IBD Briefs -October 2020

EV Loftus et al.  AP&T  2020; 52: 1343-1365. Full text: Long‐term safety of vedolizumab for inflammatory bowel disease

GEMINI long‐term safety (LTS) study results –initiated 2009:

  • Enrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks. Total of 7999 patient years of vedolizumab exposure.
  • Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients.
  • There were no new trends for infections, malignancies, infusion‐related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy
  • Conclusion from authors: “The safety profile of vedolizumab remains favourable with no unexpected or new safety concerns.”

Related blog posts:

AS Faye et al. Inflamm Bowel Dis 2020; 26: 1368-1376. Fertility Impact of Initial Operation Type for Female Ulcerative Colitis Patients (link includes video abstract)

Surgical options include Ileal pouch–anal anastomosis (IPAA), rectal-sparing colectomy with end ileostomy (RCEI), and ileorectal anastomosis (IRA). Conclusions based on “a patient-level state transition microsimulation in TreeAge Pro:”… “Despite an increased risk of infertility, our model results suggest that IPAA may be the optimal surgical strategy for female UC patients aged 20–30 years who desire children. For patients aged 35 years, RCEI should additionally be considered, as QALYs for RCEI and IPAA were similar.”   In older age group, RCEI’s increase rate of childbirth (28%), decrease time to childbirth (14 months) and 77% reduction in IVF are important factors.

Related blog posts:

R Tariq et al. Inflamm Bowel Dis 2020; 26: 1415-1422. Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease

In this retrospective study with 145 patients,  the overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. The authors concluded that “fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.”

Related blog posts:

Isle of Palms (July 2020)


Large Study Shows FMT Efficacy/Safety in Children

Clinical Gastroenterol Hepatol 2019. In press: Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children Thanks to Ben Gold for this reference.


Background & Aims

Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.


We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMTs at 18 pediatric centers, from February 1, 2004 to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.


Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.


Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.

Related blog posts:

Park Guell, Barcelona

Clostridium difficile and Inflammatory Bowel Disease

My view is that Clostridium difficile infection (CDI) in children with inflammatory bowel disease is often overdiagnosed due to detection of a carrier state in many when tested by PCR assays and the overlapping clinical features.  This is particularly important when considering fecal microbiota transplantation (FMT) due to the potential risks of this treatment.

Recently, I had a letter to the editor (J Pediatr 2018; 199: 283) on this topic that was accepted:

The author’s reply suggested that their approach followed IDSA guidelines by checking CDI with PCR in those who were clinically-symptomatic.  Yet, the IDSA guidelines (link here: IDSA C diff guidelines) do not focus on the issue of IBD flare-ups which cause identical symptoms.  Expert IBD specialists have recommended the following for identifying CDI in patients with IBD:

“Start with enzyme immunoassay-based tests with a reflex to PCR test for discordant enzyme immunoassay results.”  Rationale: “PCR is quite sensitive for the presence of toxigenic C difficile, it may increase the detection of asymptomatic colonization and shedding.” (K Rao, PDR Higgins. Inflamm Bowel Dis 2016; 22: 1744-54.)

Related blog posts:


#NASPGHAN17 Annual Meeting Notes (Part 2): Year in Review

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This first slide shows the growth in NASPGHAN membership:

Year in Review

Melvin Heyman  Editor, JPGN

This lecture reviewed a number of influential studies that have been published in the past year.  After brief review of the study, Dr. Heyman summarized the key take-home point.


Liver Briefs May 2017

Briefly noted:

O Jeanniard-Malet et al. JPGN 2017; 64: 524-7. This survey of 28 centers in France assessed clinical practice with regard to primary prophylaxis in portal hypertension. More than 75% use endoscopy to screen for varices in patients with chronic liver conditions. “In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation.”

Y-D Ren et al. Hepatology 2017; 65: 1765-8. FMT for chronic HBV? This small study with 5 patients who received fecal microbiota transplantation in an effort to clear HBeAg.  There were 13 controls.  Patients in both group received either ongoing entecavir or tenofovir antiviral therapy (& had received for at least 3 years). FMT was given every 4 weeks (1 to 7 treatments). HBeAg declined gradually after each round.  Three patients in the FMT arm cleared HBeAg compared with none in the control arm.  Two of the three cleared HBeAg after on FMT and the third after two rounds of FMT.

Y Sun et al. Hepatology 2017; 65: 1438-50.  In this report, the authors propose to augment the liver biopsy classification in patients with Hepatitis B.  Their goal is to provide more information about dynamic changes regarding fibrosis using three terms:

  • Predominantly progressive: thick/broad/loose/pale septa with inflammation
  • Predominantly regressive: delicate/thin/dense/splitting septa
  • Indeteminate

Using this new designation, they characterized 71 paired liver biopsies before and after entecavir for 78 weeks.  Before treatment: 58%, 29%, and 13% for progressive, regressive and indeterminate; after treatment: 11%, 11%, and 78% respectively.

Rodin Museum, Gates of Hell


How Much Do We Really Know About Fecal Microbiota Transplantation?

A recent study (SJ Ott et al. Gastroenterol 2017; 152: 799-811) followed 5 patients who were treated with a sterile fecal filtrate (via nasojejunal tube) for recurrent Clostridium difficile infection (CDI) for a minimum of 6 months.  This open-label study noted that this fecal filtrate transfer eliminated the symptoms of CDI in all 5 patients.

A summary of this important study is available in the AGA blog:

Here’s an excerpt: What is the Active Ingredient in FMT for CDI?

