A recent randomized, double-blind, placebo controlled study (Gastroenterol 2014; 147: 324-33) examined “high-dose” fluticasone propionate (FP) for patients, aged 3-30 years, with eosinophilic esophagitis (EoE). FP patients received 1760 mcg divided into two doses for three months, then the dose was reduced in half.
Efficacy: Among the 28 FP patients, a complete remission (CR) (≤1 eosinophil/hpf on histology) was evident in 65% compared with 0% CR in 14 placebo patients. Furthermore, partial response (PR) (multiple definitions of responsiveness -see Figure 2) evident in about 75%. Reduction in dose to 880 mcg/day resulted in 93% of EoE participants maintaining CR or PR.
Molecular response: The authors also studied the transcriptome prospectively in these patients with the “Eosinophilic esophagitis diagnostic panel” (EDP). “A large portion of the participants receiving FP in phase 1 showed a normalized signature compared with the dysregulated screening and placebo signatures….notably, the 6 FP participants with histologic PR or no remission also had a partial reversal with a signature different from the placebo group…However, there were still a few molecular nonresponders whose signatures failed to normalized upon FP treatment.”
Based on their study findings: the authors recommend assessment at 3 months after initiation of topical steroids because “extending the timeframe for high-dose FP to 6 months does not increase remission status.”
The authors could not identify any demographics or signs/symptoms that predicted response to high-dose FP. In addition, in this small cohort, no difference in adverse effects compared to placebo were found.
My take on this study is that it raises more questions than it answers.
- Is the higher induction dose of FP really needed or would 880 mcg/day over a 6 month period result in the same findings?
- Is FP superior to budesonide which is considered to have less systemic absorption?
- Should we be using higher doses of budesonide as well?
- Would patients be better off receiving systemic steroids and transitioning to topical steroids?
- What are the long-term consequences, good and bad, in using higher steroid doses?
Take-home message: In a carefully designed study with molecular correlation, higher doses of Fluticasone achieved high rates of complete remission in EoE patients. Except for elemental diets, no dietary therapies have shown to have a higher response rate.
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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.