Review question
Are antibiotics useful for the treatment of peptic ulcer (ulcers in the stomach or upper small intestine) in people with Helicobacter pylori (H. pylori) infection?
Background
Peptic ulcers are caused by acidic stomach juices damaging the lining of the stomach (gastric ulcer) or upper small intestine (duodenal ulcer). This causes pain, indigestion and sometimes, bleeding. Ulcers can return after being healed, especially if the person is infected with Helicobacter pylori (a lifelong infection unless treated). H. pylori causes most peptic ulcers. It is not clear whether eradicating H.pylori by treating with antibiotics as part of a combination of drugs (H.pylori eradication therapy) is helpful in the treatment of people with peptic ulcers compared to no treatment or other medical treatments. This is an update of a previous Cochrane review published in 2006.
Study characteristics
Fifty-five studies provided information for the review. Thirty-four studies compared H. pylori eradication therapy plus ulcer-healing drug against ulcer-healing drug alone in the healing of duodenal ulcer. Two studies compared H. pylori eradication therapy against no treatment in the healing of duodenal ulcer. Fifteen studies compared H. pylori eradication therapy plus ulcer-healing drug against ulcer-healing drug alone in the healing of gastric ulcer. Three studies compared H. pylori eradication therapy plus ulcer-healing drug against ulcer-healing drug alone in the healing of peptic ulcer (gastric or duodenal ulcer). One study compared H. pylori eradication therapy against no treatment in the healing of peptic ulcer (gastric or duodenal ulcer). Four studies compared H. pylori eradication therapy against ulcer-healing drug in preventing the recurrence of duodenal ulcer after initial ulcer had been healed. Twenty-seven studies compared H. pylori eradication therapy against no treatment in preventing the recurrence of duodenal ulcer after initial ulcer had been healed. Twelve studies compared H. pylori eradication therapy against no treatment in preventing the recurrence of gastric ulcer after initial ulcer had been healed, while one study compared H. pylori eradication therapy against no treatment in preventing the recurrence of peptic ulcer (gastric or duodenal ulcer) after initial ulcer had been healed. Four studies compared H. pylori eradication therapy plus ulcer-healing drug versus comparison regimen in the relief of symptoms from peptic ulcer (gastric or duodenal ulcer). There were no studies comparing H. pylori eradication therapy against no treatment in the healing of gastric ulcer, H. pylori eradication therapy against ulcer-healing drug as maintenance therapy in preventing the recurrence of gastric ulcer after initial ulcer had been healed, or H. pylori eradication therapy plus ulcer-healing drug against no treatment or ulcer-healing drug in the relief of symptoms in people with peptic ulcer. Some trials provided information for more than one comparison. The evidence is current until March 2016.
Key results
Adding a one to two-week course of H. pylori eradication therapy speeds up ulcer healing for people with H. pylori-positive duodenal ulcer when compared to ulcer-healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer (ulcer returning after initial healing) compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer-healing drugs. However, because of the small number of studies included for the last two comparisons, significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.
Quality of the evidence
The quality of evidence was low or very low because most of the studies had errors in study design. As a result, there is a lot of uncertainty regarding the results.
Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.
Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4.
To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.
To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.
To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.
To assess the proportion of participants in whom successful eradication was achieved.
In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials.
We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards.
We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible.
A total of 55 trials were included for one or more outcomes for this review.
In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).
In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).
In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy.