Category Archives: Pediatric Gastroenterology Intestinal Disorder

Orodispensable Budesonide Tablets for Eosinophilic Esophagitis

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Full Text Link (courtesy of AGA twitter feed):Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial  AJ Lucendo et al. Gastroenterol 2019; 157: 74-86. https://doi.org/10.1053/j.gastro.2019.03.025

Abstract:

Background & Aims

Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE.

Methods

We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0–10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily).

Results

At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P< .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent.

Conclusions

In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

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Ustekinumab in Pediatric Clinical Practice

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A recent study (JR Dayan et al. JPGN 2019; 69: 61-67) provides some helpful insight into the use of ustekinumab.

Background: The authors conducted a retrospective review of 52 patients (73% younger than 18 years, 27% 18-21 years).

  • Median age at induction was 16.8 years.
  • 10 patients were biologic-naive; 42 had received at least one anti-TNF agent (18 had received two anti-TNFs).
  • 42 of the 52 patients had Crohn’s disease.
  • Of note, 64% of their patients had a normal baseline CRP and they defined “biomarker remission at 52 weeks” as having a normal CRP.  The high rate of normal baseline CRP likely indicates milder disease than many other refractory populations; though nearly half of the patients with Crohn’s disease were receiving steroids when ustekinumab was initiated.
  • Steroid-free remission was defined by Harvey Bradshaw Index ≤4 or partial Mayo Score <2 and off steroids for >4 weeks.

Dosing: 47 (90%) received induction with ustekinumab IV (260 mg if <55 kg, 390 mg if 55-85 kg, 520 mg if >85 kg) followed by 90 mg subcutaneous injections every 8 weeks

Key findings:

  • 75% of patients continued to receive ustekinumab at 52 weeks.
  • 50% of bio-exposed patients were in steroid-free remission
  • 90% of bio-naive were in steroid-free remission
  • 57% received a dose escalation (increased frequency due to inadequate clinical response); such that at 52 weeks, 12 were receiving q4 weeks, 9 were receiving q6-7 weeks, and 15 continued with q8 weeks.
  • With a median f/u of 18 months, the authors reported few serious adverse events: two patients had an anaphylactoid reaction with IV induction (Rx with steroids and epinephrine). One of these two went on to experience arthralgias, fatigue and headaches with maintenance injection and treatment was discontinued. One patient experienced “self-limited paresthesia of bilateral lower extremities at 16 months on therapy” (CHOP experience with 22 patients reported one case of transverse myelitis: #NASPGHAN17 More Abstracts)

Discussion:

  • The authors note low immunogeiecity of ustekinumab and “suggest that ustekinumab monotherapy is possible and preferable in children”
  • Limitations: Lack of better objective markers for response to treatment

My take: This data indicates that ustekinumab therapy was associated with clinical remission in 50% of patients who had received anti-TNF therapy and had higher response in a small sample of biologically-naive patients.  More experience is needed to confirm drug safety with long-term usage

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Barcelona

 

CDC Warns of Cryptosporidium in Pools

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July 1, 2019: Washington Post: CDC warns swimmers about ‘Crypto,’ a parasite that can live for days in pools

An excerpt:

The Centers for Disease Control and Prevention published a report last week about the increased number of outbreaks caused by the fecal parasite Cryptosporidium, more commonly known as “Crypto.”…

The warning came from the CDC’s recent Morbidity and Mortality Weekly Report, which highlighted an average 13 percent increase in cryptosporidiosis outbreaks each year from 2009 to 2017.

The CDC said that over the past decade, there have been more than 400 reported outbreaks in the United States, leading to nearly 7,500 people becoming sick. Of those, more than 200 people were hospitalized, and one person died as a result of the disease, according to the report…

In about 35 percent of the outbreaks, sicknesses were linked to swimming pools and playgrounds, according to the report.

