Category Archives: Pediatric Gastroenterology Intestinal Disorder

Non-Adherence Leads to Treatment Escalation and More on Early Infliximab Trough Levels

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Briefly noted: JK Carmody et al. AP&T 2019; first published 02 August 2019: https://doi.org/10.1111/apt.15445 Full text link: Longitudinal non‐adherence predicts treatment escalation in paediatric ulcerative colitis

In this cohort of 268 pediatric patients with ulcerative colitis in the prospective PROTECT study, non-adherence to mesalamine was associated with need for treatment escalation.

Key finding:

  • Declining adherence over time strongly predicted treatment escalation (β = −.037, P = .001). By month 6, adherence rate ≤85.7% was associated with treatment escalation.

As noted in a previous blog (Briefly noted: Induction Inflixmab Levels), a recent study (K Clarkston et al. JPGN 2019; 69: 68-74) identified target early infliximab trough levels for infliximab as≥ 29 for week 2 (infusion 2) and ≥18 for week 6 (infusion 3). Below is an associated figure:

Image courtesy of Michael Rosen twitter feed

IBD Briefs August 2019

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A Levine et al. Gastroenterol 2019; 157: 440-50.  This study found that a Crohn’s Disease Exclusion Diet plus partial enteral nutrition induced sustained remission in a 12-week prospective randomized controlled trial with 74 children.  At week 12, “76% of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given” EEN followed by PEN.  The associated editorial on pages 295-6 provides a useful diagram of various dietary therapy components for a large number of diets that have been given for IBD.  The editorial recommends:

“For now, simple dietetic recommendations such as consuming a well-balanced diet prepared largely from fresh ingredients and thereby avoidance of emulsifiers and additives and processed foods are appropriate for all patients.  In select patients,…a trial of dietary therapy alone with a diet such as CDED could be attempted for a short period of time, with close follow-up, and with agreement with the patient that failure to fully respond is an indication to escalate therapy.”  More dietary trials are ongoing.

Related blog posts:

NJ Samadder et al Clin Gastroenterol Hepatol 2019; 17: 1807-13. In this cohort from Utah 1996-2011 with 9505 individuals with IBD, 101 developed colorectal cancer.  Standardized incidence ratio (SIR) for CRC in patients with Crohn’s disease was 3.4, in ulcerative colitis 5.2, in patients with primary sclerosing cholangitis 14.8.  A family history of CRC increased the risk of CRC in patients with IBD to 7.9 compared to general population.  Family hx/o CRC increased the SIR by about double the CRC risk in IBD patients without a family hx/o CRC.

CR Ballengee et al. Clin Gastroenterol Hepatol 2019; 17: 1799-1806. In this study with 161 subjects from the RISK cohort, the authors found that elevated CLO3A1 levels in subjects with CD was associated with the development of stricturing disease but was not elevated in those with strictures at presentation and in those who did not develop  strictures.

AL Lightner et al IBD 2019; 25: 1152-68.  Short- and Long-term Outcomes After Ileal Pouch Anal Anastomosis in Pediatric Patients: A Systematic Review.  This review included 42 papers.

  • Rates of superficial surgical site infection, pelvic sepsis, and small bowel obstruction at <30 days were 10%, 11%, and 14% respectively.
  • Rates of pouchitis, stricture, chronic fistula, incontinence and pouch failure were 30%, 17%, 12%, 20% and 8% respectively with followup between 37-109 months.
  • Mean 24-hour stool frequency was 5.

MC Choy et al IBD 2019; 25: 1169-86.  Systematic review and meta-analysis: Optimal salvage therapy in acute severe ulcerative colitis.  Among 41 cohorts (n=2158 cases) with infliximab salvage, overall colectomy-free survival was 69.8% at 12 months.  The authors could not identify an advantage of dose-intensification in outcomes, though this was used more often in patients with increased disease severity, “which may have confounded the results.”

Hood River, OR

Blaming Reflux for BRUEs -Not Changing Despite Guideline Recommendations

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Briefly noted: DR Duncan et al. J Pediatr 2019; 211: 112-9.

