A recent study (ES Dellon et al Gastroenterol 2017; 152: 776-86) provides more data indicating that a premixed solution of budesonide improves eosinophilic esophagitis (EoE). This study complements a recent report highlighted in a blog post earlier this year:
A Better Budesonide for Eosinophilic Esophagitis
In the present study by Dellon et al, the authors performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of 93 EoE patients (ages 11-40). All patients had dysphagia and active EoE. The active treatment group received 2 mg twice daily.
- Dysphagia symptom questionnnaire (DSQ) scores improved more in the active treatment group compared to placebo. At baseline, the DSQ scores were 29.3 and 29.0 respectively. After 12 weeks, the the scores were 15.0 and 21.5 respectively.
- Similarly, the active treatment group peak eosinophil counts improved more. At baseline, the treatment group had a count (per hpf) of 156 and this dropped to 39; in contrast, the placebo group started at 130 and dropped to 113.
- The overall histologic response (≤6 eos/hpf) was 39% for the treatment group and 3% for the placebo group.
- No significant adverse effects could be attributed to budesonide. There was 1 case of esohageal candidiasis. “There were no notable differences between the groups in cortisol levels.”
My take: Budesonide suspension is useful for EoE but not effective in all patients. A reliable composition from a manufacturer, if not too expensive, would be a big improvement for many kids with EoE. Higher doses of budesonide may be warranted in some cases of EoE.
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Statue outside the Louvre
A recent study (S Olivia et al. JPGN 2017; 64: 218-24) examines a preprepared viscous budesonide (PVB) for eosinophilic esophagitis (EoE).
The authors used higher doses than in previous studies: 1 mg twice a day if height <150 cm and 2 mg twice a day if height >150 cm. Treatment period was 12 weeks.
- 32 of 36 (89%) showed macroscopic remission at 12 weeks and median eosinophils count in histology dropped from 42.2 to 2.9 cells/hpf. 46.7% maintained remission (off therapy) at 36 weeks.
- 89% achieved eosinophil count <20 cells/hpf at 12 weeks.
- In this short study, the authors did not identify any changes in cortisol levels.
My take: A reliable composition from a manufacturer, if not too expensive, would be a big improvement for many kids with EoE. Higher doses of budesonide may be warranted in some cases of EoE.
Related article: “How I Approach the Management of Eosinophilic Esophagitis in Adults” I Hirano. Am J Gastroenterol 2017; 112: 197-99. (Thanks to Seth Marcus for this reference). The author states that he prefers to perform a baseline assessment prior to PPI initiation. After diagnosis, he will use PPI and if no response, advance to either a dietary approach or topical steroids (he prefers fluticasone using the diskus formulations). His goals for therapy include: elimination of esophageal eosinophilia (<5-15 eos/hpf), resolution of dysphagia, and maintenance of esophageal diameter ≥16 mm. He does advocate annual testing for adrenal insufficiency for those taking long-term topical steroids.
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A recent study (MC Golekoh et al. J Pediatr 2016; 170: 240-5) shows that adrenal insufficiency developed in 10% of patients on chronic (>6 months) swallowed corticosteroid therapy for Eosinophilic Esophagitis (EoE).
Background: 58 patients with 67% receiving fluticasone and 33% receiving budesonide. Median age: 13.7, median fluticasone dose 1320 mcg/day, median treatment duration: 4 yrs. For budesonide, median dose was 1000 mcg/day and median age 10.7 yrs.
Key findings with low-dose ACTH stimulation:
- Abnormal peak cortisol (≤ 20 mcg/dL) present in 15% and adrenal insufficiency (< 18 mcg/dL) (n=6) noted in 10%
- Only patients receiving >440 mcg/day of fluticasone had adrenal insufficiency
- No patients taking budesonide had an abnormal cortisol level
- Higher doses of fluticasone, particularly early in treatment, has been shown to have an improved inflammatory response. However, as with asthma therapy, higher doses increase the risk of adrenal insufficiency.
- Adrenal insufficiency can be asymptomatic but pose a risk for life-threatening adrenal crisis.
- Strengths of study: Fairly large cohort, endoscopic/pathologic reports available, and ACTH stimulation testing which has better sensitivity than random cortisol.
- Limitations: Lower number of patients receiving budesonide, particularly at a higher dose. No indication of adherence.
My take: If higher doses of fluticasone are needed for prolonged period, consider screening (endocrinology consultation) for adrenal insufficiency.
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Farjado, Puerto Rico
J Jimenez et al. (JPGN 2015; 61: 208-11) provide more data that gastric acid suppression is associated with an increase risk of Clostridium difficile infection (CDI). This was a retrospective case-control study with 138 children with CDI and 276 controls. After adjustment, acid-suppression therapy had a 1.8 Odds Ratio association with CDI.
