REVISIÓN DE REVISTAS

Budesonide for Eosinophilic Esophagitis

Although the prevalence and awareness of eosinophilic esophagitis (EoE) in adults continue to increase, optimal treatment strategies remain undefined. Standard recommended therapy includes systemic or topical steroids (e.g., fluticasone). Recently, the use of budesonide has been reported as highly effective in pediatric patients (JW Gastroenterol Sep 24 2010), but its efficacy in adolescent and adult patients is unknown.

To investigate this issue, researchers randomized 36 patients aged 14 years with EoE to receive either 2 mg of budesonide (0.25 mg/mL) suspension or a placebo of saline solution in an industry-supported, doubleblind trial. Participants self-administered 4 mL of liquid via nebulizer into the oropharynx, followed by continuous swallowing for 10 minutes, twice daily for 15 days. Proton-pump inhibitors were allowed, but additional types of EoE therapy were discontinued.

Among the budesonide group, esophageal eosinophil load and self-reported dysphagia symptoms decreased from baseline to 15 days (P<0.0001 for both comparisons), as did production of proinflammatory cytokines, cell death, and fibrosis scores.

The placebo group experienced no significant changes in these outcomes. Complete histologic remission occurred in 72.2% of the treatment group but in only 11.1% of the placebo group (P<0.0001); among the 13 budesonide-treated patients who achieved remission, endoscopic improvement was evident in the disappearance of almost all white exudates and red furrows identified at baseline. In contrast, corrugated rings persisted in all but one patient. No serious adverse effects occurred; however, 3 of 18 patients in the budesonide group developed clinically asymptomatic esophageal infections with Candida albicans. Straumann A et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology 2010 Nov; 139:1526.

Are Proton-Pump Inhibitors Safe During Early Pregnancy?

Symptomatic gastroesophageal reflux disease (GERD) is a common condition associated with pregnancy. Although its prevalence increases with duration of pregnancy, symptoms often occur even in the first trimester. Proton-pump inhibitors (PPIs) are the most effective medical therapy for patients with moderate-to-severe GERD and are widely prescribed to pregnant women. However, safety data about the use of these agents during pregnancy or immediately prior to conception are limited (JW Gastroenterol Mar 29 2005).

To evaluate the association between exposure to PPIs and the risk for birth defects, researchers conducted a retrospective cohort study of live births in Denmark using multiple national registries. The primary analysis assessed PPI exposure to women during the 4 weeks prior to conception through the first trimester of pregnancy (12 weeks). The primary outcome measure was all major birth defects. Of 840,968 live births, 5082 involved exposure to PPIs during the study period. Exposure was associated with increased risk for birth defects (adjusted prevalence odds ratio, 1.23; 95% confidence interval, 1.05-1.44).

However, when exposure was limited to the first trimester only, no significant risk for birth defects remained. In a secondary analysis, exposures to specific PPIs during the first trimester did not increase the risk for birth defects. Of note, omeprazole - the only category C drug (i.e., animal studies have shown risk to a fetus) - was associated with the lowest risk for birth defects, although this result was not statistically significant. Pasternak B and Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med 2010 Nov 25; 363:2114.

Is Endoscopy Safe for Pregnant Women with Upper Gastrointestinal Bleeding?

Endoscopy is indicated for the diagnosis and treatment of nonvariceal upper gastrointestinal bleeding (UGIB). However, for pregnant women, the procedure is restricted to those with persistent or severe UGIB because of possible adverse effects on the mother and fetus. To estimate the rates of endoscopy and related adverse outcomes in pregnant women hospitalized with UGIB, investigators conducted a population- based, retrospective, cohort study involving 1210 pregnant patients identified from the U.S. Nationwide Inpatient Sample (NIS) from 1998 to 2007. Each patient was age-matched with five nonpregnant women controls admitted with UGIB. Pregnant patients were less likely to undergo endoscopy than nonpregnant controls (26% vs. 69%; P<0.0001; adjusted odds ratio, 0.19; 95% confidence interval, 0.16-0.22) and were less likely to undergo endoscopy within 24 hours of admission (50% vs. 57%; P=0.02).

The most common causes for UGIB were a Mallory-Weiss tear or an unspecified hematemesis among pregnant women and a peptic ulcer or gastritis among controls. In pregnant patients, rates of fetal and maternal complications were similar between those who underwent endoscopy and those who did not. In addition, rates of maternal mortality, fetal loss, fetal complications, or premature delivery were similar or lower among pregnant patients with UGIB than among a random sample of women in the NIS database who were hospitalized for obstetric causes. Nguyen GC et al. Endoscopic management and outcomes of pregnant women hospitalized for nonvariceal upper GI bleeding: A nationwide analysis. Gastrointest Endosc 2010 Nov; 72:954.

An Antibiotic for Irritable Bowel Syndrome?

Antibiotic use has been suggested to treat patients with irritable bowel syndrome (IBS), particularly for cases that are difficult to treat or are accompanied by bloating. One antibiotic that has shown efficacy in small IBS studies is rifaximin (JW Gastroenterol Oct 16 2006), a minimally absorbed, oral agent that has activity against gram-positive and gramnegative bacteria, anaerobes, and Clostridium difficile and is indicated for Escherichia coli-related travelers’ diarrhea and reduction of risk for hepatic encephalopathy.

To further test whether rifaximin can relieve IBS symptoms, investigators conducted two industry-supported, identically designed, double-blind, randomized, placebo-controlled trials involving a total of 1260 patients who had IBS without constipation. Patients received either rifaximin (550 mg 3 times daily) or placebo for 2 weeks and were followed for an additional 10 weeks. The primary endpoint was adequate relief of global IBS symptoms (patient-reported relief of symptoms for at least 2 of the first 4 weeks after initiation of treatment).

A secondary endpoint was adequate relief of IBS-related bloating. In the two studies combined, a higher proportion of participants in the rifaximin groups than in the placebo groups experienced adequate relief of global IBS symptoms (40.7% vs. 31.7%; P<0.001) and adequate relief of bloating (40.2% vs. 30.3%; P<0.001). Similar therapeutic gains were achieved in reducing IBS-related abdominal pain and loose or watery stools. Responses to rifaximin were sustained throughout follow-up for adequate relief of both global IBS symptoms and IBS-related bloating. Pimentel M et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011 Jan 6; 364:22.