Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people

  • Conclusions changed
  • Review
  • Intervention

Authors


Abstract

Background

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.

Objectives

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.

Search methods

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Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials.

Selection criteria

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.

Data collection and analysis

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.

Main results

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.

Authors' conclusions

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.

Plain language summary

Antibiotics for people with peptic ulcers caused by Helicobacter pylori infection

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.

Laički sažetak

Antibiotici kod pacijenata s peptičkim ulkusima uzrokovanima infekcijom s Helicobacter pylori bakterijom

Istraživačko pitanje

Jesu li antibiotici djelotvorni za liječenje peptičkih ulkusa (čirevi želuca i dvanaesnika, gornjeg dijela tankog crijeva) kod pacijenata s Helicobacter pylori (H. pylori) infekcijom?

Dosadašnje spoznaje

Peptički ulkusi uzrokovani su kiselim želučanim sokovima koji oštećuju sluznicu želuca (čir na želucu) ili dvanaesnika, gornjeg dijela tankog crijeva (čir na dvanaesniku). To uzrokuje bolove, otežanu probavu i ponekad, krvarenje. Ulkusi se mogu ponovno javiti nakon što su izliječeni ukoliko je osoba inficirana s bakterijom Helicobacter pylori (ukoliko se ne liječi, doživotna infekcija). H. pylori uzrokuje najviše peptičkih ulkusa. Nije jasno je li eradikacija H. pylori primjenom antibiotika kao dio kombinacije lijekova (eradikacijska terapija za H. pylori ) korisna u liječenju osoba s peptičkim ulkusima, u usporedbi s osobama koje nisu liječene nikakvom terapijom ili su primale drugo liječenje. Ovo je obnovljena verzija prethodnog Cochrane pregleda objavljenog 2006.

Obilježja studija

Podaci za ovaj Cochrane sustavni pregled dobiveni su iz 55 studija. Trideset i četiri studije upoređivale su eradikacijsku terapiju za H. pylori u kombinaciji s lijekovima za cijeljenje ulkusa naspram samostalne terapije lijekovima za cijeljenje ulkusa, u cijeljenju čira na dvanaesniku. Dvije su studije uspoređivale eradikacijsku terapiju za H. pylori naspram nikakve terapije, u cijeljenju čira na dvanaesniku. Petnaest je studija uspoređivalo eradikacijsku terapiju za H. pylori u kombinaciji s lijekovima za cijeljenje ulkusa naspram samostalne terapije lijekovima za cijeljenje ulkusa, u cijeljenju čira na želucu. Tri su studije uspoređivale eradikacijsku terapiju za H. pylori u kombinaciji s lijekovima za cijeljenje ulkusa naspram samostalne terapije lijekovima za cijeljenje ulkusa, u cijeljenju peptičkog ulkusa (čir na želucu ili dvanaesniku). Jedna je studija uspoređivala eradikacijsku terapiju za H. pylori naspram nikakve terapije, u cijeljenju peptičkog ulkusa (čir na želucu ili dvanaesniku). Četiri studije su uspoređivale eradikacijsku terapiju za H. pylori naspram lijekova za cijeljenje ulkusa, u prevenciji ponovne pojave čira na dvanaesniku nakon što je prvobitni čir zacijelio. Dvadeset sedam studija uspoređivalo je eradikacijsku terapiju za H. pylori naspram nikakve terapije u prevenciji ponovne pojave čira na dvanaesniku nakon što je prvobitni čir zacijelio. Dvanaest je studija uspoređivalo eradikacijsku terapiju za H. pylori naspram nikakve terapije za prevenciju ponovne pojave čira na želucu nakon što je prvobitni čir zacijelio, dok je jedna studija uspoređivala eradikacijsku terapiju za H. pylori naspram nikakve terapije u prevenciji ponovne pojave peptičkog ulkusa (čir na želucu ili dvanaesniku) nakon što je prvobitni čir zacijelio. Četiri su studije uspoređivale eradikacijsku terapiju za H. pylori u kombinaciji s lijekovima za cijeljenje ulkusa naspram kombinacije lijekova za smanjenje simptoma peptičkog ulkusa (čir na želucu ili dvanaesniku). Niti jedna studija nije uspoređivala eradikacijsku terapiju za H. pylori naspram nikakve terapije u cijeljenju čira na želucu, eradikacijsku terapiju za H. pylori naspram lijekova za cijeljenje ulkusa u terapiji održavanja za prevenciju ponovne pojave čira na želucu nakon što je prvobitni čir zacijelio ili eradikacijsku terapiju za H. pylori naspram nikakve terapije ili lijekova za cijeljenje ulkusa za smanjenje simptoma kod bolesnika s peptičkim ulkusom. Neke su studije dale informacije za više od jedne usporedbe. Obuhvaćena su sva istraživanja dostupna do ožujka 2016.

Ključni rezultati

Dodavanje eradikacijske terapije za H. pylori u trajanju od jednog do dva tjedna ubrzava cijeljenje ulkusa kod osoba s čirom na dvanaesniku pozitivnih na H. pylori naspram samostalne primjene lijekova za cijeljenje ulkusa i nikakve terapije. Eradikacijska terapija za H. pylori je također djelotvorna za ponovnu pojavu čira na želucu i dvanaesniku (nakon prethodnog cijeljenja ulkusa) naspram nikakve terapije.Trenutno nema dokaza da je eradikacijska terapija za H. pylori djelotvorno liječenje za osobe sa čirom na želucu ili da je djelotvorna za prevenciju ponovne pojave čira na dvanaesniku u usporedbi s lijekovima za cijeljenje ulkusa. Međutim, s obzirom da je za dvije posljednje usporedbe uključen mali broj studija, značajna korist ili šteta od eradikacijske terapije za H. pylori u akutnom cijeljenju čira na želucu naspram nikakve terapije te za prevenciju ponovne pojave čira na dvanaesniku naspram lijekova za cijeljenje ulkusa ne može se isključiti.

Kvaliteta dokaza

Kvaliteta dokaza je bila slaba ili vrlo slaba zbog toga što je većina studija imala greške u svom dizajnu. Stoga se u te rezultate ne možemo mnogo pouzdati.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Suzana Mimica Matanović
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr