Invited Editorials pressants,10 rather than the current ‘one size fits all’ PPIs, refractory oesophagitis may become a disease of the past.
ACKNOWLEDGEMENTS Declaration of personal interests: Carmelo Scarpignato has served as a speaker, consultant and/or advisory board member for Alfa Wassermann, AstraZeneca, Boeheringer-Ingelheim, Giuliani Pharmaceuticals, Pfizer, Recordati, Sigma-Tau, Shire and Warner-Chilcott, and has in the past received funding from Giuliani Pharmaceuticals and Pfizer. Declaration of funding interests: None. REFERENCES 1. Kahrilas PJ, Persson T, Denison H, Wernersson B, Hughes N, Howden CW. Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression. Aliment Pharmacol Ther 2014; 40: 648–56. 2. Hunt RH. Importance of pH control in the management of GERD. Arch Intern Med 1999; 159: 649–57.
Editorial: healing of refractory reflux oesophagitis – an ongoing unmet clinical need; authors’ reply P. J. Kahrilas*, T. Persson†, H. Denison†, B. Wernersson†, N. Hughes‡ & C. W. Howden* *Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. † AstraZeneca R&D, M€ olndal, Sweden. ‡ Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, UK. E-mail: [email protected] doi:10.1111/apt.12943
We thank Hunt et al. for their insights.1 Indeed, our findings highlight the complex relationship between reflux oesophagitis (RO) healing, symptoms and acid suppression, reinforcing earlier findings and suggesting that ‘RO’ in some patients may require more than 8 weeks treatment to achieve healing.2 In response to specific points raised: (i) We think that focusing on the proportion of patients with known regurgitation at baseline was appropriate, rather than pooling the small number of patients with missing regurgitation data with those who did not have the symptom. Although the latter approach would certainly be acceptable, we judged that this would yield an overly conservative result. (ii) Our regression model for group A included LA grade, sex, HH, heartburn, and (any frequency of) regurgitation at baseline. Aliment Pharmacol Ther 2014; 40: 982-989 ª 2014 John Wiley & Sons Ltd
3. Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112: 1798–810. 4. Yaghoobi M, Padol S, Yuan Y, Hunt RH. Impact of oesophagitis classification in evaluating healing of erosive oesophagitis after therapy with proton pump inhibitors: a pooled analysis. Eur J Gastroenterol Hepatol 2010; 22: 583–90. 5. Yuan Y, Hunt RH. Evolving issues in the management of reflux disease? Curr Opin Gastroenterol 2009; 25: 342–51. 6. Frazzoni M, De Micheli E, Grisendi A, Savarino V. Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression. Aliment Pharmacol Ther 2002; 16: 881–6. 7. Moayyedi P, Santana J, Khan M, Preston C, Donnellan C. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev 2007; 2: CD003244. 8. Yuan Y, Vinh B, Hunt RH. Non-healed rate of moderate-severe (LA classification grade C and D) erosive esophagitis after 4-8 weeks proton pump inhibitors (PPIs): evidence of an unmet need. Gastroenterology 2009; 136(Suppl. 1): A–440. 9. Hunt RH. Acid suppression for reflux disease: “off-the-peg” or a tailored approach? Clin Gastroenterol Hepatol 2012; 10: 210–3. 10. Scarpignato C, Hunt RH. Proton pump inhibitors: the beginning of the end or the end of the beginning? Curr Opin Pharmacol 2008; 8: 677–84.
(iii) Our sentence that ‘Week 4 possible predictors of refractory vs. slow healing RO were assessed’ refers to the presence or absence of symptoms after 4 weeks as predictors of 8-week healing in group B (4-week symptoms were not used in logistic regression). (iv) As we demonstrated, Hunt et al. are correct that a lower proportion of patients with refractory RO (51%) had HH than rapid (64%) or slow healers (69%). However, we maintain that the sample sizes for refractory RO (n = 49) and slow healers (n = 78) are small compared with that for rapid healing (n = 495). (v) We agree that overlapping confidence intervals do not preclude a significant difference and it is true that the statistical outcome is not necessarily a consequence of the sample sizes. Our aim here was merely to suggest that the smaller sample would be a factor in determining the confidence intervals.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Hunt RH, Yuan Y, Scarpignato C. Editorial: healing of refractory reflux esophagitis: an ongoing unmet clinical need. Aliment Pharmacol Ther 2014; 40: 987–9. 2. Kahrilas PJ, Persson T, Denison H, Wernersson B, Hughes N, Howden CW. Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression. Aliment Pharmacol Ther 2014; 40: 648–56. 989
ACKNOWLEDGEMENTS Declaration of personal interests: Carmelo Scarpignato has served as a speaker, consultant and/or advisory board member for Alfa Wassermann, AstraZeneca, Boeheringer-Ingelheim, Giuliani Pharmaceuticals, Pfizer, Recordati, Sigma-Tau, Shire and Warner-Chilcott, and has in the past received funding from Giuliani Pharmaceuticals and Pfizer. Declaration of funding interests: None. REFERENCES 1. Kahrilas PJ, Persson T, Denison H, Wernersson B, Hughes N, Howden CW. Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression. Aliment Pharmacol Ther 2014; 40: 648–56. 2. Hunt RH. Importance of pH control in the management of GERD. Arch Intern Med 1999; 159: 649–57.
