Category Archives: inflammatory bowel disease

IPAA (Pouch) for Crohn’s Disease and Indeterminate Colitis

Posted on by

A recent review (S Chang, B Shen, F Remzi. Gastroenterology & Hepatology 2017; 13: 466-75 Full text link: When Not to Pouch: Important Considerations for Patient Selection for Ileal Pouch-Anal Anastomosis) makes recommendations regarding Ileal pouch-anal anastomosis (IPAA) for Crohn’s disease and indeterminate colitis. Key points:

  • In CD patients with isolated colitis and without perianal disease, “there were no differences in the rates of postoperative complications, pelvic sepsis, or pouch failure compared with UC patients” (GE Reese et al. Dis Colon Rectum 2007; 50: 239-50).
  • Rates of pouch retention for CD (Table 2) ranged from 43% to 94% in 19 studies. Most of these studies had small numbers (less than 40 patients). In the two largest studies with 97 patients and 150 patients, both with ~10 year followup, pouch retention rates were 74% and 87% respectively.
  • “Patients carrying the diagnosis of IC have pouch function on par with patients with UC, with no significant difference in the number of bowel movements…However, ..are more likely to develop CD of the pouch. Nevertheless, pouch failure rates among IC, IBD-unclassified, and UC are similar in multiple cohorts.”
  • Rates of pouch retention for IC ranged from 73%-100% among the 13 cited studies, though only 2 studies reported rates less than ~90%. The two largest studies with ~340 patients had retention rates of ~95% and followup of 3.4 yrs and 10.2 years.

This review also discusses IPAA and other issues including obesity (which increases the likelihood of complications), sphincter dysfunction, elderly patients, and radiation therapy.

Of note, recent ESPGHAN IBD Porto Group guideline for surgical Crohn’s disease management in children (J Amil-Dias et al JPGN 2017; 64: 818-35) at first glance seems to be at odds with Chang et al recommendations:

  • “Statement 8. Ileal pouch-anal anastomosis is not recommended when a patient has CD. (Agreement 100%)”
  • The body of the report is more nuanced: “There is, however, recent growing evidence that supports highly selective use of restorative proctocolectomy with ileal pouch-anal anastomosis for CD. These patients have isolated colonic CD and no evidence of ileal or perianal involvement.”

To me, statement 8 should have been worded to include “except in limited circumstances.”  As it stands now, it misleads those who do not carefully review the entire report.

My take: The report by Chang et al makes a strong case for its conclusion: “Although it is true that the diagnosis of CD is a potential contraindication to IPAA, patients with isolated Crohn’s colitis may thrive after pouch surgery.  At this time, patients with isolated Crohn’s colitis (without perianal disease or small bowel involvement) have good pouch retention rates.”  Their review prompted me to look more closely at the ESPGHAN IBD Porto Group guideline; their Statement 8 recommendation is, in fact, quite misleading.

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.

Keyhole view , looking into the Rotunda UVa, of Thomas Jefferson (or TJ for those in the know)

Calprotectin in Triaging Potential Pediatric IBD Cases

Posted on by

Thanks to KT Park’s Twitter feed for this reference: GA Holtman et al. JAMA Pediatr. Published online August 14, 2017. doi:10.1001/jamapediatrics.2017.1736

An excerpt from abstract:

Results  Of the 16 eligible studies, authors of 8 studies (n = 1120 patients) provided their data sets. All blood markers and fecal calprotectin individually significantly improved the discrimination between pediatric patients with and those without IBD, when added to evaluation of symptoms. The best marker—fecal calprotectin—improved the area under the curve of symptoms by 0.26 (95% CI, 0.21-0.31). The second best marker—erythrocyte sedimentation rate—improved the area under the curve of symptoms by 0.16 (95% CI, 0.11-0.21). When fecal calprotectin was added to the model, the proportion of patients without IBD correctly classified as low risk of IBD increased from 33% to 91%. The proportion of patients with IBD incorrectly classified as low risk of IBD decreased from 16% to 9%. The proportion of the total number of patients assigned to the intermediate-risk category decreased from 55% to 6%.