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Bear and the Strawberry Tree, Puerta del Sol, Madrid

Vitamin D Supplementation Did Not Improve Postsurgical Outcomes in Patients with Crohn’s Disease

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Link from Kipp Ellsworth Twitter Feed: Healio Gastro: Vitamin D does not prevent Crohn’s recurrence after resection

Re: Duijvestein M, et al. Abstract 144. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Background: “Researchers conducted a placebo-controlled trial comprising 143 patients with CD to assess the potential anti-inflammatory effects of vitamin D. Patients were randomly assigned to receive either 25,000 International Units of vitamin D3 (n = 72) or placebo (n = 71) weekly for 6 months after their first or second ileocolonic resection.”

Key Finding: “While serum vitamin D levels increased in the vitamin D group and remained unchanged in the placebo group, investigators found no difference in the incidence or severity of endoscopic recurrence at week 26 between the two groups. Cumulative clinical recurrence rates at week 26 were also comparable.”

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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

Madrid view from Círculo de Bellas Artes

 

 

IBD Articles -Briefly Noted

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A Dige et al. Gastroenterol 2019; 156: 2208-16. This study evaluated the efficacy of freshly collected autologous adipose tissue injection for healing of perianal fistulas in Crohn’s disease.  The overall healing rate was 57% and the treatment had a good safety profile.

HK Somineni et al. Gastroenterol 2019; 156: 2254-65. The researchers found that DNA methylation patterns (from ~850,000 sites) in blood samples from pediatric patients with Crohn’s disease  (n=164) were associated with inflammation and resolved with treatment of inflammation; thus, the changes in DNA methylation are less likely to be a causative agent in disease development or progression and more likely a biomarker of inflammation.

OB Kelly et al. Inflamm Bowel Dis 2019; 25: 1066-71. Among 316 patients who underwent A/P CT scan for any reason, 49 (16%) had evidence of sacroilitis, indicating this is underdiagnosed in patients with IBD.

BG Feagan et al. Inflamm Bowel Dis 2019; 25: 1028-35. In a post hoc analysis of GEMINI 1 trial (n=769 patients: 149 placebo, 620 vedolizumab), a randomized placebo-controlled trial of vedolizumab for ulcerative coliis, compared to placebo ~40% more patients receiving a full induction of vedolizumab had a sustained clinical remission after 52 weeks of therapy.  Of patients in clinical remission at week 14, 66.5% achieved a sustained clinical remission at week 52 compared with 267% of placebo-treated patients based on partial Mayo score..  Sustained clinical remission was based on partial Mayo score and rectal bleeding subscore..

Best Approach for Identifying Eosinophilic Esophagitis

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A recent study (K Radicic, RF Stokes. Clin Gastroenterol Hepatol 2019; 1408-9) indicated that taking biopsies from three esophageal areas (proximal, mid, and distal)  improved the likelihood of identifying eosinophilic esophagitis (EoE).

Key findings:

  • In their study, among 96 patients with EoE, 55.2% were positive (>15 eos/hpf) in only 1 of the 3 levels.
  • 17 patients (17.7%) were positive in the mid-esophagus alone, and 6 patients (6.3%) were positive in the proximal esophagus alone.

The authors state that a 2-level biopsy protocol missed the diagnosis of EoE in roughly 1 of 5 patients.

My take: This study is provocative. However, the reasons why 3 levels improved their yield could be related to other factors rather than location.

  1. Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens
  2. Prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful.  Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.

My view is that if adequate numbers of biopsies are taken from several locations, a single jar for all the specimens should suffice (& reduce costs) –though a formal study could be beneficial to confirm this.

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From NASPGHAN 2014 EoE Slide Set

Is It Worse to Be Sitting at Work or Sitting at Home?

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A recent report indicates that sitting at home is more problematic for health than sitting at work and may be bad news for the manufacturer’s of standing desks.

Time: This Type of Sitting is the Worst for Your Health

Background: For the study, [published in the Journal of the American Heart Association: JM Garcia et al. Full text link Types of Sedentary Behavior and Risk of Cardiovascular Events and Mortality in Blacks: The Jackson Heart Study. https://doi.org/10.1161/JAHA.118.010406] “almost 3,600 African American adults reported the amount of time they’d spent sitting at work, watching television and exercising over the previous year. They also provided demographic, lifestyle and health-history information. The researchers monitored the participants’ health over eight years, during which 129 had a cardiovascular issue and 205 died.”

