Evolution of Gastro-oesophageal Reflux Disease Over 5 Years Under Routine Medical Care

The ProGERD Study

P. Malfertheiner; M. Nocon; M. Vieth; M. Stolte; D. Jaspersen; H. R. Koelz; J. Labenz; A. Leodolter; T. Lind; K. Richter; S. N. Willich


Aliment Pharmacol Ther. 2012;35(1):154-164. 

In This Article



A total of 6215 patients were enrolled in the original study of whom 2721 attended follow-up at 5 years and had upper GI endoscopy. The baseline characteristics for the 2721 patients are summarised in Table 1, by GERD category at entry (Appendix S1). They compared well with the characteristics of the dropouts, suggesting that the population sample that completed the study remained consistent. The mean ages for each category were similar, but the proportions of males and of smokers increased with increasing severity of GERD, as did the duration of the disease. Familial history of GERD was slightly more common in those with more severe GERD, and generally, they had a lower prevalence of H. pylori infection. Of the patients, 240 were classified as having either endoscopic (n = 115) or confirmed Barrett's oesophagus (n = 125) at baseline. Their baseline characteristics were most similar to the patient group with LA grade C/D oesophagitis, in whom Barrett's oesophagus was most common (Barrett's was present in 2.5% of NERD, 10.8% of LA grade A/B and 28.1% of LA grade C/D patients). These patients were not included in the analysis of GERD progression.

Initial Treatment Phase

Healing rates following initial treatment with esomeprazole are presented in Table 1. 'Symptomatic' healing was reported for 88% of NERD patients, while ERD healing declined from 92% in milder oesophagitis LA grade A/B to 84% in LA grade C/D patients and to 74% in patients with Barrett's oesophagus at baseline.

Progression of GERD Severity

Progression, regression or stability of GERD categories between grades at both 2 years and 5 years are summarised in Table 2a. Most patients remained stable or showed improvement in their grade of oesophagitis. However, some patients with milder oesophagitis did progress to more severe grades C/D and also to Barrett's oesophagus. A multivariate analysis of baseline factors that may be associated with GERD progression to LA grade A/B or C/D after 5 years (Table 2b) indicated that a family history of GERD was associated with progression, and that remaining unhealed after baseline treatment predisposed patients to progression. Regular intake of PPI reduced the likelihood of progression compared with on-demand PPI or other therapy, although the severity of symptoms at baseline did not seem to be a predictor of progression (Table 2b).


When reflux symptoms (recorded in the RDQ) were compared at each time point between patients who progressed in GERD severity and those who did not (Figure 1a), there were no significant differences (with the exception of year 1, where symptoms were slightly worse in the group who progressed in severity, P = 0.018). Similarly, no significant differences in epigastric pain levels were noted between patients who progressed in GERD severity and those who did not (Figure 1b).

Figure 1.

(a) Mean reflux symptom scores throughout the study in patients with and without progression of GERD severity. Difference in year 1 significant (P = 0.018), all other years no significant differences between progression/no progression. (b) Mean epigastric pain scores throughout the study in patients with and without progression of GERD severity. No significant differences between progression/no progression.

Progression of Barrett's Oesophagus

At 5 years, 5.9% of the NERD patients, 12.1% of the LA grade A/B patients and 19.7% of the LA grade C/D patients in whom no Barrett's oesophagus was recorded at baseline, had endoscopic or confirmed Barrett's oesophagus (Table 3a). Of the 241 patients who progressed to endoscopic or confirmed BE at 5 years, data on length of the BE segment were available for 186 cases, and in 73% of them, the length was ≤2 cm (79% for NERD, 73% for LA grade A/B and 66% for LA grade C/D). Patients were assigned the diagnosis of 'confirmed' Barrett's oesophagus only if intestinal metaplasia was present in biopsies. In some patients with endoscopic signs, and particularly in short segment cases, only gastric metaplasia was reported. These patients are included under the 'endoscopic' category. Gastric metaplasia was present in 50% of patients with BE length ≤1 cm and in 29% with BE length >1–<3 cm. In patients with a BE length of 3 cm or more, no gastric metaplasia was observed. Proportions of gastric and intestinal metaplasia recorded for the different lengths of columnar epithelium are presented in Figure 2. The total proportion of patients who progressed from NERD, LA grade A/B or LA grade C/D to endoscopic or confirmed Barrett's oesophagus at 5 years was 9.7% (n = 241).

Figure 2.

Gastric and intestinal metaplasia (%) found in confirmed Barrett's columnar epithelium.

The factors selected for assessment of their influence on progression to Barrett's oesophagus are summarised in Table 3b. A multivariate analysis revealed that the presence of oesophagitis at baseline was the most significant factor associated with progression to Barrett's oesophagus. Other significant factors were the intake of alcohol or PPI, especially regular intake.