and Shorts for IBD and IBS

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“Higher Levels of Knowledge Reduce Health Care Costs in Patients with Inflammatory Bowel Disease.” Inflamm Bowel Dis 2015; 21: 615-22.  This retrospective observational cohort study asked 91 patients to complete a questionnaire about their knowledge on the disease after 1 year of follow-up. The authors noted an association between higher levels of knowledge and lower health care costs. While their are many limitations to this study, it is hard to argue with the conclusion that better education is worthwhile; it may also improve outcome and costs.

“Surgery and Postoperative Recurrence in Children with Crohn Disease.” Hansen LF et al. JPGN 2015; 60: 347-51. In a retrospective study dating back to 1978, the authors noted a high recurrence of surgery in children (n=115) with Crohn disease (CD).  More than 1 bowel resection was needed in 39%. The use of biologics occurred late in the study and its potential effect on lowering recurrent resection is unclear in this study. Related post:  More Lessons in TNF Therapy (Part 1) | gutsandgrowth

“Risk of Drug-Induced Liver Injury from Tumor Necrosis Factor Antagonists.” Bjornsson ES, et al. Clin Gastroenterol Hepatol 2015; 13: 602-08.  9 cases of DILI associated with infliximab (1 in 120 patients), 1 case (of 270) with adalimumab, and 1 case (of 430) associated with etanercept. 8 of 11 patients who were tested for ANA were positive. DILI was treated with steroids in 5 patients. 8 patients went on to receive a different anti-TNF without recurrent liver dysfunction. Related blog posts:

“The Prevalence of Intestinal Parasites is Not Greater Among Individuals with Irritable Bowel Syndrome: A Population-based Case-control Study” Clin Gastroenterol Hepatol 2015; 13: 507-13. Related post: Does it make sense to look for parasites in RAP …

More on Adalimumab (Humira) in Pediatrics

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A recent ‘observational cohort’ study (Cozijnsen M, et al. JPGN 2015; 60: 205-10) provides more information regarding the use of adalimumab in pediatrics.  The authors attempted to identify all Dutch patients <18 years of age with Crohn’s disease who received adalimumab after infliximab therapy.  Excluded patients were those with “bad treatment adherence,” conflicting comorbidity, and previous participation in prospective study by Hyams et al Gastroenterol 2012; 143: 365-74 (Related blog post: Adalimumab for children with Crohn’s disease | gutsandgrowth).

Key findings:

  • 53 patients met the inclusion criteria.  12 received monotherapy with adalimumab; cotherapy in 21 with thiopurines, 11 with methotrexate, 7 with steroids, and 2 with enteral nutrition.
  • Median followup was only 12 months.
  • Remission noted in 34 (64%) patients based on either wPCDAI or PGA (physician global assessment) after a median of 3.3 months.  Remission was durable in 50% of these patients for 2 years.
  • Adalimumab failure was noted in 18 (34%).  Only 3 patients in this study were primary infliximab nonresponders and only 1/3 responded to adalimumab.
  • One serious adverse event (infection) was reported.

One weakness of this study (& many others) is its reliance on clinical disease activity indices rather than more precise measures of mucosal healing.

Take-home point: This small study provides some information about the utility of adalimumab in clinical practice in pediatrics.  As noted in other studies, those with a loss of response to infliximab, rather than primary nonresponders, appear to have a more favorable response to adalimumab. In addition, the glaring weakness in this study (i.e. small number of participants) validates the rationale behind efforts like ImproveCareNow which can generate information quickly from a large patient population.

Related study: “Levels of Drug and Antidrug Antibodies are Associated with Outcome of Interventions After Loss of Response to Infliximab or Adalimumab.” Yanai H, et al. Clin Gastroenterol Hepatol 2015; 13: 522-30. Retrospective study of 247 adult and pediatric patients. Key findings:

  • Patients with adequate trough levels (>4.5 mcg/mL for adalimumab, >3.8 mcg/mL for infliximab) “identified patients who failed to respond to an increase in dosage or a switch to another anti-TNF agent with 90% specificity.”
  • “Levels of antibody against adalimumab >4 mcg/mL-eq or antibodies against infliximab >9 mcg/mL-eq identified patients who did not respond to an increased drug dosage with 90% specificity.” These patients were likely to benefit by switching to an alternative anti-TNF.

Related study: Clin Gastroenterol Hepatol 2015; 13: 539-47.  Trough levels of infliximab (>3 mcg/mL) at week 30 was associated with improved outcomes, including mucosal healing and corticosteroid-free remission.

