IBD Shorts -March 2018

T Piester et al. Inflamm Bowel Dis 2018; 24: 227-34.  Stanford group published data on 49 patients which highlight the utility of a point of care (mobile) infliximab (IFX) dosing calculator: http://med.stanford.edu/gastroenterology/infliximab-calc/  In their cohort, the IFX calculator recommendations were for IFX dosing escalations in 13% of the 222 calculations.  Overall, the IFX calculator was part of a larger quality initiative (QI) to achieve therapeutic drug levels >5 mcg/mL which occurred in 81% during the QI period.

JC deBruyn et al. JPGN 2018; 66: 268-77. This was a retrospective review of infliximab (IFX) in pediatric Crohn’s disease with 180 children. The authors determined that IFX had good therapeutic durability with 91% remaining on IFX after 2 years of treatment.

FS Macaluso et al. Inflamm Bowel Dis 2018; 24: 394-401. In this 2-year study, among 630 patients, 46 had a modestly-dosed immunomodulator added to anti-TNF therapy due to loss of response (31 to IFX or biosimilar, 10 with adalimumab, and 5 with golimumab).  This resulted in a steroid-free remission in 15 (32.6%) and a clinical response in 6 (13.0%). The immunomodulators were azathioprine in 15, 6-mercaptopurine in 5, methotrexate in 20, and mycophenolate mofetil in 6. The median doses for immunomodulators were 1.64 mg/kg/day, 0.84 mg/kg/day, 15.6 mg/week, and 1500 mg/day respectively.

C Reenaers et al. Clin Gastroenter Hepatol 2018; 16: 234-43. This retrospective study examined 7-year outcomes from a STORI cohort of 115 adults with Crohn’s disease (CD) with combination therapy who had infliximab withdrawal after achieving sustained remission. Among those restarting infliximab, treatment failed in 30.1%; 70.2% “had no failure of de-escalation strategy.” Major complicatins occurred in 18.5% of patients. Risk factors for failure included anemia (Hgb <12.5), increased white blood cell count >5.0, and upper GI location of CD.

VM Merrick et al. JPGN 2018; 66: 274-80.  This UK “real-life” review of 37 centers and 524 patients (429 with Crohn’s disease) found a remarkably poor rate of documentation.  They could determine the remission rates in only 71 of these patients (65% 46 of 71).  Thus, in the real-world, presumably in adults and children, most institutions do not know their remission rates.  While the determination of remission still relies on imperfect measures, the centers who participate in ImproveCareNow have high documentation rates –this is also a real-world experience as more than 29,000 patients and more than 900 pediatric GI doctors participate.


Esophageal Diseases Special

Gastroenterology published a ‘special issue’ in January 2018 (volume 154; pages 263-451) which reviewed several esophageal diseases in-depth: gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and esophageal cancer. For me, this issue served as a good review on GERD and EoE.

A couple of items that I picked up:

  • For both GERD and functional dyspepsia, “estimated prevalence values are approximately 20% for each.” (pg 269)
  • “15% of healthy individuals may have microscopic esophagitis” (pg 291)
  • For pH-impedance, the current view of non-acid reflux is unchanged: “unknown clinical relevance of non-acid reflux in the setting of aggressive acid suppression.” (pg 291)
  • Treatment algorithm for EoE (pg 353):
    • Induction treatment with any of the three approaches:  high dose topical corticosteroids, double dose proton pump inhibitor (PPI) or elimination diet “because no comparative studies have shown any of these to be superior to the others.”
    • Then, re-evaluation after 2-3 months (clinical, endoscopic, and histologic).  Responders should continue on therapy but maintenance treatment suggests low dose topical corticosteroid, lowering PPI to single dose, or continuing elimination diet.  For nonresponders, switching to one of the other two treatment approaches is recommended.
    • The algorithm indicates that followup evaluation of responders to insure ongoing response should be considered 1 year later
  • As for dilatation, the authors note that this does not control the underlying inflammation and thus should not be used as monotherapy. Also, “after dilatation, 75% of patients have considerable chest pain that may last several days.” (pg 354)

Unrelated twitter post below -IgG allergy testing is NOT a good idea:

Cost Effective Fecal Transplantation

A recent retrospective study (DE Brumbaugh et al. J Pediatr 2018; 194: 123-7) examined the effectiveness of intragastric fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI) in 42 children (47 FMTs).

Key findings:

  • 94% (16/17) success in otherwise healthy children
  • 75%  (9/12) success in medically complex children
  • 54% (7/13) success in inflammatory bowel disease.
  • Figure 2 describes cost: nasogastric FMT cost for hospital/professional charges was $1139 compared to $4998 for nasoduodenal FMT and $7767 for colonoscopy FMT

To understand the results better, one needs to look at their methods.  The authors defined CDI based on a positive fecal polymerase chain reaction (PCR) test.  All patients undergoing FMT had to have had >2 episodes of CDI.

The authors discuss the issue that asymptomatic Clostridium difficile carriage is common in IBD (“6 times that in healthy controls”) and the fact that true CDI can be difficult to ascertain as the relative contribution of IBD activity can be difficult to separate from CDI.  Interestingly, the authors did not comment on their use of PCR testing to establish infection.

As noted in a previous blog post (Overdiagnosis of Clostridium difficile with PCR assays), immunoassay testing for toxin is likely helpful in equivocal cases.  In an influential JAMA Intern Med study (JAMA Intern Med. 2015;175(11):1792-1801.  doi:10.1001/jamainternmed.2015.4114), virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method.

Other useful points in this study:

  • The authors note that craniofacial anatomy may preclude NG placement in some patients (in some orogastric insertion could be an alternative)
  • Patients at high risk for GERD/aspiration along with general anesthesia patients are “not good candidates for FMT”
  • “If there is concern for undiagnosed IBD or other GI pathology, FMT via colonoscopy may be preferable” as FMT could be diagnostic and therapeutic.

