Ignasi Puig1, Mireia Baylina2, Jordi Sánchez-Delgado3, Sheila López-Gongora2, David Suarez4, Pilar García-Iglesias5, Neus Muñoz6, Javier P Gisbert7, Cristina Dacoll8, Henry Cohen8, Xavier Calvet9. 1. Digestive Diseases Unit, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Spain Universitat Internacional de Catalunya, Barcelona, Spain Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. 2. Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain. 3. Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 4. Unitat d'Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain. 5. Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain. 6. Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain. 7. Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain. 8. Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 9. Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain xcalvet@tauli.cat.
Abstract
BACKGROUND: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies. OBJECTIVES: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis. METHODS: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates. RESULTS: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies. CONCLUSIONS: PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.
BACKGROUND: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies. OBJECTIVES: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis. METHODS: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates. RESULTS: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies. CONCLUSIONS:PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.