BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease of the
esophagus, characterized by esophagus-related symptoms and a dense tissue eosinophilia,
both refractory to proton pump inhibitors. Topical corticosteroids have proven effective in
inducing clinical and histologic remission. However, a long-term strategy for the management
of this chronic disease is not yet defined.
METHODS: In a randomized, double-blind, placebocontrolled,
long-term trial, we evaluated the efficacy of twice-daily 0.25 mg swallowed
budesonide in maintaining a remission in adult EoE with prior response to induction therapy.
Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically,
by immunofluorescence and by high-resolution endosonography. The primary end point
was the ability to maintain histologic remission (<5 eos/hpf) of EoE in. Secondary end points
were the efficacy on symptom control and on tissue remodeling as well as the determination
of the safety of long-term esophageal administration of topical corticosteroids.
RESULTS: During a 50-week therapy of quiescent EoE with low-dose budesonide the esophageal
eosinophil load (ECP staining) increased from 1.1 to 29.9 eos/hpf, but under placebo the
increase was significantly larger (0.5 to 51.1 eos/hpf; p=0.01). At the end of the studyperiod,
35.7% (5/14) of the budesonide patients were in complete and 14.3% (2/14) in
partial histologic remission; with placebo no patient was in complete and 28.6% (4/14)
were in partial remission (p=0.0647). The increase of the symptom score was markedly
lower in budesonide- (0.79 to 2.29 points) than in placebo-patients (0.71 to 4.00 points;
p=0.0875). The median time to relapse of symptoms was >125 days in the budesonide and
95 days in the placebo group (p = 0.14). Measured by high-resolution endosonography, all
EoE patients had pre-treatment a highly thickened esophageal wall compared with healthy
controls (3.05±1.08 mm vs. 2.18±0.35 mm; p<0.0001). Long-term topical budesonide
reduced mainly the thickness of the superficial wall layers (mucosa, 0.75 mm to 0.45 mm;
p=0.025) whereas the response of the deeper layers was less pronounced (submucosa 1.31
to 1.08 mm; p=0.19 and muscularis 0.82 to 0.76 mm; p=0.72). Budesonide did not evoke
any mucosal atrophy.
CONCLUSIONS: This study clearly demonstrates that 1) Untreated
eosinophil inflammation results in an impressive remodeling of the esophagus; 2) A therapy
is therefore needed; 3) The high relapse rate after short-term therapy requires a long-term
management and 4) Maintenance treatment with budesonide is well tolerated and keeps
half of the patients in remission.