Letters to the Editors
Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet – authors’ reply K. Kaukinen* & P. S. Daugherty† *Department of Gastroenterology and Alimentary Tract Surgery, Univeristy of Tampere, Tampere, Finland. † Department of Chemical Engineering, University of California, Santa Barbara, CA, USA. E-mail: [email protected] doi:10.1111/apt.12729
SIRS, We thank Professor Matuchansky for his comments concerning our manuscript.1, 2 Continued gluten ingestion is surely the leading cause of nonresponsive coeliac disease. Similar to our patient series, some patients suffering from type 1 or 2 refractory coeliac disease have been reported to have low positive serum transglutaminase 2-antibody levels, despite a strict gluten-free diet.2–5 This might be considered as a sign of ongoing gluten ingestion and one could argue that these patients have been mis-classified as having truly nonresponsive condition. Due to the lack of reliable tools it is often challenging to uncover minor dietary lapses or inadvertent gluten intake. In Finland, there is a high prevalence of clinically diagnosed coeliac disease, and the majority (approximately 90%) of the patients adhere to a strict gluten-free diet. On a long-term gluten-free diet intestinal mucosa recovers in 96% of coeliac patients, and the prevalence of refractory coeliac disease is rare in Finland.6 In the current study,2 nonresponsive coeliac disease patients were from this well-defined patient cohort. The patients here had been followed up for a median of 10 years (up to 30 years) meaning that dietary adherence had been rigorously assessed not only once but several times over the years. In addition to 4-day food records, the
Letter: biological drugs for inducing remission in ulcerative colitis D. Maratea*, V. Fadda*, S. Trippoli*, R. Gatto*, M. De Rosa†, C. Marinai‡ & A. Messori* *HTA Unit, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. † SIFACT, Italian Society for Clinical Pharmacy and Therapeutics, Milan, Italy. ‡ Department of Pharmaceutical Logistics, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. E-mail: [email protected] doi:10.1111/apt.12690 1242
patients had been interviewed repeatedly by a trained dietitian and coeliac disease experts to uncover hidden gluten traces. Based on these assessments, the strictness of the gluten-free diets of nonresponsive cases was equivalent to that of responsive cases. Finally, regardless of the impact of trace gluten ingestion, the anti-deamidated gliadin peptide assays described were able to distinguish histologically nonresponsive patients from histologically responsive patients with high accuracy. With regard to the second point, we have applied the definition of latent refractory coeliac disease as previously introduced,5 wherein symptoms are required for a diagnosis of refractory coeliac disease, and did not manifest in the latent group until sometime after blood was collected.
ACKNOWLEDGEMENTS The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Matuchansky C. Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet. Aliment Pharmacol Ther 2014; 39: 1241. 2. Spatola BN, Kaukinen K, Collin P, Mäki M, Kagnoff MF, Daugherty PS. Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease. Aliment Pharmacol Ther 2014; 39: 407–17. 3. Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology 2009; 136: 99–107. 4. Roshan B, Leffler DA, Jamma S, et al. The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol 2011; 106: 923–8. 5. Kaukinen K, Peräaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25: 1237–45. 6. Ilus T, Kaukinen K, Virta LJ, et al. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther 2014; 39: 418–25.
SIRS, When nonsignificant results are found in trials or meta-analyses, differentiating between no proof of difference (an ‘inconclusive’ result)1 and proof of no difference (equivalence, a ‘conclusive’ result)1 is increasingly recognised to be a crucial step for a correct interpretation.2–4 We have reanalysed the trials examined by Stidham and co-workers5 for the end-point of induction of remission. Firstly, the meta-analysis results were re-expressed using risk difference (RD) rather than relative risk.6 Then, the pooled RDs for direct comparisons of biologics vs placebo were subjected to network meta-analysis. In this way, the pooled values of RD were estimated for the Aliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet – authors’ reply K. Kaukinen* & P. S. Daugherty† *Department of Gastroenterology and Alimentary Tract Surgery, Univeristy of Tampere, Tampere, Finland. † Department of Chemical Engineering, University of California, Santa Barbara, CA, USA. E-mail: [email protected] doi:10.1111/apt.12729
SIRS, We thank Professor Matuchansky for his comments concerning our manuscript.1, 2 Continued gluten ingestion is surely the leading cause of nonresponsive coeliac disease. Similar to our patient series, some patients suffering from type 1 or 2 refractory coeliac disease have been reported to have low positive serum transglutaminase 2-antibody levels, despite a strict gluten-free diet.2–5 This might be considered as a sign of ongoing gluten ingestion and one could argue that these patients have been mis-classified as having truly nonresponsive condition. Due to the lack of reliable tools it is often challenging to uncover minor dietary lapses or inadvertent gluten intake. In Finland, there is a high prevalence of clinically diagnosed coeliac disease, and the majority (approximately 90%) of the patients adhere to a strict gluten-free diet. On a long-term gluten-free diet intestinal mucosa recovers in 96% of coeliac patients, and the prevalence of refractory coeliac disease is rare in Finland.6 In the current study,2 nonresponsive coeliac disease patients were from this well-defined patient cohort. The patients here had been followed up for a median of 10 years (up to 30 years) meaning that dietary adherence had been rigorously assessed not only once but several times over the years. In addition to 4-day food records, the
Letter: biological drugs for inducing remission in ulcerative colitis D. Maratea*, V. Fadda*, S. Trippoli*, R. Gatto*, M. De Rosa†, C. Marinai‡ & A. Messori* *HTA Unit, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. † SIFACT, Italian Society for Clinical Pharmacy and Therapeutics, Milan, Italy. ‡ Department of Pharmaceutical Logistics, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. E-mail: [email protected] doi:10.1111/apt.12690 1242
patients had been interviewed repeatedly by a trained dietitian and coeliac disease experts to uncover hidden gluten traces. Based on these assessments, the strictness of the gluten-free diets of nonresponsive cases was equivalent to that of responsive cases. Finally, regardless of the impact of trace gluten ingestion, the anti-deamidated gliadin peptide assays described were able to distinguish histologically nonresponsive patients from histologically responsive patients with high accuracy. With regard to the second point, we have applied the definition of latent refractory coeliac disease as previously introduced,5 wherein symptoms are required for a diagnosis of refractory coeliac disease, and did not manifest in the latent group until sometime after blood was collected.
ACKNOWLEDGEMENTS The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Matuchansky C. Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet. Aliment Pharmacol Ther 2014; 39: 1241. 2. Spatola BN, Kaukinen K, Collin P, Mäki M, Kagnoff MF, Daugherty PS. Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease. Aliment Pharmacol Ther 2014; 39: 407–17. 3. Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology 2009; 136: 99–107. 4. Roshan B, Leffler DA, Jamma S, et al. The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol 2011; 106: 923–8. 5. Kaukinen K, Peräaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25: 1237–45. 6. Ilus T, Kaukinen K, Virta LJ, et al. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther 2014; 39: 418–25.
SIRS, When nonsignificant results are found in trials or meta-analyses, differentiating between no proof of difference (an ‘inconclusive’ result)1 and proof of no difference (equivalence, a ‘conclusive’ result)1 is increasingly recognised to be a crucial step for a correct interpretation.2–4 We have reanalysed the trials examined by Stidham and co-workers5 for the end-point of induction of remission. Firstly, the meta-analysis results were re-expressed using risk difference (RD) rather than relative risk.6 Then, the pooled RDs for direct comparisons of biologics vs placebo were subjected to network meta-analysis. In this way, the pooled values of RD were estimated for the Aliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
