Real‐World Effectiveness and Safety of <i>Saccharomyces boulardii</i> <scp>CNCM</scp> I‐745 as Adjunct Therapy for <scp> <i>Helicobacter pylori</i> </scp> Eradication: Data From the European Registry on <scp> <i>H. pylori</i> </scp> Management (Hp‐ <scp>EuReg</scp> )

ABSTRACT Background Saccharomyces boulardii CNCM I‐745 (Sb) is one of the most widely used probiotics in clinical practice. The aim of this study was to assess the impact of adding Sb to Helicobacter pylori eradication therapy on treatment outcomes (effectiveness and safety) in routine European gastroenterology clinical practice. Materials and Methods Treatment‐naive cases from the European registry on H. pylori management (Hp‐EuReg) collected from 2013 to 2023 at AEG‐REDCap were analyzed. Effectiveness was assessed by modified intention‐to‐treat, by treatment and geographic regions. Multivariate analysis identified factors independently associated with eradication success and adverse event incidence. Results Among 69,922 cases, probiotics were used in 16,528 (24%) treatments, of which 4404 (27%) included Sb. Sb use was significantly associated with an increase in effectiveness (OR = 2.32; 95% confidence interval, 1.38–4.03; p &lt; 0.01) only when prescribed with concomitant therapy encompassing a proton pump inhibitor plus clarithromycin‐amoxicillin‐metronidazole. In addition, a significant reduction in the overall incidence of at least one adverse event was observed in the Sb group (OR = 0.803; 0.66–0.97; p &lt; 0.05). Specifically, diarrhea, nausea, dyspepsia, abdominal pain, asthenia, anorexia, heartburn, and dysgeusia occurred significantly less frequently with Sb. Treatment compliance was high in both groups (with and without Sb). Conclusions In Europe, the addition of Sb to first‐line regimens in clinical practice was associated with higher effectiveness when combined with concomitant therapy with clarithromycin‐amoxicillin‐metronidazole and with fewer overall adverse events, supporting its role as a beneficial adjunct in H. pylori eradication therapy. Registration Number ClinicalTrials.gov identifier: NCT02328131