University of Tennessee College of Medicine White, TN, United States
Colin Howden, MD, FACG1, Kely L. Sheldon, PhD2, June S. Almenoff, MD, PhD2, William D. Chey, MD, FACG3 1University of Tennessee College of Medicine, Germantown, TN; 2RedHill Biopharma, Raleigh, NC; 3Michigan Bowel Control Program, University of Michigan, Ann Arbor, MI
Introduction: H. pylori infects ~35% of Americans and can lead to serious sequalae if untreated. Clarithromycin (CLR)-based therapies have become increasingly ineffective at eradicating H. pylori due to increased antibiotic resistance. Despite guidance from the ACG which recommends avoiding CLR in patients who have previously received macrolides, and where local resistance rates are >15% or unknown, CLR is still frequently prescribed. Efficacy of CLR is strongly dependent on acid suppression by PPIs, which is reduced in individuals who are CYPC219 rapid/ultrarapid metabolizers (~30% prevalence). This study aimed to assess the impact of CYP2C19 genotype on eradication rates with physician-directed (PD) therapy with CLR, and to understand contemporary utilization of CLR in the US.
Methods: Clinical data from two phase 3 clinical trials (NCT03198507/NCT01980095) for RHB-105 were reviewed to identify specific PD regimens selected for subjects whose H. pylori infection was not eradicated during primary treatment. CYP2C19 metabolizer status was analyzed using genotyping in subjects who then received a PD CLR regimen. Additionally, an analysis of patient-level prescription claims (IQVIA) was performed to characterize real-world utilization of CLR.
Results: After study NCT03198507, CLR-triple was prescribed for 87% (27/31) of subjects with a cure rate of 59.3%. Following study NCT01980095, CLR-triple was prescribed for 51% (48/94) of subjects with a cure rate of 60.4%. Rapid CYP2C19 metabolizers who received CLR-regimens achieved an eradiation rate of 18.2% (2/11; pooled analysis). Real-world prescribing data revealed that over 80% of all H. pylori prescriptions contained CLR (Figure 1).
Discussion: Despite sub-optimal eradication rates and ACG recommendations, inappropriate use of CLR persists. PD therapy data confirmed high utilization of CLR with low rates of eradication. Rapid CYP2C19 metabolizers who received PD CLR-regimens had markedly low eradication rates, highlighting an additional concern complicating empirically prescribed CLR-based regimens. US prescription data confirm that CLR-based regimens predominate, despite recent guideline recommendations. Since RHB-105 does not contain CLR, and since resistance to amoxicillin and rifabutin is very rare, it can be used first-line without concern for antibiotic resistance or CYP2C19 genotype.
Figure: Figure 1: Percent of Total Prescribed H. pylori Regimens Containing Clarithromycin by Subspecialty
William Chey: AbbVie – Consultant. Alfasigma – Consultant. Alnylam – Consultant. Bayer – Consultant. Biomerica – Consultant, Grant/Research Support. Commonwealth Diagnostics International – Grant/Research Support. Cosmo – Consultant. GI on Demand – Stockholder/Ownership Interest (excluding diversified mutual funds). IM Health – Consultant. Ironwood – Consultant. Modify Health – Stockholder/Ownership Interest (excluding diversified mutual funds). Phathom Pharmaceuticals – Consultant. QOL Medical – Consultant, Grant/Research Support. RedHill Biopharma – Consultant. Salix/Valeant – Consultant, Grant/Research Support. Takeda – Consultant. Urovant – Consultant. Vibrant – Consultant.
Colin Howden, MD, FACG1, Kely L. Sheldon, PhD2, June S. Almenoff, MD, PhD2, William D. Chey, MD, FACG3. P3083 - Pitfalls of Physician-Directed Treatment of H. pylori Infection: Results From Two Phase 3 Clinical Trials and Real-World Prescribing Data, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.