Stool was collected from 5 donors selected by the patients and fully characterized according to FMT standards. The stool was then sterile filtered to remove small particles and bacteria, and the filtrate was transferred to patients in a single administration via nasojejunal tube.

Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared….

They identified about 300 different proteins in each of the filtrates they analyzed—most proteins were of human origin, but the filtrates also contained 20–60 bacterial and fungal proteins. The major human proteins in the filtrate proteome were human enzymes such as intestinal-type alkaline phosphatase, chymotrypsin-like elastases, and α amylases. Bacterial proteins included metabolic enzymes and redox proteins without obvious microbiome-modifying properties, such as glyceraldehyde-3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, glutaredoxin-1, or thioredoxin-1…

Ott et al propose that the active component of FMT therapy might not be living bacteria, but bacterial components, antimicrobial compounds of bacterial origin (bacteriocins), or bacteriophages that contribute to a healthy intestinal microenvironment. These could be common to all successful FMT therapies and even rather unspecific regarding the bacterial strain(s) used for therapies. They propose that bacteriophages affect community dynamics of gut microbiota to resolve dysbiosis.

My take: This is a provocative study that challenges us to rethink how FMT works. Ultimately, treating CDI needs to be more precise.

Related blog posts:


Store Your Stool at OpenBiome

Due to concerns regarding disruption of a person’s microbiome and C diff infection, there is now an option to store your own stool –should it be needed to restore your ‘health’ microbiome.

Here’s a link to the Gastroenterology & Endoscopy News Report: OpenBiome Now Stores Your Stool

An excerpt:

Banking one’s own stool is a particularly good idea for individuals who have an elective surgery scheduled and for those who are predisposed to developing C. difficile infections, such as patients with inflammatory bowel disease, Dr. Kassam said…

“Just like banking one’s blood prior to surgery, one should be able to bank their stool in anticipation of antimicrobial exposure after admission to a hospital,” Dr. Brandt said. “This is of even greater importance in the immunocompromised patient who requires multiple courses of antimicrobials.”

Related blog posts:

Acadia Natl Park

Acadia Natl Park

October 2016: IBD Studies

Briefly noted:

E Zittan et al. Inflamm Bowel Dis 2016; 22: 2442-47.  In this study with 773 patients with history of ulcerative colitis/ileal pouch-anal anastomosis, there was no significant difference in complications/leak among the 196 with preoperative anti-TNF exposure (n=26, 13.2%) compared with the control group (n=66, 11.7%). Preoperative anti-TNF exposure does not appear to worsen outcomes after surgery.

C Hartman et al. JPGN 2016; 63: 437-444. This cross-sectional survey of 68 children with IBD (57 Crohn’s disease) found frequent nutrient deficiencies based on 3 day diet records.  Interestingly, children on exclusive enteral nutrition were much less likely to have inadequate intakes of energy, minerals, or micronutrients. This article provides plenty of reasons for children with IBD, particularly Crohn’s disease, to work with a nutritionist.

M Fischer et al. Inflamm Bowel Dis; 2016; 22: 2402-09. In a cohort study of 67 patients (35 with Crohn’s, 31 with ulcerative colitis, and 1 indeterminate colitis), fecal microbiota transplantation (FMT) for refractory Clostridium difficile infection was successful in 53 (79%) with a single infusion.  Four of the 14 failures, subsequently responded to anti-CDI antibiotics. Of the 8 who had a 2nd FMT, 6 were successful; and 1 of 2 responded to 3rd FMT.  Thus, 60 of 67 responded overall to FMT.  After FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%) and worse in 9 (13%).  In this cohort, 1 needed colectomy and 1 needed diversion.  This article indicates that FMT for CDI in IBD was associated with high cure rates and low risk of IBD flare.

A Khoruts et al. Clin Gastroenterol Hepatol 2016; 14: 1433-38. This was a study of 272 consecutive patients that underwent FMT for recurrent CDI. 15% had established IBD and 2.6% were determined to have IBD at time of FMT.  74.4% of IBD patients responded to a single FMT compared with 92.1% of patients without IBD.  More than one quarter of IBD patients experienced a clinical flare after FMT.

MA Conrad et al. Inflamm Bowel Dis; 2016: 22: 2425-31.  This review of early pediatric experience with vedolizumab in 21 subjects (16 with Crohn’s disease) identified a clinical response in 6/19 (31.6%) evaluable subjects at week 6 and 11/19 (57.9%) by week 22. Steroid-free remission was noted in 3/20 at 14 weeks (15%) and 4/20 (20.0%) at 22 weeks.  Overall, this shows a fairly low response rate to vedolizumab in this highly selected cohort.  Prospective pediatric studies of vedolizumab are needed to identify which patients are most likely to benefit.

University of Virginia Rotunda

University of Virginia Rotunda


FMT in the “Real World”

At DDW 2016, OpenBiome presented data (abstract Su1737) from 2,050 patients who received fecal microbiata transplants (FMT) in “the real world.”

Key findings:

  • Overall, 84% clinical cure rate with a single treatment
  • 85% of patients were treated with FMT via colonoscopy (250 mL) and 15% via nasal tube (50 mL). Nasal tube administration had a lower clinical cure rate of 77.9%, compared with 85.1% who had FMT via colonoscopy.

More information on this study: “Closet Thing to Miracle Cure”: Study Confirms Benefit of FMT in C difficile  Gastroenterology & Endoscopy News July 2016  This link also presents data on use of FMT in ulcerative colitis and the use of capsule FMT.

Related blog posts:

Lymphonodular Hyperplasia2

Final Tweets from #NASPGHAN15


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From debate regarding importance of mucosal healing:

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