Introduction

Reflux esophagitis (RE) is a common, chronic disorder characterised by the mucosal break with symptoms such as heartburn and/or acid regurgitation. Patient-reported outcomes (PROs) offer more comprehensive access to the symptoms and impact on RE, which is a widely used treatment option that is effective from the patient’s perspective. Vonoprazan is a novel potassium competitive acid blocker, approved in China for treating RE since 2019. Here, we present the PROs of vonoprazan in Chinese RE patients.

Aims & Methods

VIEW (NCT04501627) is a multicenter, single-arm, prospective, observational, real-world study to evaluate the safety and effectiveness of Vonoprazan. The subgroup analysis of VIEW was designed to assess the effectiveness of vonoprazan in patients with endoscopically confirmed RE. All patients were treated with 20 mg vonoprazan orally q.d. for 4 weeks (continued for 8 weeks if the patient did not show any beneficial effects) followed by a safety follow-up for 2 weeks. All the patients were assessed for symptomatic relief by PROs which included patient symptom diary (percentages of patients with complete relief of heartburn, nocturnal heartburn, regurgitation, and nocturnal regurgitation) and GERD questionnaire (GerdQ) scores.

Results

Out of 1040 endoscopy-confirmed RE patients, 935 (89.90%) patients were with mild RE (LA grade A/B) and 105 (10.09%) patients were with severe RE (LA grade C/D). For all RE patients with heartburn, night-time heartburn, regurgitation, and night-time regurgitation at enrollment, the percentages of patients with complete symptomatic relief during the first one-week of treatment were 35.1%, 47.2%, 29.5%, and 43.6% respectively; while during first two-weeks of treatment, the respective percentages were 60.7%, 71.3%, 52.3%, and 65.0%. Higher percentages were observed in patients with complete night-time heartburn or night-time regurgitation. Among subgroups, severe RE patients exhibited marginally higher percentages than mild RE patients (severe RE: 44.9%, mild RE: 33.7%), (severe RE: 52.2%, mild RE: 46.5%), (severe RE: 39.7%, mild RE: 28%) (severe RE: 47.1%, mild RE: 43.1%) during first one-week of treatment. A similar trend of symptomatic relief in severe RE patients was observed during the first two-weeks of vonoprazan treatment compared to mild RE patients (Table 1). The proportion of patients without typical GERD symptoms increased by 36.9% (95% CI: 32.79, 41.10), 36.7% (95% CI: 32.29, 41.09) and 39.3% (95% CI: 26.84, 51.78) for all RE, mild RE and severe RE patients, respectively, at week 4 compared to baseline. The total change in GerdQ scores from baseline to week 4 (mean (SD)) were −1.7 (2.76) (95% CI: −1.85, −1.48) in all RE, −1.6 (2.72) (95% CI: −1.81, −1.42) in mild RE and −2.1 (3.05) (95% CI: −2.72, −1.42) in severe RE, where negative value represents improvement in the symptomatic relief.

Table 1. Percentage of complete symptom relief after treatment for RE patients with symptoms at baseline

Conclusion

Vonoprazan exhibited quick symptomatic relief for both mild and severe RE patients in the real-world setting.

Disclosure

Funding statement: This study was funded by Takeda (China) International Trading Co., Ltd.
Acknowledgements: Medical writing support for the development of this abstract, under the direction of the authors, was provided by Tanushree Goswami PhD, Cr Swathirajan PhD, and Ravi Kiran PhD of Indegene Private Limited, Bangalore, India, funded by Takeda Pharmaceuticals, and complied with the Good Publication Practice 2022.
Conflict of Interest: Yinglian Xiao, Zhanxiong Xue and Xiuling Li have no conflicts of interest. Li Xie and Qi Song are employees of Takeda, and they hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.

Introduction

Symptom relief is the key treatment goal of gastroesophageal reflux disease (GERD). Vonoprazan, a potassium-competitive acid blocker approved in China, was superior in potency and duration of action versus conventional proton pump inhibitors in preclinical studies.¹ However, there are limited real-world data on the effectiveness and safety of vonoprazan in adult Chinese patients.

Aims & Methods

VIEW (NCT04501627) was a multicentre, single-arm, prospective, observational, real-world study conducted in China. Patients received 20 mg vonoprazan, orally, once daily for 4 weeks (8 weeks for insufficient healing), followed by a safety assessment of 2 weeks. In this post hoc subgroup analysis of patients with GERD, effectiveness was assessed, including changes in GERD-typical symptoms, GERD questionnaire (GerdQ) scores and complete relief in patients’ symptom diary.

Results

Among the 2214 patients included in the effectiveness analysis population of the GERD group, 86.7% were aged <65 years and 60.8% were male. Among evaluable patients with all-day heartburn (n=672) and all-day regurgitation (n=728) at baseline, 49.7% (95% confidence interval [CI], 45.9-53.6) and 40.8% (95% CI, 37.2-44.5), respectively, achieved complete symptom relief during the first 2 weeks of treatment. The reduction from baseline in all-day heartburn and regurgitation was significant (P<0.001) on days 1 through 14 of treatment. Among evaluable patients with night-time heartburn (n=746) and night-time regurgitation (n=816) at baseline, complete symptom relief was achieved in 59.9% (95% CI, 56.3-63.5) and 52.8% (95% CI, 49.3-56.3) of patients, respectively, during the first 2 weeks of treatment. The reduction from baseline in night-time heartburn and regurgitation was significant (P<0.001) on days 1 through 14 of treatment. The mean (standard deviation) overall GerdQ score improvement from baseline to week 4 was -1.6 (2.8). The percentage of patients without GERD-typical symptoms increased by 33.5% (95% CI, 30.7-36.3) from baseline to week 4. Symptoms of heartburn, regurgitation and sleep difficulties due to heartburn/regurgitation, and the need for additional medication generally reduced at week 4 compared with that at baseline (Table). Adverse events (AEs; any grade) were reported in 17.4% of patients in the safety population (N=2307), with the most common (>5%) being gastrointestinal disorders (8.3%). Overall, 0.9% of patients had ≥1 AE leading to study discontinuation. No AEs led to death.

Table: Improvement in symptom frequency score and additional medication usage from baseline to week 4 following vonoprazan treatment

Conclusion

This real-world subgroup analysis of Chinese patients with GERD demonstrated that vonoprazan effectively relieved symptoms, improved GerdQ scores and reduced the need for additional medications while maintaining an acceptable safety profile.

References

1. Matsukawa J, Inatomi N, Nishida H, et al. Nihon Yakurigaku Zasshi 2018; 152: 104-110.

Disclosure

Disclosures: This study was funded by Takeda (China) International Trading Co. Ltd. Yinglian Xiao, Xiuling Li and Yiyang Dai have no conflicts of interest. Kailun Liang and Li Xie are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honoraria from Takeda China, AstraZeneca China, Xian Janssen and Eisai China.
Acknowledgements: Medical writing support for the development of this abstract, under the direction of the authors, was provided by Adityadeb Ghosh, M. Pharm, of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd., an affiliation of Takeda Pharmaceutical Company, and complied with the Good Publication Practice Guidelines 2022.

Introduction

The primary treatment goals of gastroesophageal reflux disease (GERD) include resolving symptoms, preventing complications and symptom relapses, and healing erosive oesophagitis.^{1, 2} Heartburn and regurgitation are frequent and typical symptoms of GERD. Vonoprazan, a potassium-competitive acid blocker, is approved in China for the treatment of reflux oesophagitis.^{3, 4} However, there is a paucity of real-world data assessing the relief of typical daily symptoms achieved with vonoprazan in adult Chinese patients.