In this retrospective cohort study of infants with brief resolved unexplained events (BRUEs) at Boston Children’s Hospital, the authors examined guideline implementation among 359 subjects in the year before and the year after AAP guidelines.

Key findings:

  • There were no significant changes in practice after guideline publication
  • Only 13% had videofluoroscopic swallow study performed; 72% of these showed aspiration/penetration
  • No subject had reflux testing, “yet reflux was implicated as the cause” for BRUE in 40%. Children continued to be “discharged on acid suppression despite lack of efficacy”

My take: The pendulum is (slowly) starting to swing back from blaming everything (including BRUEs) on reflux but this change is not evident in this study.

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Psoriasis Due to Infliximab –Latest Data

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Briefly noted: O Courbette et al. JPGN 2019; 69: 189-93. In a retrospective review, among 147 children with inflammatory bowel disease treated with infliximab (IFX) (123 CD, 24 UC), 20 patients (13.6%) developed psoriaform rashes.  14 of 20 were in remission when skin rashes (especially on scalp) occurred and rash developed at median of 355 days.  In this cohort, all were controlled by local steroids; no patients required IFX discontinuation.

Related blog posts:

Wahkeena Falls Trail, OR

Expanding Feeding Programs for Children with Autism

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A recent pilot (38 children) study (WG Sharp et al. J Pediatr 2019; 211: 185-92) examined the effectiveness of a less intensive feeding program to help children with autism and food selectivity.

Background:  Many children with autism are extremely picky eaters.

  • They may limit their diet to a ‘beige diet’ consisting of foods like chicken nuggets and fries.
  • They may insist on only pureed textures
  • They may demand only specific foods and limit to specific brands

To normalize these diets, typically intensive structured feeding programs are needed.  However, these types of programs are costly, and not available in all communities. Parental training though the MEAL (Managing Eating Aversions and Limited variety) Plan was studied by the authors.  This program consisted of 10 core and 3 booster sessions.

Key finding:

  • At week 16, positive response rates on the Clinical Global Impression Improvement scale was 47.4%for the MEAL plan compared to 5.3% in a control parent education plan.

My take: This pilot study shows that less intensive programs may be helpful in children with autism and feeding problems.  However, even with this more limited MEAL plan, a multidisciplinary team with a dietitian plan for each child along with behavior management strategies was needed.

Related blog posts:

Artwork near Krog Street Market

An Insurance Company Doing the Right Thing (with Calprotectin)

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“An Insurance Company Doing the Right Thing” –not The Onion headline this time.

Recently (April 7. 2019) United Healthcare put out a policy statement explicitly stating:

“Fecal measurement of calprotectin is proven and medically necessary for establishing the diagnosis or for management of the following:

  • Crohn’s Disease
  • Ulcerative Colitis”

Thanks to Kim Conn for identifying this policy.

The policy statement provides an in-depth rationale for why calprotectin is medically-indicated along with supporting recommendations from multiple GI societies and National Institute for Health and Care Excellence (NICE).  The policy statement includes a long list of references and would provide a strong argument in supporting calprotectin testing for all insurance providers.

Here’s the link: FECAL CALPROTECTIN TESTING United Healthcare.

Related blog posts:

Lots of lazy river floating. Deschutes River, Bend OR

“Tofacitinib: A Jak of All Trades”

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The clever title is derived from an editorial (KE Burke, AN Ananthakrishan. Clin Gastroenterol Hepatol 2019; 17: 1438-40) regarding three recent publications regarding Tofacitinib, a non-selective inhibitor of janus kinase (JAK) enzymes 1,2 and 3 which was FDA-approved in May 2018 for moderate to severe ulcerative colitis. This report was published prior to recent FDA warning regarding blood clots: FDA Warning on Tofacitinib

Two of the reports have been summarized previously on this blog:

The third study examines the safety of tofacitinib: W Sandborn et al. Clin Gastroenterol Hepatol 2019; 17: 1541-50

Methods: This study analyzed data from phase 2 and phase 3 trials with 1157 patients who had a median treatment of 1.4 years (1613 person-years).  More than three-fourths were receiving 10 mg BID.