Conclusions and Relevance  In a hospital setting, fecal calprotectin added the most diagnostic value to symptoms compared with blood markers. Adding fecal calprotectin to the diagnostic workup of pediatric patients with symptoms suggestive of IBD considerably decreased the number of patients in the group in whom challenges in clinical decision making are most prevalent.

From: Inflamm Bowel Dis. 2017 Aug 16. doi: 10.1097/MIB.0000000000001202. [Epub ahead of print]

Vaccination and Inflammatory Bowel Disease -Resources Targeted for Adult Patients

Posted on by

From a recent Gastroenterology & Hepatology –Full Link:

Gastroenterology & Hepatology  July 2017 – Volume 13, Issue 7; Vaccination of Patients With Inflammatory Bowel Disease.  Francis A. Farraye, MD, MSc

Thanks to John Pohl’s twitter feed for this link that provides recommendations for Adults with IBD.

An excerpt:

G&H  What specific resources for vaccinations are available to help gastroenterologists?

FF  It is helpful for providers to keep a copy of the Crohn’s and Colitis Foundation’s health maintenance recommendations posted in their office. This 1-page checklist (available at http://www.crohnscolitisfoundation.org/science-and-professionals/programs-materials/ccfa-health-maintenance.pdf) includes all recommended vaccines and also comments on other important health maintenance items, such as screening for cervical and skin cancer, depression, and osteoporosis. In addition, Cornerstones Health has a vaccination checklist (available at http://www.cornerstoneshealth.org/wp-content/uploads/2017/06/Monitoring-and-Prevention-3.10.2017.pdf) that can be downloaded, printed, and placed in each examination room to reinforce the importance of vaccination. Primary care providers as well as gastroenterologists can use these checklists as reminders in their busy practices.

Related blog post:

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.

Two Viewpoints: Anti-TNF Therapy Shortly After Crohn’s Disease Surgery

Posted on by

A recent AGA perspectives issue provides two viewpoints on when to start/resume anti-TNF therapy after Crohn’s disease surgery:

Dr. Bressler states that he considers anti-TNF therapy for patients with ongoing immune dysfunction after surgery who are at high risk for recurrence.  Attributes of high risk disease include the following:

  • younger age (<30 years)
  • smoker
  • two or more surgeries for penetrating disease.

His commentary indicates that a “‘wait and see’ approach is appropriate for most patients. He frequently will measure a calprotectin three months postoperatively and every three months and perform a colonoscopy typically 6-9 months postoperatively. Those with endoscopic recurrence will be placed on anti-TNF therapy.

Dr. Requiero states:

  • The most effective way to prevent recurrence is to initiate an anti-TNF within four weeks of surgery. It has been my practice that patients at high risk for postoperative Crohn’s disease recurrence initiate anti-TNF shortly after they are discharged from the hospital.
  • If a patient had been on an anti-TNF prior to the surgery, I will usually resume the same anti-TNF after the surgery. In these patients, I do not give a re-induction course unless they had not received the anti-TNF for more than three months prior to surgery.
  • Concomitant therapy: “In the majority of patients, I treat with an anti-TNF, I will use a concomitant immunomodulator…One year after surgery, if there is no disease recurrence, I will decrease and often stop the immunomodulator. With the advent of therapeutic drug monitoring, I have a number of postoperative anti-TNF patients on monotherapy without an immunomodulator.
  • [In] patients at moderate risk for postoperative recurrence… I perform an ileocolonoscopy six months postoperatively and, if there is evidence of endoscopic recurrence, I add an anti-TNF agent. After finding a high rate of recurrence in these patients, I am beginning to shift my practice to initiating anti-TNFs in this moderate-risk group as well.

My take: I tend to favor Dr. Reguieiro’s approach in my patient population.

Related blog posts:

Pediatric Views on Biosimilars and Interchangeability

Posted on by

A recent commmentary (D Patel, KT Park. JPGN 2017; 134-6) explains the topic of interchangeability and its relationship to biosimlars. While biosimilars are expected to reduce the cost of biologic therapy, there are concerns regarding immunogenicity and whether switching to these products could reduce therapeutic sustainability.

The authors explain that some products are truly interchangeable and produce the same clinical result.  An interchangeable medicine (eg. typical generic) does not increase safety risk and switching from originator drug can be done by pharmacists or government payers without intervention of the prescribing health provider.