Aims & Methods

VIEW (NCT04501627) was a multicentre, single-arm, prospective, observational, real-world study conducted in China. Patients received 20 mg vonoprazan, orally, once daily for 4 weeks (8 weeks for insufficient healing). This post hoc subgroup analysis conducted in enrolled patients with GERD assessed changes in symptom scores for all-day or night-time heartburn and/or regurgitation during the first 14 days of treatment. A mixed-effects model for repeated measures assessed statistical differences in symptom scores from baseline for each day; least-squares mean (LSM) and its 95% confidence interval are reported (negative values indicate improvement).

Results

Among the 2214 patients included in the effectiveness analysis population of the GERD group, 86.7% were aged <65 years[A.G.1] and 60.8% were male. The LSM change in symptom scores from baseline demonstrated a significant improvement from day 1 of treatment in all-day heartburn and/or regurgitation, daytime heartburn or regurgitation, and night‑time heartburn or regurgitation (Table). Significant improvement continued to be observed on day 14 and throughout all previous days of treatment.

Conclusion

Vonoprazan provided rapid (from day 1), significant and durable symptom relief in patients with GERD.

Table: Improvement in symptom scores^a from baseline to day 14 of vonoprazan treatment (effectiveness analysis population; MMRM analysis)

References

1. Antunes C, Aleem A and Curtis SA. StatPearls. Treasure Island (FL), 2023.
2. Heidelbaugh JJ, Nostrant TT, Kim C, et al. Am Fam Physician 2003; 68: 1311-1318.
3. Xiao Y, Lu Y, Yang H, et al. Am J Gastroenterol 2023; 118: S345-S345.
4. Oshima T and Miwa H. J Neurogastroenterol Motil 2018; 24: 334-344.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Yinglian Xiao, Dekui Zhang and Jianyong Chen have no conflicts of interest. Kailun Liang and Li Xie are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honoraria from Takeda China, AstraZeneca China, Xian Janssen and Eisai China.

Introduction

Fexuprazan, a novel potassium-competitive acid blocker (P-CAB), is currently recognized as a successful alternative to proton pump inhibitors (PPIs) for acid-related disorders. However, its experience in the global market remains limited.

Aims & Methods

This study aimed to integrate two randomized phase 3 studies (NCT03736369 in South Korea and NCT05813561 in China) investigating the efficacy and safety of fexuprazan in subjects with erosive esophagitis (EE) across Asian populations, especially those with at least moderate severity of major symptoms (≥2 days of heartburn or acid regurgitation at baseline). The Cochran-Mantel-Haenszel method was used to assess the efficacy of fexuprazan 40 mg and esomeprazole 40 mg in treating EE and relieving major symptoms, whereas the Wilcoxon signed-rank test evaluated safety by testing changes in gastrin levels within each treatment group.

Results

Of the 595 randomized subjects, 513 (256 in the fexuprazan group and 257 in the esomeprazole group) were included in the efficacy analysis set (per-protocol set, PPS). In the PPS, the healing rates of EE in the fexuprazan and esomeprazole groups at weeks 4 and 8 were 86.90% and 84.00% (95% confidence interval [CI] = -2.80, 9.23) and 98.05% and 98.44% (95% CI = -2.30, 2.02), respectively. In the subgroup analysis of patients with at least a moderate severity of major symptoms (205 in the fexuprazan group and 197 in the esomeprazole group), the healing rates of EE did not differ between the two groups (week 4, 85.57% vs. 83.33% [95% CI = -4.70, 9.28]; week 8, 97.56% vs. 97.97% [95% CI = -2.84, 2.61]). However, the proportion of subjects without symptoms in the first 3 days in both full day and nighttime in the fexuprazan group was significantly higher than that in the esomeprazole group (20.44% vs. 11.90%, p = 0.0212 and 32.04% vs. 22.02%, p = 0.0387, respectively). In the safety set, serum gastrin levels at the final visit significantly increased by 87.23 pg/ml and 61.99 pg/ml from baseline serum gastrin levels in both fexuprazan and esomeprazole groups, respectively. However, the mean gastrin levels at the final visit in both groups did not increase to the clinically significant levels (121.89 pg/ml vs. 96.40 pg/ml, respectively). None of the observed increases in gastrin levels resulted in discontinuation of the study, and no significant safety risks were identified in either group.