Findings:

  • Serious infections were infrequent but there was a dose response relationship associated with herpes zoster infections.  At 10 mg BID,  the frequency was 5% whereas the rate was 1.5% in those receiving 5 mg BID and 0.5% in placebo-treated patients. This is likely related to interference of interferon production related to JAK inhibitor disruption.
  • Sandborn et al conclude that the “safety profile of tofacitinib for patients with UC appeared similar to that reported for patients with rheumatoid arthritis and for patients with UC treated with biologic agents, except for the higher incidence rate of herpes zoster infection.”

The editorial recommends NOT using tofacitinib for acute severe ulcerative colitis (ASUC); it “should be encouraged only in selected patients and preferably in the context of a research study.”  “Infliximab and cyclosporine [should be used] for steroid refractory UC;” however, they suggest that “one can consider initiating tofacitinib PRIOR to patients becoming steroid refractory.  “It could be used upfront on day 1.”

Related blog posts -Tofacitinib:

Related blog posts -ASUC:

Ciutedella Park, Barcelona

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.

Should Pediatric Patients with Celiac Disease Be Screened for Low Bone Mineral Density?

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A recent retrospective study (J Webster et al. Clin Gastroenterol Hepatol 2019; 17: 1509-14) with 673 children with newly diagnosed (biopsy-proven) celiac disease (CD) (median age 10.6 y) evaluated DXA studies at time of diagnosis.

Key findings:

  • Approximately 7% (n=46) had a low lumbar spine areal bone mineral density (aBMD) z-score (less than -2)
  • Of those with abnormal aBMDs, 18 had repeat studies.  11 of 18 normalized after institution of dietary management. Mean time for repeat DXA was 2.3 years
  • Of note, mean BMI z-score at time of repeat DXA was 0.005 (this includes 90 who had followup studies after a normal baseline DXA).
  • Low body mass index (BMI) with z-score of -0.4 identified a >10% risk of an abnormal aBMD

The authors acknowledge than DXA screening is controversial.  The current study’s strength is its large size.  Limitations include the inability to correlate with clinical factors including adherence to a gluten-free diet.

My take:

  1. Based on this study, it is likely that only 2-3% of pediatric patients with celiac disease will have a persistently abnormal DXA after institution of a gluten free diet for 2 years; it is likely that even more will improve with time if receiving appropriate dietary treatment.
  2. I am not likely to recommend obtaining a baseline DXA study in pediatric patients with newly diagnosed celiac disease; the treatment for low bone mineral density in the setting of celiac disease is the same as for all children with celiac disease.  If one were inclined to look for low BMD, optimal timing would likely be AFTER being adherent on a gluten free diet for at least two years particularly in those who had low BMI at presentation.

Related blog posts:

Columbus Monument, Barcelona

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

 

Briefly noted: Induction Infliximab Levels

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K Clarkston et al. JPGN 2019; 69: 68-74. This pediatric study with 72 children/young adults with Crohn’s disease examined infliximab trough levels; 70 received infliximab monotherapy & 88% received “standard” dose of 5 mg/kg

Key findings:

  • Infliximab level ≥18 mcg/mL at week 6 was strongly associated with clinical and biologic response as well as achieving an infliximab level ≥5 mcg/mL at week 14 (AUC 0.85).
  • A week 6 level ≥18 mcg/mL had 82% sensitivity, 82% specificity, 56% PPC, and 94% NPV  for having a therapeutic level at 4th infusion.
  • Median infliximab levels for clinical responders was 27.8 mcg/mL at 2nd infusion and 14 mcg/mL at 3rd infusion.
  • The authors reported that only 22% of their cohort achieved a week 14 infliximab level ≥5 mcg/mL. The median infliximab level at this time point was 2.1 mcg/mL.

My take: In this study, the standard dose of infliximab (5 mg/kg) was not adequate in ~80% of patients in achieving a therapeutic trough level.  If using the standard low-dose, it may be worthwhile to check a trough level prior to 3rd infusion or at week 10 to help determine if the level will be sufficient to start maintenance treatment at week 14 or whether an earlier infusion is warranted.

Related blog posts:

Barcelona

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.