Introduction

Systemic sclerosis (SSc) is a rare and complex autoimmune disorder characterized by fibrosis of the skin and internal organs, as well as vasculopathy. The disease can be classified into two main subtypes: diffuse and limited. The diffuse subtype is more frequently associated with significant internal organ fibrosis. In the Asia-Pacific region, Thailand has the highest prevalence of systemic sclerosis, with an incidence of 24.4 per 100,000 population. Gastrointestinal involvement occurs in over 90% of patients with SScwith esophageal involvement being particularly common. Among these, gastroesophageal reflux disease (GERD) is present in approximately 80% of SSc patients. Erosive esophagitis (EE), a severe form of GERD characterized by the erosion of esophageal mucosa, is observed in about 80% of GERD cases. Its severity is classified according to the Los Angeles classification (grades A to D), with 30% of cases classified as severe (Los Angeles grades C and D). Proton pump inhibitors (PPIs) are currently the standard treatment for GERD and EE in SSc patients. However, fewer than 50% of patients demonstrate adequate response to PPIs therapy, highlighting the need for alternative treatments. Vonoprazan, a novel potassium-competitive acid blocker (PCAB), has emerged as a potent and longer-acting alternative to traditional PPIs. It has shown superior efficacy in treating severe erosive esophagitis in the general population. Previous cohort studies have demonstrated promising results with vonoprazan in improving symptoms and healing rates in SSc patients with refractory GERD up to 60% in refractory GERD; However, randomized controlled trials evaluating its efficacy in this population remain limited. This study aims to conduct a randomized controlled trial comparing the efficacy of vonoprazan and PPIs in treating erosive esophagitis in SSc patients.

Aims & Methods

The aim was to compare the efficacy of vonoprazan and lansoprazole in healing erosive esophagitis in patients with systemic sclerosis.
A randomized placebo-controlled trial was conducted in patients with systemic sclerosis (SSc) and refractory GERD who had erosive esophagitis confirmed by endoscopy. Participants were recruited from the systemic sclerosis clinic at Srinagarind Hospital, Khon Kaen University, from June 2024 to March 2025. Patients were randomized to receive either vonoprazan 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. The primary outcome was the percentage of healing at 8 weeks. Secondary outcomes included improvement in gastro-esophageal reflux disease (GERD) symptoms, as assessed by the Frequency Scale for the Symptoms of GERD (FSSG), GERD Questionnaire (GerdQ), and visual analogue scales (VAS) for heartburn and regurgitation.

Results

A total of 48 patients were enrolled in the study. The healing rates for vonoprazan and lansoprazole were 73.9% and 39.1%, respectively, resulting in an absolute risk reduction of 0.348 (95% CI: 0.081–0.614; p-value: 0.017). Subgroup analysis of patients with severe erosive esophagitis, defined as Los Angeles (LA) grades C-D, demonstrated that vonoprazan was superior to lansoprazole (75% vs. 33.3%; absolute risk reduction: 0.52; 95% CI: 0.167–0.873; p-value: 0.008). No significant difference was observed between the two treatments in patients with LA grades A-B.

Conclusion

Preliminary data suggests that vonoprazan was superior to lansoprazole in the healing of erosive esophagitis in systemic sclerosis patients, with this benefit being particularly evident in cases of severe erosive esophagitis (LA grades C-D).

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