Conclusion

The efficacy of fexuprazan in treating EE was not inferior to that of esomeprazole in Asian populations. In subjects with at least a moderate severity of major symptoms, symptom relief in the fexuprazan group was higher in the first 3 days, regardless of full-day or nighttime. In terms of safety, serum gastrin level was tolerable in both groups, and no serious adverse events occurred in the fexuprazan group.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated oesophageal disease that is showing a skyrocketing increase of new diagnoses in last two decades. Although tons of papers have been published clarifying several aspects of this disease, most of the evidences come from high volume – referral centres that may be not representative of the whole EoE population. In fact, little is known about demographic and clinical features as well as treatment outcomes of patients managed in community hospitals.

Aims & Methods

Between January 2021 and June 2023, we prospectively enrolled all EoE patients evaluated for the first time at two different centres: 1) a high-volume tertiary-care centre, the University Hospital of Padua (PH), that represent a national referral centre; 2) a low-volume community hospital, the hospital of Feltre (FH), with a catchment area of about 25,000 people, both located in the North-East of Italy. The diagnosis of EoE was made according to the latest international guidelines. Endoscopic features were assessed according to EREFS score (0-8 points). Histological remission was considered for eosinophilic peak <15 eos/HPF.
The main goals of our study were to compare the cohorts of EoE patients from a community and a tertiary care centre in terms of demographic and clinical features as well as to assess differences in the rate of histological response to medical treatments.

Results

Overall, 210 patients were consecutively enrolled, 177 (84.3%) in the tertiary centre (PH) and 33 (15.7%) in the community one (FH). We did not find any significant difference between PH cohort and FH patients regarding age (34.80 vs 38.24 years, p=0.193), male prevalence (79.1% vs 72.7%, p=0.491), body mass index (22.55 vs 22.63, p=0.906), prevalence of non-atopic comorbidities (35.6% vs 21.2%, p=0.158), diagnostic delay (3.35 vs 2.62 years, p=0.682). A not significant trend in higher EREFS score values was found in PH (3.3 vs 2.7, p=0.062). There was a significant difference regarding the number of patients that were evaluated for a second opinion (77% vs 15%, p<0.001) and the prevalence of atopic comorbidities (68.9% vs 42.4%, p=0.008), both higher in PH court.
Regarding medical treatments 184 patients were treated with PPI (157, 88.7% at PH and 27, 81.8% at FH, p=0.219). There was a significant difference in the rate of PPI response comparing PH and FH patients (29.94% vs. 51.85%, p=0.044). No differences in terms of rate of responsiveness regarding swallowed flixotide puffer (44% vs 36%, p=0.295) and orodispersibile budesonide (50.9% vs 61.5%, p=0.564).

Conclusion

This study elucidated several significant aspects regarding EoE. Firstly, it revealed that EoE patients treated in peripheral hospitals may exhibit a milder phenotype, characterized by less severe endoscopic features and fewer atopic comorbidities. Conversely, more complex cases tend to be referred to specialised centres, often seeking for a second opinion. Accordingly, the rate of PPIs responsiveness was found to be higher in community hospitals and, indeed, they still hold a significant as effective therapeutic option for EoE patients. Given that most of the evidence come from high-volume referral centres, it is crucial to keep in mind these differences when assessing the wide spectrum of EoE patients. Although the need for new therapies is still a fact, the increasing prevalence of EoE also necessitates a thorough evaluation of the financial implications of these drugs.