Editorial: healing of refractory reflux oesophagitis – an ongoing unmet clinical need; authors’ reply P. J. Kahrilas*, T. Persson†, H. Denison†, B. Wernersson†, N. Hughes‡ & C. W. Howden* *Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. † AstraZeneca R&D, M€ olndal, Sweden. ‡ Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, UK. E-mail: [email protected] doi:10.1111/apt.12943
We thank Hunt et al. for their insights.1 Indeed, our findings highlight the complex relationship between reflux oesophagitis (RO) healing, symptoms and acid suppression, reinforcing earlier findings and suggesting that ‘RO’ in some patients may require more than 8 weeks treatment to achieve healing.2 In response to specific points raised: (i) We think that focusing on the proportion of patients with known regurgitation at baseline was appropriate, rather than pooling the small number of patients with missing regurgitation data with those who did not have the symptom. Although the latter approach would certainly be acceptable, we judged that this would yield an overly conservative result. (ii) Our regression model for group A included LA grade, sex, HH, heartburn, and (any frequency of) regurgitation at baseline. Aliment Pharmacol Ther 2014; 40: 982-989 ª 2014 John Wiley & Sons Ltd
3. Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112: 1798–810. 4. Yaghoobi M, Padol S, Yuan Y, Hunt RH. Impact of oesophagitis classification in evaluating healing of erosive oesophagitis after therapy with proton pump inhibitors: a pooled analysis. Eur J Gastroenterol Hepatol 2010; 22: 583–90. 5. Yuan Y, Hunt RH. Evolving issues in the management of reflux disease? Curr Opin Gastroenterol 2009; 25: 342–51. 6. Frazzoni M, De Micheli E, Grisendi A, Savarino V. Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression. Aliment Pharmacol Ther 2002; 16: 881–6. 7. Moayyedi P, Santana J, Khan M, Preston C, Donnellan C. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev 2007; 2: CD003244. 8. Yuan Y, Vinh B, Hunt RH. Non-healed rate of moderate-severe (LA classification grade C and D) erosive esophagitis after 4-8 weeks proton pump inhibitors (PPIs): evidence of an unmet need. Gastroenterology 2009; 136(Suppl. 1): A–440. 9. Hunt RH. Acid suppression for reflux disease: “off-the-peg” or a tailored approach? Clin Gastroenterol Hepatol 2012; 10: 210–3. 10. Scarpignato C, Hunt RH. Proton pump inhibitors: the beginning of the end or the end of the beginning? Curr Opin Pharmacol 2008; 8: 677–84.
(iii) Our sentence that ‘Week 4 possible predictors of refractory vs. slow healing RO were assessed’ refers to the presence or absence of symptoms after 4 weeks as predictors of 8-week healing in group B (4-week symptoms were not used in logistic regression). (iv) As we demonstrated, Hunt et al. are correct that a lower proportion of patients with refractory RO (51%) had HH than rapid (64%) or slow healers (69%). However, we maintain that the sample sizes for refractory RO (n = 49) and slow healers (n = 78) are small compared with that for rapid healing (n = 495). (v) We agree that overlapping confidence intervals do not preclude a significant difference and it is true that the statistical outcome is not necessarily a consequence of the sample sizes. Our aim here was merely to suggest that the smaller sample would be a factor in determining the confidence intervals.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Hunt RH, Yuan Y, Scarpignato C. Editorial: healing of refractory reflux esophagitis: an ongoing unmet clinical need. Aliment Pharmacol Ther 2014; 40: 987–9. 2. Kahrilas PJ, Persson T, Denison H, Wernersson B, Hughes N, Howden CW. Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression. Aliment Pharmacol Ther 2014; 40: 648–56. 989
