Expanding Feeding Programs for Children with Autism

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.

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An Insurance Company Doing the Right Thing (with Calprotectin)

“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.

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“Tofacitinib: A Jak of All Trades”

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.”

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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?

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.

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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

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.

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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.

 

Combination Therapy Study Points to Central Role of Adequate Drug Levels

A recent study (JF Colombel et al. Clin Gastroenterol Hepatol 2019; 17: 1525-32) examines the effect of combination therapy and drug levels in achieving corticosteroid-free remission at week 26 (CSFR26).

The authors performed a post hoc analysis from 206 patients with Crohn’s disease (CD): 97 monotherapy with infliximab & 109 with combination infliximab/azathioprine

Key findings:

  • The proportions of patients achieving CSFR26 were not significantly greater among those receiving combination therapy vs monotherapy within the same serum infliximab concentrations
  • Mean trough infliximab concentrations in the combination therapy were higher than for monotherapy: 3.54 mcg/mL vs. 1.55 mcg/mL
  • Higher levels of antidrug antibodies were seen with monotherapy: 35.9% vs 8.3% of those with combination therapy.  Antidrug antibodies were detected only in those with lowest quartile of infliximab trough levels.

My take: This study indicates that combination therapy’s higher efficacy is due to  favorable pharmacokinetics rather than drug synergy.  If good infliximab trough levels can be achieved with infliximab monotherapy, this may obviate the need for combination therapy.  The uncertain factor is whether closer attention to trough levels will minimize the development of antidrug antibodies as effectively as the use of combination therapy.

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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.

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