Briefly noted from ImproveCareNow: Dotson JL et al. “Feasibility and Validity of the Pediatric Ulcerative Colitis Activity Index in Routine Clinical Practice.” JPGN 2015; 60: 200-04.  This study, with 2503 patients, found that the PUCAI was completed in 96% if visits.  The PUCAI correlated with PGA chain scores.

Related blog posts:

Don’t be Fooled About Withdrawing Immunomodulator Cotherapy -Look Past the Headline

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The coverage on a recent study (Clinical Gastroenterology and Hepatology 2015: 13(3): 514-521.e4) suggests that it should be fine to stop immunomodulator co-therapy.  I recommend reading the entire study (or at least this blog post)–you will probably come to a different conclusion.
Brief summary from AGA website: Withdrawal of Immuonomodulators after Co-therapy Does Not Reduce Trough Level of Infliximab in Crohn’s Patients

“The addition of immunomodulators increases the efficacy of maintenance therapy with infliximab for up to one year in patients with Crohn’s disease who have not been previously treated with immunomodulators. However, there are questions about the effect of withdrawing immunomodulator therapy from these patients. David Drobne and colleagues studied the effects of treatment with infliximab and immunomodulators (co-treatment) and then immunomodulator withdrawal on long-term outcomes of patients, as well as trough levels of infliximab and formation of anti-infliximab antibodies (ATI). Reporting in Clinical Gastroenterology and Hepatology, they find that, in a retrospective analysis, withdrawal of immunomodulators after at least six months (median, 13 months) of co-treatment with infliximab does not reduce the trough levels of infliximab in patients with Crohn’s disease. Detectable trough levels of infliximab at the time of immunomodulator withdrawal are associated with long-term response.”

Clinical Gastroenterology and Hepatology 2015: 13(3): 514-521.e4

Some additional details:

This was a retrospective open-label cohort study with 223 patients and median followup of 34 months. At baseline, 65 received infliximab (IFX) monotherapy and 158  received co-therapy with an immunomodulator (46 methotrexate, 112 thiopurine).  Immunomodulators were withdrawn “only in patients with durable response (ongoing clinical benefit with lasting disease control with low C-reactive protein [CRP] [below 10 mg/L]).”  Among the 158 on co-therapy, 117 reached a durable response and had withdrawal of immunomodulator after >6 months of combination therapy (median time 13 months).

Key findings:

  • At baseline, co-therapy patients, compared to monotherapy patients, had higher IFX trough levels (adjusted mean increase of 1.44-fold) and lower likelihood of antibodies to infliximab (ATI): 35/158 (22%) compared with 25/65 (38%), P=.01.
  • When immunomodulator was withdrawn, IFX levels remained stable: before 3.2 mcg/mL compared with after 3.7 mcg/mL. However, 45 of 117 (38%) required increasing doses of IFX and 21 of 117 (18%) discontinued IFX.
  • Trough levels of IFX and CRP  were most strongly associated with response to IFX dosing on monotherapy.
  • “Only 9 of 74 patients (12%) with detectable IFX trough levels at the time of immunomodulator withdrawal developed undetectable IFX trough levels during the subsequent follow-up.”
  • None of the 27 patients with IFX trough level >5 mcg/mL at time of immunomodulator withdrawal lost response to IFX during median follow-up of 29 months.

Though the headlines covering this article have suggested that IFX levels will stay stable when immunomodulators are withdrawn after >6 months, the authors proposed algorithm only recommends withdrawal for those with IFX trough level >5 mcg/mL.  In addition, the data showed that a large number of patients required dose escalation and/or lost detectable IFX levels. Despite their proposed algorithm to withdraw in this small group, the authors further backtrack in their conclusion:  “a prospective parallel group trial during a period of 5-10 years in a large group of patients is required to ascertain the real long-term benefit to risk ratio of continuing combined infliximab and immunomodulator treatment.”

Bottomline: If a patient is doing well, withdrawing immunomodulator co-therapy still has risks. I worry that the misleading reporting of this article will result in detrimental outcomes.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

Methotrexate Dosing in Dual Therapy

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A recent retrospective study (DOI: http://dx.doi.org/10.1093/ecco-jcc/jjv027 first published online: 23 January 2015 -reference from KT Park’s twitter feed) has suggested that high-dose methotrexate (MTX) (15-25 mg/week) is more effective than low-dose MTX (≤12.5 mg/week) as part of dual therapy for inflammatory bowel disease.

Here’s the abstract: Optimal Doses of Methotrexate

Background and Aims: Methotrexate is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease (IBD), however the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower dose and higher dose methotrexate with anti-TNF therapy among IBD patients.