CT-P13 (Inflectra) has been approved as a biosimilar but has not been deemed an interchangeable product.  This is important.  Biosimilars “could have clinical consequences and repeated switches may increase immunogenicity.” Also, biosimilar products are much more complicated products than typical generic drugs.

Other key points:

  • The assumption that CT-P13 is interchangeable in pediatric IBD is “highly debatable.” Biosimilars undergo fewer studies than originator products.  CT-P13 has data from PLANETRA and PLANETAS trials “which may not be applicable for IBD, particularly pediatric IBD, given the inherent differences in disease pathophysiology.”
  • “No long-term, multiple-switch (eg. originator to biosimilar to originator) studies in pediatric or adult patients have been performed.”
  • “It is premature and possibly risky to assume that interchangeability will not cause differences in immunogenicity without long-term evidence in the pediatric population.” Pediatric patients likely have a “higher probability of developing autoantiantibodies” and need effective therapy for a longer duration.

My take: We still have a lot to learn.  Until more studies are available, switching stable patients could increase risk of losing response.

Related blog posts:

Dry Falls, Highlands NC

AGA Recommendations on Biosimilars

Posted on by

The AGA has made several recommendations regarding biosimilars –#2 and #6 are particularly of interest to pediatric gastroenterologists. More on this topic will follow tomorrow.

Link: AGA Makes Six Recommendations to FDA on Interchangeable Biosimilars

Related blog posts:

Pediatric IBD: Treating to Target

Posted on by

In 2014, an influential study by Sandborn et al (Clin Gastroenterol Hepatol 2014; 12: 978-85) described the importance of mucosal healing in a strategy termed “treating to target.”  The main findings (reviewed in a previous post Treating to Target) were the following:

  • Only half of the patients achieved MH.  “After a median follow-up of 62 weeks, 50.7% had MH and 61.1% had endoscopic improvement.”  79% of those who underwent adjustments achieved MH.
  • Clinical symptoms do not correlate with MH. “40.9% of patients experienced clinical symptoms despite MH and 18.8% of patients without clinical symptoms had significant endoscopic lesions.”
  • Biomarkers may be effective at predicting MH. “None of the patients with MH had an increased concentration of CRP.”
  • Adjusting treatment is needed if abnormal endoscopy; this is inherent in the philosophy of treating-to-target.

Now, my colleagues at Emory have published a single-center experience on mucosal healing (MH) (SL Santha, PR Shankar, A Pan, B Schoen, S Kugasthasan, CG Sauer. Inflamm Bowel Dis 2017; 23: 1447-53).  While this study has the typical limitations of a retrospective study, it makes several useful points.  It takes a little extra effort to interpret their findings as they describe their results based only on the 104 patients with clinical remission rather than based on the total of 182 patients who had at least two colonoscopies.  78 were excluded due to ‘acute GI symptoms.’

Of the 104 patients considered to be in clinical remission, 76 had Crohn’s disease and 28 patients had ulcerative colitis.

Key findings:

  • For patients with ulcerative colitis (UC) who were in clinical remission, 20 (71%) had MH per physician assessment, though only 10 patients (36%) had MH based on Mayo score of zero.  10 patients (36%) demonstrated histologic healing.
  • For patients with Crohn’s disease (CD) who were in clinical remission, 51 (67%) had MH per physician assessment, 34 (45%) had MH base on simple endoscopic score for CD, and 35 (46%) had histologic healing.
  • 21 of 25 CD patients and 8 of 8 patients with UC underwent escalation of therapy based on endoscopic evaluation. 9 patients underwent dose optimization of their biologic as the modification in their therapy; this step is now routinely done in pediatrics without followup endoscopy.

The discrepancy in MH rates based on physician assessment, endoscopic scores, and histologic healing is explained.  Generally, MH based on physician assessment would include normal and those with very mild mucosal disease.  “For CD, this included small and rare aphthous ulcers, and for UC, this included mild Mayo 1 erythema in only one segment of bowel.”

Questions about the approach to ‘treating to target:’

  • This study does not describe other alternative modalities to assess for mucosal healing. Is it feasible to use a biomarker like an abnormal calprotectin to target those in need of further evaluation? In those with abnormal biomarkers, dose escalation would not require a repeat scope.
  • The Emory group has used MRE extensively, but does not report MRE findings in this population.  Would MRE (which does not require sedation) be more useful in some patients?

