ABSTRACT
Introduction (contexte de la recherche): In Parts A and B of the 3-part phase 3 LIBERTY EoE TREET study (NCT03633617), dupilumab 300 mg weekly (DPL qw) vs. placebo (PBO) demonstrated significant efficacy and acceptable safety up to 24 weeks (wks) in adults and adolescents with eosinophilic esophagitis (EoE). For patients (pts) who completed Parts A or B, Part C was an extended active treatment period for 28 wks. Objectif: To assess the safety and efficacy of DPL in pts who completed Part B and continued to Part C, up to 52 wks. Methodes: Of 80 DPL qw pts in Part B, 74 continued DPL qw in Part C (DPL/DPL). Of 79 PBO pts in Part B, 37 pts received DPL qw in Part C (PBO/DPL). Part B co-primary endpoints were proportion of pts achieving peak esophageal intraepithelial eosinophil (eos) count <= 6 eos/high power field (hpf) and absolute change from Part B baseline (BL) in Dysphagia Symptom Score (DSQ) score at Wk 24. Secondary endpoints included peak eos count, EREFS, and HSS grade and stage scores. In Part C, all co-primary and secondary endpoints were assessed at Wk 52 as secondary endpoints. Safety was also assessed. Resultats: Part B BL characteristics were similar across groups. At Wk 52 of Part C, 84.6% of DPL/DPL and 67.6% of PBO/DPL groups achieved peak eos count of <= 6 eos/hpf and mean (SD) absolute change from Part B BL in DSQ score was -30.26 (15.39) for DPL/DPL and -27.25 (11.46) for PBO/DPL pts. At Wk 52, peak eos count, EREFS, HSS grade and stage scores were reduced, compared with Part B BL, and EDP and T2 NESs were suppressed in DPL/DPL and PBO/DPL groups. Dupilumab demonstrated an acceptable safety profile in Part C;the most common (occurring >= 10%) treatment-emergent adverse events in DPL/DPL and PBO/DPL groups were injection-site reactions (13.5% and 10.8%), COVID-19 (9.5% and 10.8%) and nasopharyngitis (4.1% and 10.8%). Conclusion(s): As observed in Part A/C, dupilumab qw demonstrated persistent improvements in clinical, symptomatic, histologic, endoscopic and molecular features of EoE up to 52 wks and had an acceptable safety profile. PBO pts from Part B who received dupilumab in Part C showed similar efficacy to dupilumab qw pts of Part B.Copyright © 2023
ABSTRACT
Background Current therapies for pediatric and adult eosinophilic esophagitis (EoE) include dietary elimination, proton pump inhibitors, swallowed corticosteroids, and biologics. Our aim is to systematically assess the efficacy and safety of published randomized controlled trials (RCTs) of medical therapies for EoE that compare active treatments to placebo or to an active comparator. We consider RCTs that target the induction and maintenance phases of therapy, separately. Methods A search was designed by a Cochrane information specialist and included Cochrane Gut Register, CENTRAL, MEDLINE, Embase, and clinicaltrials.gov databases, from inception to May 2022. Studies that met our search criteria were imported into Covidence for title and review. All authors participated in study screening, and each study was independently evaluated by two authors. Reports of RCTs that met the inclusion criteria were selected for full text review. Multiple reports of the same RCT were collapsed into the parent study. Data from these studies was then extracted to RevMan Web to assess study characteristics, including study design, EoE definition, inclusion / exclusion criteria, age range, interventions, number of patients randomized, number of patients who completed the study, primary and secondary outcomes and conflicts of interest. Studies were also assessed for potential sources of bias including baseline imbalance, selection, performance, detection, attrition, and reporting biases. We used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess the overall certainty of evidence supporting the primary outcome. Results As of May 2022, we identified 2,638 reports that met our search criteria of which 14 were duplicates, giving a total of 2,624 reports that were imported into Covidence for further review. Following title and screening, 259 reports were selected for full text review, which were collapsed into 46 distinct RCTs that met the inclusion criteria. The primary outcomes for our systematic review were histological improvement, endoscopic improvement, and clinical symptom improvement, all as defined by the study at study endpoint, and withdrawals due to adverse events. The secondary outcomes of our analysis were serious adverse events, endocrine complications, growth concerns, infections, and health-related quality of life. Study outcomes were analyzed on an intention-to-treat basis. Risk ratios (RRs) and corresponding 95% confidence intervals (95% CI) are reported for dichotomous outcomes, and mean difference and standard deviation are reported for continuous outcomes. The data will be presented in full. Conclusions Results of this analysis inform clinicians about the efficacy and potential side effects of different medical therapies for EoE in both pediatric and adult populations. Deficiencies in our current knowledge will be highlighted and will provide direction for design of future RCTs in the field. Future research should continue to explore factors that influence initial and subsequent medical therapy selection for people with EoE.
