When seeing a new diagnosis of eosinophilic esophagitis (EoE), I often try to explain that there are two potential goals of treatment: clinical remission (improvement in symptoms) and histologic remission (improvement in appearance of esophagus with microscope). Unfortunately, these two outcomes are not always synchronous; more proof of this comes from a recent study (Clin Gastroenterol Hepatol 2012; 10: 742-49, 750-52 [editorial]).
In this double-blind, randomized, placebo-controlled study of fluticasone in adult patients with a new diagnosis of EoE, 19 patients were treated with fluticasone (880 μg BID) and 15 patients were treated with placebo inhaler –for six weeks. Initially, 21 patients were assigned to each group; 2 dropped out of treatment group and 6 dropped out of placebo group before completion of followup EGD. The average age in the treatment group was 37 years versus 38 years in the placebo group. A complete histologic response was defined as >90% reduction in mean eosinophil count; this occurred in 62% of fluticasone patients and in none of the placebo group, based on an intention-to-treat analysis. Another measure of eosinophil activity, eosinophil-derived neurotoxin (EDN), was reduced by 81% on intracellular staining in the treatment group compared with 8% in the placebo group. Figures 1 through 3 show this staining –it’s pretty cool!
Yet, the clinical response was not statistically different. Dysphagia was reduced by 57% in the treated subjects compared to 33% in the placebo subjects in an intention-to-treat analysis. Results were improved modestly in those who actually were treated: 63% (12 of 19) compared to 47% of placebo patients. A complete response for dysphagia was noted in 42.9% of fluticasone group compared with 28.6% of control group based on an intention-to-treat analysis. A fairly high rate of candidiasis was noted in treated patients 26%; no placebo patients developed candida.
Another interesting finding was that among those who continued PPIs for heartburn symptoms the response to fluticasone was not improved. 40% of PPI users had a complete histologic response compared with 79% of non-PPI users.
So what are the reasons for the discrepancy between clinical and histologic response?
- Established strictures and small-caliber esophagus may require dilation rather than medicines to relieve dysphagia
- Esophageal fibrosis and subsequent esophageal compliance may not respond to topical therapy or take a lot longer to improve
- Secondary candidiasis may reduce clinical response –though in this study, 5 of 6 patients with candida did in fact have symptom resolution
- Compensatory behaviors may improve clinical symptoms –chewing food, cutting up food better, drinking more fluids, and avoiding some foods. This may make it harder to detect important differences.
Patient information link: (Eosinophilic esophagitis – CCDHC Home)