My take: This study confirms the utility of intragastric FMT for recurrent CDI as a cost-effective option.  More careful examination of CDI in patients with IBD could result in determining which patients are most likely to benefit from FMT

Hoover Dam


Related blog posts:

What Should an Aerodigestive Program Look Like

A recent “consensus statement” publication (Boesch RP, et al. Pediatrics 2018; 141: e20171701) discusses the structure and functions of an aerodigestive program. Congratulations to Dr. Ben Gold –one of my partners and a coauthor.

Overall this is a useful document and a good starting point to establish what an aerodigestive program should look like.

  • Table 1 lists common conditions addressed by aerodigestive programs like chronic cough, Gtube dependence, failure to thrive, TEF/esophageal atresia, recurrent infections, craniofacial anomalices, tracheostomy dependence, vocal cord dysfunction, stridor and wheezing.
  • Table 2 lists important team members.
  • Table 3 establishes important functions like care coordination, combined endoscopy, and summary of recommendations.
  • Table 4, 5, and 6 summarizes procedural skills needed by pulmonology, gastroenterology, and ENT respectively.

The accepted definition of an aerodigestive disorder: “A pediatric aerodigestive patient is a child with a combination of multiple and interrelated congenital and/or acquired conditions affecting airway, breathing, feeding, swallowing, or growth that require a coordinated interdisciplinary diagnostic and therapeutic approach to achieve optimal outcomes.”

  • The authors were split on whether the care needs to be provided by all providers in the same space or whether coordination can occur with separate physician locations.
  • The authors argue that coordinated care is valuable, citing care in children with cystic fibrosis and inflammatory bowel disease (via ImproveCareNow).
  • They note the major limitation is that their recommendations are based on expert opinion.

My take: My main concerns with multidisciplinary care, having participated in a number of multidisciplinary teams, are the following:

  1. There is a lot of redundancy in care with these clinics.  Often, these clinics result in a patient having two GIs, two pulmonologists, and two ENTs. If the aerodigestive team is useful, the aerodigestive expertise needs to be substantially greater than the expertise of their colleagues.  If it is simply a matter of care coordination, this is a deficiency that could be corrected in the absence of a multidisciplinary team.
  2. Many patients do not need all of the multidisciplinary team members. This increases costs unnecessarily.
  3. The potential promise of care coordination is sometimes offset by the extremely lengthy visits at multidisciplinary visits.

So in my view, the key for aerodigestive clinic success is to identify a narrow population of children with high-complexity problems and to identify subspecialists with exceptional abilities.  As an aside, the study states that Cincinnati was the first location to establish a pediatric aerodigestive clinic.  The success there was in large part due to Dr. Colin Rudolph (GI) and Dr. Robin Cotton (ENT), both recognized leaders and innovators in their fields.

Tunnels and hallways inside Hoover Dam

Predicting Response to Vedolizumab and Ustekinumab for Inflammatory Bowel Disease

A recent review (A Barre, JF Colmbrel, R Ungaro. Alim Pharm Ther 2018 DOI: 10.1111/apt.14550) discusses predictors of response to vedolizumab and ustekinumab for inflammatory bowel disease (IBD). Thanks to Ben Gold for this reference.


  • “Vedolizumab is a humanised monoclonal gut-selective antibody against α4β7 integrin and inhibits the trafficking of inflammatory cells to the intestine.”
  • From Vedolizumab GEMINI trials, , “primary response to vedolizumab was typically evaluated at week 14 after induction with rates of clinical remission and clinical response ranging between 24%-36% and 49%-64% in CD, and 23%-39% and 43%-57% in UC, respectively”
  • “Ustekinumab is a monoclonal IgG1 antibody against the p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23) that targets both the T-helper 1 and T-helper 17 pathways involved in the pathogenesis of CD.”
  • With Ustekinumab, “in real-world observational studies, patients were treated off-label and received highly variable induction and maintenance dosing, thus limiting the generalizability of results. The rates of response were reported to be as high as 84% and remission rates as high as 35% at end of induction, with loss of response in around one-third of patients during maintenance”

Key points:

  • Patients with severe disease (by clinical activity and inflammatory biomarkers), and prior anti-TNF exposure are less likely to respond to vedolizumab.
  • Ileocolonic disease, no prior surgery and uncomplicated phenotype were associated with better responses to ustekinumab in CD

With ustekinumab, in particular, there is still very limited data on its effectiveness and long-term outcomes and this is even more the case in pediatrics. This review does a good job in compiling the current available data.

My take: While this is a nice review, it does not help me much with developing an algorithm for how I will use these relatively new medications for IBD.

Related blog posts:

Bright Angel Trail

Oats OK in Celiac Disease

A recent double-blind, randomized, placebo-controlled trial (E Lionetti et al. J Pediatr 2018; 194: 116-22) examined the effect of adding oats to the diets of 79 children and compared this to a control group of 98 children; all participants had biopsy-proven celiac disease (CD).


  • “A large body of evidence has so far suggested that the consumption of pure oats is safe in the vast majority of patients with celiac disease.”
  • Still concerns persist.  In addition, the purity of oats cannot always be guaranteed.
  • Previous studies were limited by small sample sizes, short follow-up, limited details regarding oat used, and lack of detail about cross-contamination.

This study sought to remedy prior trial deficiencies and examined clinical indices,  serology, and intestinal permeability after 6, 9 and 15 months.

Key finding:

  • There were no statistically significant clinical, serologic, or intestinal permeability variables when comparing the oat group to the control group.

My take: Oats, free of cross contaminants, are safe to incorporate into a gluten-free diet for CD.

Canyon Rim

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.