S Harel et al. (JPGN 2015; 61: 190-3) in this retrospective ‘pilot’ study of patients receiving topical budesonide for eosinophilic esophagitis, 6 of 14 (43%) had mild biochemical evidence of adrenal suppression, as measured by ACTH testing. Bottomline: a prospective study is likely needed to confirm or refute these findings. In the meanwhile, stress steroid coverage could be considered in patients on prolonged budesonide.
A recent study (Sandborn WJ, et al. Gastroenterol 2015; 148: 740-50, editorial 701-4) shows that budesonide foam can be helpful for patients with ulcerative proctitis and ulcerative proctosigmoiditis.
Design: Two identical randomized, double-blind, placebo-controlled trials examined the use of budesonide foam in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Patients had at least 5 cm of involved mucosa but no more than 40 cm. Dosing: 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks. The primary endpoint of remission was defined as an endoscopy subscore of ≤1, rectal bleeding subscore of 0, and improvement or no change from baseline in stool frequency subscore of the Mayo score. It is noted that about 90% of patients had moderate Mayo endoscopy subscore at baseline.
- Combining the results of the studies, 41.2% achieved the primary end point of remission at the end of 6 weeks, compared with 24.0% of placebo patients.
- There were 10 patients (3.7%) with low morning cortisol (compared with 0.7% of placebo-treated patients) and 14% who had abnormal ACTH testing at 6 weeks (compared with 4% of placebo-treated patients), though there no reported signs/symptoms of adrenal suppression present.
The associated editorial suggests that budesonide could be implemented in patients who did not respond to 5-ASA topical therapy (suppository for proctitis and enema for proctosigmoiditis). In addition, the editorial questions whether a single night-time administration may be more effective by maximizing adherence.
Bottomline: Budesonide foam was superior to placebo in this study and may eliminate the need for systemic steroid use. As the editorial suggests, 5-ASA topical therapy likely should be considered as first-line treatment.
Related blog post: Budesonide for Ulcerative Colitis
A recent study (Wolf WA, et al. Clin Gastroenterol Hepatol 2015; 13: 45-58) examined 221 patients in a retrospective cohort study to determine how effective topical steroids were in the treatment of eosinophilic esophagitis (EoE). The authors studied these patients from 2006-2013; the majority received budesonide (63%) and the remainder received fluticasone; the typical dosing was 0.5 mg-1 mg twice daily and 440-880 mcg twice daily, respectively. 129 (58%) of the participants were >18 years.
- 57% had histologic response with <15 eos/hpf
- Refractory patients “were difficult to treat with dietary and second-line pharmacologic therapies, with less than half responding even after multiple second-line therapies.” The most successful second-line approach was diet: 6 of 16 (38%) had improved histology (<15 eos/hpf). Higher doses of topical agents were effective in 2 of 14 (14%) and alternative topical agent was effective in 2 of 7 patients (29%).
- Dilatation at the time of disease presentation (25% of the study cohort) correlated with poor clinical outcome. Only 40% (20 of 50) had a histologic response.
- High tissue levels of tryptase and eotaxin-3 increased the likelihood of a steroid response.
As this was a retrospective study, there were several weaknesses.
Take-home message: The findings from this large cohort show that more than 40% of patients did not have a favorable histologic response. Some recent studies indicate that higher doses of steroids may be effective, but this may be influenced by the proportion of individuals with advanced fibrostenotic disease.
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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.
A recent article (JPGN 2014; 59: 317-20) has shown that Neocate Nutra is a good alternative to splenda as a delivery vehicle for budesonide for children with eosinophilic esophagitis.
This retrospective review of 60 children treated with oral viscous budesonide (OVB) who used either splenda (n=46) or with Neocate Nutra (n=14). With regard to budesonide, in patients less than 10 years, the dose was 1 mg BID and older children received 2 mg/dose. For splenda patients, 10 packets were used to create a slurry whereas with Neocate Nutra powder the amount was 2.5 cm3 per milligram of budesonide. Followup endoscopy took place at least 10 weeks after the start of treatment.
- 13 of 14 Neocate Nutra patients achieved a histologic response (peak eosinophils <15/hpf) compared with 30 of 46 Splenda patients.
- Mean eosinophil count dropped from 62 to 9 for Neocate Nutra patients and from 59.5 to 25.5 for Splenda patients.
Limitations of study: small number, retrospective study.
Take-home message: Neocate Nutra is at least as effective as Splenda as mixture with budesonide. In addition, many parents may prefer to avoid Splenda.
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