Introduction

Eosinophilic oesophagitis (EoE) is a chronic, progressive type 2 inflammatory disease. Proton-pump inhibitors (PPIs), swallowed topical corticosteroids (STCs), and elimination diets have been used as standard treatments for EoE patients. However, the real-world evidence (RWE) highlighting disease burden in Europe are limited.

Aims & Methods

To assess disease burden and treatment patterns among adolescent and adult patients with EoE in real-world practice.
Medical records were retrospectively reviewed for patients (aged ≥12 years) who were newly diagnosed with EoE between 1 January 2009 and 31 December 2019 (index) in Germany, France, Spain, and the United Kingdom. Patients with a peak eosinophil (eos) count (PEC) of ≥15 eos/hpf within 90 days of the index date and ≥1 follow-up endoscopy within 24 months of the index date were included. Demographics, clinical features, treatment patterns, and health outcomes were assessed from the 12-month pre-index period to the last medical record entry or death. Disease progression was assessed via physician-defined (based on symptoms, endoscopy findings, histology, need for dilation, and food impaction) and proxy-reported outcomes (dilation performed, strictures, dysphagia, evidence of food impaction, treatment initiation in treatment-naïve patients and switching/augmentation).

Results

Overall, 385 patients were included, with 70.1%–78.1% being male; the mean age was 27.8 to 33.9 years. At EoE diagnosis, the PEC was 35.3–46.1 eos/hpf, the endoscopic appearance of the oesophagus was abnormal in 73.7%–85.6% of patients, and dysphagia was present in 59.8%–82.8% of patients. Most of the patients across all 4 countries were treated with PPIs (61.5%–91.8%), STCs (56.7%–82.3%) and elimination diets (41.4%–55.2%) after EoE diagnosis. Of the patients with available data, abnormal histology (≥15 eos/hpf) was reported in 44.8%–72.0% of patients during the first 5 years after EoE diagnosis. The abnormal endoscopic appearance of the oesophagus was observed in 34.6%–83.3% of patients after approximately 2 years of EoE diagnosis and dysphagia was present in 10.2%–25.0% of patients after 4 years of EoE diagnosis across all 4 countries. While physician-defined disease progression occurred in 6.1%–16.1% of patients, 19.4%–35.1% of patients experienced proxy-reported outcomes of potential disease progression (including oesophageal dilation performed in 10.8%–21.7% of patients) after EoE diagnosis. An overview of patient and clinical characteristics at EoE diagnosis and treatment patterns and disease progression (physician-defined and proxy-reported) after EoE diagnosis across Germany, France, Spain, and the United Kingdom is provided in the Table.

Conclusion

Adolescent and adult patients with EoE chronically experienced substantial disease burden. A subset demonstrated disease progression, perhaps underrecognised despite treatment with PPIs, STCs, and elimination diets. Hence, successful EoE management may include proactive disease monitoring, treating underlying pathophysiology and prescribing maintenance therapies to achieve long-term clinical remission.

References

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Disclosure

Ulrike von Arnim: Consulting and/or speaker fees from Dr. Falk Pharma, Sanofi, Astra Zeneca, EsoCap, Abbvie, Janssen, Takeda, Pfizer, Bristol Myers Squibb.
Frank Zerbib: Consulting and/or speaker fees from Sanofi, Dr Falk pharma, Bristol Myers Squibb, Bioprojet, AstraZeneca.
Tiffany Pela, Juby A. Jacob-Nara, Gaelle Le-Bagousse-Bego, Sarette T. Tilton: Employees of Sanofi; may hold stocks and/or stock options in the company.
Bram P. Raphael, Amr Radwan, Ryan B. Thomas: Employees of Regeneron Pharmaceuticals, Inc.; may hold stocks and/or stock options in the company.
Rohan C. Parikh, Fareedat Bello: Employees of RTI Health Solutions, which received research funding from Sanofi to design and execute this study.
Funding: This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Acknowledgement: Medical writing support was provided by Akshata Rao and Ali Nasir Siddiqui, PhD, of Sanofi.