As in adult patients, this study does show the need for objective markers in pediatric inflammatory bowel disease; 30% of patients who were considered to be in clinical remission had active disease with further investigation.  This finding has implications for ImproveCareNow which uses physician global assessment in tracking remission rates for pediatric IBD.

In their discussion, the authors state that “changes in medical therapy can increase the MH rate to nearly 80%, which could be even higher with additional changes in those who did not demonstrate MH on a second endoscopy.”  This sentence needs to be carefully interpreted.  The authors were able to show MH based on physician assessment in 82 of 104 patients (79%) who were in clinical remission.  This rate would be MUCH lower if the entire cohort of 182 were included, possibly no greater than 50%.

The authors conclude with “endoscopy should be considered in pediatric patients with IBD in clinical remission to identify those without MH who may require medication escalation despite the absence of clinical symptoms.”

My take: I agree with the authors that objective markers of clinical remission need to be obtained to assess the effectiveness of therapy.  However, I am not convinced that endoscopy is needed in every patient who is doing well on therapy; other biomarkers and imaging may be more beneficial.

Related blog posts:

Sign at Pisgah Fish Camp Restaurant: “On this site in 1897 nothing happened.”

 

 

Adalimumab Can Reverse Growth Failure in Pediatric Crohn’s Disease

Posted on by

In an industry-sponsored study (TD Walters et al. Inflamm Bowel Dis 2017; 23: 967-75), adalimumab (ADA) was shown to be effective agent in reversing growth failure associated with pediatric Crohn’s disease (CD).

Background:  About one-third of children and adolescents with CD suffer from growth failure and delayed puberty.  Several prior studies have shown that anti-TNF therapy can improve height velocity and that early treatment with anti-TNF therapy (≤3 months after diagnosis) leads to greater improvement in height obtained, if initiated before puberty or early into puberty. This study examines the effectiveness of ADA in children from the IMAgINE 1 trial.

The authors identified 73 participants with growth delays (& adequate data) along with 27 participants with no growth delays.

Key findings:

  • ADA therapy significantly improved and normalized growth rates at 26 and 52 weeks in patients with baseline linear growth impairment.
  • At week 26, height velocity z-score was 1.33 among 23 children in remission compared with -0.78 (n=29) among “nonremitters”
  • At week 52, height velocity z-score was 2.17 among 27 children in remission compared with -1.57 (n=17) among “nonremitters”

My take: In moderate to severe CD, anti-TNF agents have been demonstrated to reverse growth failure; though, this is expected to occur only in patients with clinical response. To my knowledge, no other CD medical therapies have been proven to reverse growth failure (surgical treatment can improve growth as well).

Related blog posts:

Quiet Spot on U Chicago Campus

Low Rate of Ocular Disease in Pediatric Crohn’s Disease

Posted on by

A recent study (S Naviglio et al. Inflamm Bowel Dis 2017; 23: 986-90) confirms that there is a low rate of ocular disease in pediatric inflammatory bowel disease (IBD); in this cohort, half had Crohn’s disease (CD) and half had ulcerative colitis.

In this single center study, 94 children with a median age of 13.4 yrs were offered ophthalmologic examination (2014-2016).  None of these patients reported ocular symptoms.  The authors assert that 70% had intestinal remission, though 64% had elevated fecal calprotectin levels (>100 mg/kg). Key finding: One patient (1.06%) had ocular finding of uveitis (previously diagnosed prior to study)

The authors indicate that hepatobiliary manifestations, present in 9, were the most common extraintestinal IBD manifestation (EIM). Arthropathy occurred in 8, cutaneous manifestations occurred in 6 and ‘metastatic’ CD occurred in 4.

My take:  Ocular disease is an infrequent EIM in pediatric patients with IBD.

Related article: K Hata et al. Inflamm Bowel Dis 2017; 23: 1019-24. This article found that patients with EIMs were more likely to have chronic pouchitis after colectomy for ulcerative colitis. Overall, chronic pouchitis developed in 3.3%, 7.6% and 16.6% at 2, 5, and 10 years respectively. Key finding: preoperative EIM yielded a HR of 4.52.