Marta Illueca

Efficacy and Safety of Once-Daily Esomeprazole for the Treatment of Gastroesophageal Reflux Disease in Neonatal Patients

OBJECTIVE To evaluate the efficacy and safety of proton pump inhibitors in infants aged <1 year with gastroesophageal reflux disease (GERD). STUDY DESIGN In this randomized, double-blind, placebo-controlled multicenter study, neonates (premature to 1 month corrected age; n = 52) with signs and symptoms of GERD received esomeprazole 0.5 mg/kg or placebo once daily for up to 14 days. Change from baseline in the total number of GERD symptoms (from video monitoring) and GERD-related signs (from cardiorespiratory monitoring) was assessed with simultaneous esophageal pH, impedance, cardiorespiratory, and 8-hour video monitoring. RESULTS There were no significant differences between the esomeprazole and placebo groups in the percentage change from baseline in the total number of GERD-related signs and symptoms (-14.7% vs -14.1%, respectively). Mean change from baseline in total number of reflux episodes was not significantly different between esomeprazole and placebo (-7.43 vs -0.2, respectively); however, the percentage of time pH was <4.0 and the number of acidic reflux episodes >5 minutes in duration was significantly decreased with esomeprazole vs placebo (-10.7 vs 2.2 and -5.5 vs 1.0, respectively; P ≤ .0017). The number of patients with adverse events was similar between treatment groups. CONCLUSIONS Signs and symptoms of GERD traditionally attributed to acidic reflux in neonates were not significantly altered by esomeprazole treatment. Esomeprazole was well tolerated and reduced esophageal acid exposure and the number of acidic reflux events in neonates.

Safety and symptom improvement with esomeprazole in adolescents with gastroesophageal reflux disease.

Objectives: The primary objective was to assess the safety of esomeprazole 20 or 40 mg once daily in adolescents with clinically diagnosed gastroesophageal reflux disease (GERD). A secondary aim was to assess changes in GERD symptoms after esomeprazole therapy. Patients and Methods: In this multicenter, randomized, double-blind study, adolescents ages 12 to 17 years inclusive received esomeprazole 20 or 40 mg once daily for 8 weeks. Adverse events and changes in clinical parameters (eg, physical examination, laboratory measurements) were evaluated to assess safety. Patients or their parents or guardians scored symptom severity daily, and investigators scored overall GERD symptom severity every 2 weeks using a 4-point scale. Results: In the 148 adolescents with safety data, treatment-related and non–treatment-related adverse events were reported by 75% and 78% of patients in the esomeprazole 20- and 40-mg groups, respectively. Twenty-two patients (14.9%) experienced adverse events that were considered related to treatment; the most common were headache (8%, 12/148), abdominal pain (3%, 4/148), nausea (2%, 3/148), and diarrhea (2%, 3/148). No serious adverse events or clinically important findings in other safety assessments were observed. At baseline, 68% (100/147) had heartburn, 63% (93/147) had epigastric pain, 57% (84/147) had acid regurgitation, and 15% (22/147) had vomiting symptoms. Symptom scores decreased significantly in both the esomeprazole 20-mg and 40-mg groups by the final study week (P < 0.0001). Investigators rated 63.1% (94/149) of the patients as having moderate or severe symptoms at baseline; at the final visit, this percentage decreased significantly to 9.3% (13/140; P < .0001). Conclusions: In adolescent patients with GERD, esomeprazole 20 or 40 mg daily for 8 weeks was well tolerated, and GERD-related symptoms were significantly reduced from baseline values in both groups.

Safety and Tolerability of Esomeprazole in Children With Gastroesophageal Reflux Disease.

Objectives: To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). Patients and Methods: In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physicians Global Assessment (PGA). Patients’ parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0–3) at baseline (based on past 72 hours) and daily (from past 24 hours). Results: Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) Conclusions: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.

Objectives: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. Methods: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5–10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5–10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. Results: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. Conclusions: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.OBJECTIVES Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.OBJECTIVES Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Pancreatitis after surgery in adolescent idiopathic scoliosis: incidence and risk factors.

Acute pancreatitis has been documented as a postoperative complication in both the general surgery and orthopaedic literature. The etiology of pancreatitis in the postoperative orthopaedic population is not clear. The purpose of this study was to determine the incidence and possible predisposing factors for acute pancreatitis after scoliosis surgery in adolescent patients. This is a retrospective review of records and radiographs of patients undergoing surgery for adolescent idiopathic scoliosis during a 3-year period from 1995 to 1997. Twelve of 80 patients reviewed had amylase and lipase blood levels analyzed because of abdominal symptoms. Twenty-two clinical and radiologic parameters were assessed in each patient. Seven patients (9%) had elevated serum lipase or amylase levels consistent with pancreatitis. The only statistically different parameters were age, height, body mass index, days of postoperative fasting, and hospital stay (pancreatitis patients were older and taller and had a lower body mass index, and their hospital stay was longer). Older age and lower body index mass were the only factors relating to postoperative pancreatitis.

Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study

BackgroundAcid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.MethodsChildren aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.ResultsOf 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.ConclusionsEsomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.Trial RegistrationD9614C00097; ClinicalTrials.gov identifier NCT00228527.

Maintenance treatment with proton pump inhibitors for reflux esophagitis in pediatric patients: a systematic literature analysis.

Objectives: Short-term treatment with a proton pump inhibitor (PPI) is effective for healing reflux esophagitis and improving reflux symptoms in pediatric patients. Our aim was to assess the efficacy and tolerability of maintenance PPI treatment after healing of reflux esophagitis in pediatric patients. Materials and Methods: Systematic searches of MEDLINE, Excerpta Medica database, and recent conference abstracts. Results: Five studies evaluated the efficacy of PPI maintenance therapy (6- to 90-month follow-up) in pediatric patients after healing of reflux esophagitis. Three found no relapse of reflux esophagitis or reflux symptoms during PPI maintenance therapy; however, a low relapse rate (1/14) was also found in the placebo group of the only prospective controlled study. Two of the 5 studies (both prospective) reported relapse of reflux esophagitis at half the original healing dose of omeprazole (7 of 51 patients relapsed after 3 months; 8 of 32 within 21 months), which resolved again in most patients when the healing dose or higher was given. Four studies evaluated relapse of reflux esophagitis and/or reflux symptoms after stopping PPI therapy. Reflux symptoms recurred in 18% to 76% of patients across all 4 studies. In the 4 studies that assessed the safety of PPI maintenance therapy, adverse events were infrequent and of low severity. Conclusions: Pediatric patients with gastroesophageal reflux disease and certain chronic comorbidities appear to have the greatest need of maintenance PPI treatment after healing of reflux esophagitis. In patients requiring maintenance therapy, PPIs appear to be well tolerated and effective in maintaining remission of reflux esophagitis and reflux symptoms.

Clinical trial: gastric acid suppression in Hispanic adults with symptomatic gastro‐oesophageal reflux disease – comparator study of esomeprazole, lansoprazole and pantoprazole

Aliment Pharmacol Ther 2010; 32: 200–208

Healing of Erosive Esophagitis and Improvement of Symptoms of Gastroesophageal Reflux Disease After Esomeprazole Treatment in Children 12 to 36 Months Old.

Objectives: The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD). Patients and Methods: Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment. Results: Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ⩽ 0.0018). Conclusions: Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year. Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.OBJECTIVES The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment. RESULTS Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018). CONCLUSIONS Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year.Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.OBJECTIVES The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment. RESULTS Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018). CONCLUSIONS Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year. Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.

Review of the persistence of gastroesophageal reflux disease in children, adolescents and adults: does gastroesophageal reflux disease in adults sometimes begin in childhood?

Abstract Objective. Understanding the natural history and outcomes of gastroesophageal reflux disease (GERD) in children could help to identify patients at risk of having GERD complications during adulthood. This review aimed to assess evidence of whether GERD in children or adolescents persists into adulthood. Material and methods. PubMed searches (1966–2010) identified longitudinal studies of GERD extending from childhood/infancy into adulthood, as well as longitudinal studies within pediatric age groups. Results. In one study, heartburn during childhood was more often recalled by adults with reflux symptoms than by those without (30% vs. 9%; p < 0.001), as was medication or surgery for GERD (both p < 0.01). Another study found that GERD symptoms were more common in adults diagnosed with reflux esophagitis during childhood/adolescence than in those who were not (46% vs. 30%). Regurgitation during infancy increased the risk of feeding problems after 1 year (odds ratio 4.2 (95% confidence interval: 1.4–12.0)) and of reflux symptoms at 9 years of age (relative risk 2.3 (95% confidence interval: 1.3–4.0)). In one study, abnormal esophageal histology persisted in infants after 12 months without reflux symptoms. A proportion (59–100%: three studies) of patients with reflux symptoms and/or reflux esophagitis during the pediatric years still required treatment after 1–8 years. In another study, however, just 7% of patients with healed reflux esophagitis relapsed after 9 months without treatment. Conclusion. The limited available evidence suggests that some infants, children, and adolescents with GERD are more likely than those without GERD to have symptoms later in life.