Key findings:

  • “After adjusting for health and lifestyle factors, the researchers found that “often or always” sitting at work was not associated with a heightened risk of death and heart disease”
  • “But those watching four or more hours of television per day had a 50% higher risk of heart issues and death, compared to those watching two hours or less per day.”
  • From Today: Sitting while watching TV, but not sitting at work, linked with higher health risk: “The health risk of watching lots of TV vanished when people spent 150 minutes or more per week doing moderate-to-vigorous exercise— like brisk walking, running, swimming and cycling.”

Commentary from Time report:

  • “People who spend a good chunk of their free time watching television likely do so at the expense of exercising.”
  • “Vegging in front of the TV may also inspire other unhealthy habits” –like snacking, consuming alcohol, and disrupting sleep patterns.

My take: This study suggests that sitting a lot at work is mainly a problem only for those who sit a lot when they leave work.

Retiro Park, Madrid

 

First Year of Life Antibiotics and Celiac Disease

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Briefly noted:

A recent study (SD Sander et al. Gastroenterol 2019; 156: 2217-29) found an association between antibiotics in the first year of life and celiac disease.

The authors “collected medical information on 1.7 million children, including 3346 with a diagnosis of celiac disease” using nationwide register-based cohorts from Norway and Denmark.

Key finding:

  • “Exposure to systematic antibiotics in the first year of life was positively associated with diagnosed celiac disease,” pooled odds ratio 1.26.  Furthermore, there was a dose-dependent relationship with increasing number of exposures increasing the risk of celiac disease.

My take: The increase in prevalence of celiac disease over that past few decades is likely related to changes in our environment.  These changes affect nearly everyone, but some are more susceptible to immune-related disease that may be triggered by these environmental changes.  This study shows that early exposure to antibiotics is likely to be one of the environmental factors that increase the risk of celiac disease.

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Retiro Park, Glass Palace
Madrid

Vedolizumab More Effective Than Adalimumab for Ulcerative Colitis

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Gastroendonews: Tea Leaves No More: Biologics Head-to-Head Produces a Winner

An excerpt:

In the first head-to-head trial of biologic treatments for inflammatory bowel disease, vedolizumab (Entyvio, Takeda) was nearly 50% more effective than adalimumab (Humira, AbbVie) in inducing clinical and mucosal remission in patients with moderate to severe ulcerative colitis…

They enrolled 771 patients with moderate to severe ulcerative colitis in the VARSITY study and randomly assigned them to receive 52 weeks of treatment with either vedolizumab or adalimumab…

They had failed other conventional therapies, including 25% in each group that had received an anti–tumor necrosis factor (TNF) agent…

  • 31.3% of vedolizumab recipients and 22.5% of those taking adalimumab were in clinical remission after 52 weeks (P=0.0061). Clinical remission was defined as a complete Mayo score of 2 or lower and no subscore greater than 1
  • Nearly 40% of patients who received vedolizumab achieved mucosal healing at 52 weeks, compared with 27.7% of adalimumab recipients (P=0.0005).

My take: This study provides a rationale for vedolizumab to be used as a first-line biologic agent for ulcerative colitis.

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Do Anti-TNF Agents Reduce Surgeries and Hospitalizations?

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Briefly noted:

A recent study (http://dx.doi.org/10.1136/gutjnl-2019-318440; SK Murthy et al. BMJ indicates that anti-TNF therapy has not been effective in significantly lowering CD-related hospitalizations or surgeries.

Full Text Link (from Eric Benchimol twitter feed): Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study)

My take: While big changes in the frequency of these outcomes were not demonstrated in this large study, prior studies, including the RISK study, have shown that anti-TNF therapy can be disease-modifying and reduce the risk of penetrating disease in Crohn’s disease.

Related blog post: CCFA Updates in IBD