Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration.
In this double-blind, ...placebo-controlled, phase 3 trial, patients 11–55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire DSQ score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.
Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% 95% confidence interval (CI), 43.3%–59.1%; P < .001) or symptom response (52.6% vs 39.1%; Δ13% 95% CI, 1.6%–24.3%; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, –13.0 (SEM 1.2) vs –9.1 (SEM 1.5) (Δ–3.9 95% CI, –7.1 to –0.8; P = .015); EREFS, –4.0 (SEM 0.3) vs –2.2 (SEM 0.4) (Δ–1.8 95% CI, –2.6 to –1.1; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.
In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.
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Although endoscopy is a sophisticated technique for evaluating patients with gastroesophageal reflux disease (GERD), the single diagnostic test that enables the most comprehensive assessment for GERD ...is a well-performed video esophagram. Not only does the barium study permit assessment of morphologic abnormalities in the pharynx and esophagus, but also oropharyngeal swallowing function, esophageal motility, and gastroesophageal reflux. These factors are especially important for detection of anatomic findings such as strictures and hernias, for assessment of esophageal motility before and after fundoplication, and for excluding conditions that mimic GERD. Thus, esophagography and esophagoscopy are complementary procedures that provide a more comprehensive and therapeutically actionable plan for patients with GERD than either diagnostic test alone.
Background and Aims Previous estimates of incidence of intestinal metaplasia (IM) recurrence after achieving complete remission of IM (CRIM) through endoscopic therapy of Barrett's esophagus (BE) ...have varied widely. We performed a systematic review and meta-analysis of studies to estimate an accurate recurrence risk after CRIM. Methods We performed a systematic search of multiple literature databases through June 2015 to identify studies reporting long-term follow-up after achieving CRIM through endoscopic therapy. Pooled incidence rate (IR) of recurrent IM, dysplastic BE, and high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) per person-year of follow-up after CRIM was estimated. Factors associated with recurrence were also assessed. Results We identified 41 studies that reported 795 cases of recurrence in 4443 patients over 10,427 patient-years of follow-up. This included 21 radiofrequency ablation studies that reported 603 cases of IM recurrence in 3186 patients over 5741 patient-years of follow-up. Pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC after radiofrequency ablation were 9.5% (95% CI, 6.7-12.3), 2.0% (95% CI, 1.3-2.7), and 1.2% (95% CI, .8-1.6) per patient-year respectively. When all endoscopic modalities were included, pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC were 7.1% (95% CI, 5.6-8.6), 1.3% (95% CI, .8-1.7), and .8% (95% CI, .5-1.1) per patient-year, respectively. Substantial heterogeneity was noted. Increasing age and BE length were predictive of recurrence; 97% of recurrences were treated endoscopically. Conclusions The incidence of recurrence after achieving CRIM through endoscopic therapy was substantial. A small minority of recurrences were dysplastic BE and HGD/EAC. Hence, continued surveillance after CRIM is imperative. Additional studies with long-term follow-up are needed.
Background and Aims Data on the economic impact associated with screening for Barrett’s esophagus (BE) are limited. As part of a comparative effectiveness randomized trial of unsedated transnasal ...endoscopy (uTNE) and sedated EGD (sEGD), we assessed costs associated with BE screening. Methods Patients were randomly allocated to 3 techniques: sEGD or uTNE in a hospital setting (huTNE) versus uTNE in a mobile research van (muTNE). Patients were called 1 and 30 days after screening to assess loss of work (because of the screening procedure) and medical care sought after procedure. Direct medical costs were extracted from billing claims databases. Indirect costs (loss of work for subject and caregiver) were estimated using patient reported data. Statistical analyses including multivariable analysis accounting for comorbidities were conducted to compare costs. Results Two hundred nine patients were screened (61 sEGD, 72 huTNE, and 76 muTNE). Thirty-day direct medical costs and indirect costs were significantly higher in the sEGD than the huTNE and muTNE groups. Total costs (direct medical + indirect costs) were also significantly higher in the sEGD than in the uTNE group. The muTNE group had significantly lower costs than the huTNE group. Adjustment for age, sex, and comorbidities on multivariable analysis did not change this conclusion. Conclusions Short-term direct, indirect, and total costs of screening are significantly lower with uTNE compared with sEGD. Mobile uTNE costs were lower than huTNE costs, raising the possibility of mobile screening as a novel method of screening for BE and esophageal adenocarcinoma.
We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction ...study.
Induction full responders (≤6 eosinophils per high-power field eos/hpf and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS–BOS) or withdraw to placebo (BOS–PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS–BOS and BOS–PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia Dysphagia Symptom Questionnaire over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes.
The randomized withdrawal period enrolled 48 patients (BOS–BOS, n = 25; BOS–PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS–PBO than BOS–BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns.
For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.)
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Sound the Alarm for Barrett's Screening Sawas, Tarek; Katzka, David A
Clinical gastroenterology and hepatology,
04/2019, Volume:
17, Issue:
5
Journal Article
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