ABSTRACT
Background: Although there is ongoing research into the effects of COVID-19 infection in patients with EoE, the non-infection-related impact of COVID-19 is not known. In particular, the impact of postponing endoscopy due to the pandemic has not been studied. Aim: To determine the impact of COVID-19-related endoscopy cancellations on clinical outcomes in EoE patients. Methods: In this retrospective cohort study, we identified adult patients with a diagnosis of EoE who had a routine endoscopy scheduled from mid-March 2020 to May 2020, the timeframe at the beginning of the pandemic when most procedures were stopped at our center. We determined if procedures were cancelled or proceeded, and if canceled, we determined which patients were rescheduled and returned. We extracted clinical, endoscopic, and histologic for the last procedure completed prior to the pandemic, and well as the next procedure performed during the pandemic, if a patient returned. Outcomes included histologic response (<15 eos/hpf), endoscopic severity (EREFS), and global symptoms response. Patients who had delayed care were compared to those who returned as scheduled. Results: Of 102 patients with an endoscopy scheduled within our time frame, 27 had the planned procedure and 75 were cancelled. Of these 75, 20 (27%) never returned for their EGD despite attempts to contact them. When compared to those who were cancelled, those who underwent their procedure had more severe fibrosis (predilation esophageal diameter 13.6 vs 15.1mm;p=0.04) and were more commonly treated with an elimination diet (56% vs 33%;p=0.04);the remainder of clinical features were similar (Table 1). For the 55 patients who were canceled but ultimately returned for their EGD, the mean time between procedures was 1.1±0.7 years. While treatment rates and endoscopic features were similar between the pre- and delayed post-COVID EGD, more patients required a dilation after their return (71% vs 58%;p=0.05) and their esophageal diameter had significantly decreased from the size achieved at the prior procedure (16.8mm to 15.0mm;p<0.001) (Table 2). Of 17 individuals who did not have stricture, narrowing, or dilation pre-pandemic, during their next endoscopy 5 (29%) had a stricture, 1 (6%) had a narrowing, and 7 (41%) required dilation. Conclusion: A large number of EoE patients had their endoscopies cancelled during the initial part of the COVID-19 pandemic. Those who were not cancelled had more severe fibrostenosis. Greater than 25% of those cancelled never returned for care, which is an unmeasured impact of the pandemic, and it is uncertain whether EoE findings have worsened in this group. Of those who returned, there was a delay of greater than one year, associated with progression of some fibrotic features and an increased need for esophageal dilation. (Table Presented) (Table Presented)
ABSTRACT
Background: The impact of COVID-19 infection on patients with eosinophilic esophagitis (EoE) and other eosinophilic GI diseases (EGIDs) is not known. Aim: To determine the characteristics of EoE and EGID patients who have COVID-19, assess severity COVID-19 in the EGID population, and evaluate for COVID-19-induced EGID flares. Methods: We established an online global registry (covideoeegid.org) where health care providers could report details of COVID-19 infection in EoE and EGID patients. The registry was publicized and reminders were sent via worldwide patient advocacy groups, professional organizations, and research collaborative groups. De-identified data were entered into the website related to patient demographics, EGID disease features and activity, comorbidities, and treatments. Data collected related to COVID-19 included source of exposure, symptoms, illness severity, hospitalizations, and deaths. Descriptive statistics were used to summarize the findings. Results: A total of 40 cases of COVID-19 in EoE/EGID patients were reported as of November, 2020 (Figure). Patients had a mean age of 25 (±11) years at the time of COVID-19 diagnosis, the majority were male (73%) and had atopy (73%), and nearly all (95%) had EoE, though some non-EoE EGIDs were reported (Table). At the time of COVID-19 infection, EGID disease activity was reported as in remission in 18 (45%) and moderate in 13 (33%). EGID treatments at the time of COVID-19 included PPIs (58%), swallowed/topical steroids (45%), and/or dietary elimination (42%) (Table). Most common exposures for COVID-19 were either unknown (30%) or from household contacts (30%);34 of the reported cases were confirmed with testing, while 6 were suspected based on clinical presentation. Common symptoms included cough (63%), fever (50%), anosmia (20%), and ageusia (18%);15% of cases were asymptomatic. No COVID-19 infections were classified as severe, and 32 (80%) were deemed mild (Table). Only 1 patient was hospitalized (received lopinavir and hydroxychloroquine), and no ICU admissions or deaths were reported. The mean number of days from infection to symptom resolution was 9.8±8.3. No EGID disease activity flares were reported due to COVID-19. Conclusions: In a global EoE/EGID registry, relatively few COVID-19 cases have been reported over an initial 8 month period, despite extensive efforts at outreach. The reported cases of EGID/COVID-19 are mild, with only one hospitalization and no deaths. Despite concerns of possible reporting bias and that EGID patients tend to be younger, based on this registry it does not appear that EGID patients are at increased risk for severe COVID-19 infection or that COVID-19 leads to EGID flares. Future serologic studies are needed to determine the prevalence of COVID in EGIDs. We ask providers to continue to report cases (covideoeegid.org). (Image presented) (Table presented)