#NASPGHAN19 Selected Abstracts (Part 1)

Link to full NASPGHAN 2019 Abstracts.

Here are some abstracts that I found interesting at this year’s NASPGHAN meeting:

NAFLD:

  1. Off-label use of topiramate may be helpful in stabilizing weight and improving NAFLD
  2. Socioeconomic barriers are frequent in NAFLD patients (the 2nd poster did not appear to show a control population):

Primary Sclerosing Cholangitis -Use of Vedolizumab for PSC did not appear to help

Eosinophilic Esophagitis

  1. EoE is four times more likely in this cohort with inflammatory bowel disease
  2. 2nd poster describes very early-onset EoE

Inflammatory Bowel Disease:

  1. Use of infliximab in VEO IBD.  Used in 46/122 (38% of patients) and 50% had persistent use 3 years later

Enteral nutrition –poster from our group describing good tolerance of plant-based formula (with Ana Ramirez).

Celiac disease.  This poster indicates low yield of additional serology for celiac disease besides TTG IgA and serum IgA. This includes testing in young patients (< 2 years) with celiac disease.

Two new drugs for obesity

Undoubtedly, a safe, effective medication for obesity would be a pharmaceutical blockbuster.  The record so far on previous medications has been dismal.  Many have been abandoned due to safety concerns, including sibutramine (myocardial infarction and stroke) as well as dexfenfluramine/fenfluramine (valvulopathy).  Two new FDA-approved agents have shown promise but caution in their use will be needed (NEJM 2012; 367: 1577-79).  Neither agent has approval for pediatric usage.

Belviq (lorcaserin) is a selective agonist of the serotonin 5-HT-2C receptor and Qsymia (phentermine with topiramate) is a combination sympathomimetic amine (anorectic agent) with an antiepileptic drug.

In studies with lorcaserin, three studies (1-year placebo-controlled) have shown that the number of patients losing >5% of body weight was increased compared to placebo.  Mean percentage body weight loss with lorcaserin was -5.8% in first two studies and -4.5% in third study.  In contrast, placebo patients who received lifestyle counseling lost  -2.5% and -1.5% respectively.  Overall, up to 47% of patients receiving medication lost more than 5% body weight.

Potential safety concerns with lorcaserin:  initially there were concerns due to increased incidence of tumors in rats and possible valvulopathy (eg. mitral or aortic valve regurgitation).  However, the FDA has concluded that it is unlikely that these are likely to occur in humans.

With phentermine/topiramate, two placebo-controlled studies have shown an increase in patients losing >5% of body weight compared to placebo.  In the first study, the mean percentage change in body weight was -10.9% combination (dosage 15 mg/92 mg) compared with -1.6% for placebo.  In the second study, this dosage led to a -9.8% reduction compared with -1.2% in placebo patients. Overall, up to 70% of patients receiving medication lost more than 5% body weight.

With regard to safety, it is known that topiramate is teratogenic and increases the risk of orofacial cleft.  Due to this, approval for this combination requires a risk evaluation and mitigation strategy (REMS) which permits only specially-certified pharmacies to dispense along with formal training for prescribers. In addition, this combination has been associated with mildly increased heart rate. Due to favorable changes in blood pressure, the FDA concluded that this medication had a good benefit-risk balance.  But, the manufacturer recommends against it use in patients with cardiac issues or cerebrovascular disease.

With both new medications, other safety concerns include the risk of increased psychiatric effects.  In addition, specific recommendations include the following:

  • Only recommended in adults with BMI ≥30 or adults with BMI ≥27 with at least one weight-related comorbidity
  • With both medications, if weight loss not adequate after 12 weeks then discontinue medication.  With lorcaserin, if weight loss is not ≥5%, then discontinue.  With phentermine/topiramate, if weight loss is not ≥3% at 12 weeks (with 7.5 mg/46 mg), consider dosage increase and/or discontinuation.

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