Methods: Retrospective chart review was performed of 88 IBD patients at our center between 2010-2013. Low-dose methotrexate was defined as ≤ 12.5mg/week and high-dose methotrexate as 15-25mg/week. Patients who met the criteria for clinical remission (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) at baseline were followed for up to 42 months. Chart review occurred in six-month intervals. The primary outcome was consecutive months in remission prior to relapse. Secondary outcomes included other indicators of worsening disease (endoscopic inflammation, steroid use, therapy escalation/addition, or surgery) and adverse events. Regression analysis and Kaplan-Meier survival analysis were completed.

Results: We identified 73 (83%) dual-therapy patients, of which 32 low-dose and 14 high-dose individuals achieved remission. When compared with high-dose patients, low-dose patients were more likely to relapse (log-rank test, P<0.01). Secondary indicators of worsening disease occurred during 34.4% of low-dose review periods and 31.4% of High-dose review periods (P=0.67). 3/52 (6%) low-dose patients and 3/21 (14%) high-dose patients (P=0.34) discontinued methotrexate therapy due to adverse events.

Conclusions: When combined with anti-TNF therapy, methotrexate at doses of >12.5mg/week were more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients.

Related blog posts:

Emigration -One Way to Acquire Inflammatory Bowel Disease

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A recent study (Shitrit AB, et al. Inflamm Bowel Ds 2015; 21: 631-35) highlights the phenomenon of acquiring inflammatory bowel disease (IBD) by moving from a non-developed country to a developed country; the implication is that the changes in environment and diet predispose towards the development of IBD.

This study examined Ethiopian Jews who migrated to Israel.  Using a case-control study, the authors compared 32 Ethiopian immigrants to 33 Ashkenazi patients with IBD.

Key findings:

  • No Ethiopian immigrants had a positive family history compared with 42% of Ashkenazi group.
  • Crohn’s disease was more prevalent in the Ethiopian immigrants: 94% versus 73%.
  • The Ethiopian immigrants lived in Israel for at least 8 years before developing IBD an da median duration of 13 years.

The study discusses the difficulty of diagnosing IBD in rural Africa but speculates that rather than an underdiagnosis of IBD, it is likely to have a true low prevalence of IBD.

Take-home message: It takes many years for the environment exposures to allow for the development of IBD.  Additional work is needed to establish the clinical, genetic, and microbial factors that influence the acquisition of IBD in immigrants to developing countries.  Understanding the susceptibility of immigrants would have widespread application.

Related blog posts:

Withdrawing Therapy Leads To Relapse, Even if in Deep Remission

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A recent study, presented as an oral abstract (thanks to Jeff Lewis for forwarding this reference), indicates that even in patients in deep remission, withdrawal of anti-TNF therapy leads to relapse in about 50% even when thiopurines are continued; this is in agreement with previous posts (see below).

Full abstract: OP007 Relapse after Deep Remission in Crohn’s disease. Here are the results and conclusion from the abstract:

Results

Sixty one patients were included and followed-up for a median of 28 months (range 7-47). After withdrawal of anti- TNFa therapy (44 infliximab and 17 adalimumab) 47 (77%) patients continued thiopurines. 32 (52.5%) patients relapsed until the end of follow-up with a median time to relapse of 8 months (range 1-25). The cumulative probability of maintaining remission was 82% at 6 months, 59% at 1 year and 51% at 2 years. Analysis of 28 patients who were in deep remission (endoscopic healing; faecal calprotectin <150mg/kg; CRP <5mg/l) revealed no better survival (82%, 64% and 40% at 6 months, 1 and 2 years, respectively). Four (8%) of relapsing CD patients required surgery 5 to 19 months after anti-TNFa cessation (2 for new stricture development, 1 for medically refractory flare and 1 for high grade dysplasia). In multivariate model only disease localization was risk factor of disease relapse (colonic vs. ileal/ileocolonic: OR 0.16, 95%CI: 0.03-0.72; p=0.02). Type of anti- TNFa preparation, smoking, disease behaviour, corticosteroid or thiopurine therapy, biological markers and anti-TNFa trough levels did not impact disease relapse.

Conclusion

Approximately half of CD patients relapsed within 2 years after anti- TNFa discontinuation despite being in endoscopic remission when anti-TNFa was stopped. The highest relapse rate was observed during the 1st year. Ileal disease increased the risk of disease flare, while no other risk factor was identified.

Related blog posts:

Bryce Canyon

Bryce Canyon