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Reply to Professor Taylor
JCF-01030; No of Pages 2
www.elsevier.com/locate/jcf
Letter to the Editor
Reply to Professor Taylor Daniel Peckham ⁎, Paul Whitaker Leeds Adult Cystic Fibrosis Unit, St. James's University Hospital, Leeds, UK Received 1 March 2014; accepted 1 March 2014
We would agree with Professor Taylor that the role of methacrylic acid co-polymer (used as an enteric coating, Eudragit, in certain brands of pancreatic enzymes) in developing fibrosing colonopathy (FC) is unclear and controversial [1]. The initial clinical report and subsequent epidemiological study linking FC to certain brands of high strength enzymes formed the basis of the subsequent advice of the Committee on Safety of Medicines (CSM)/Medicine control Agency (MCA) [2–4]. It was advised that the high strength enzymes Pancrease HL, Nutrizym 22 and Panzytrat 25,000 should not be used in children aged 15 years or less with cystic fibrosis (CF) and doses of more than 10,000 IU lipase per kg body weight per day of any preparation should be avoided. Since this advice, only three CF children in the UK have developed FC [5]. All were receiving Nutrizym GR, a low strength preparation but coated with Eudragit. In contrast, in the US, advice was to avoid high strength preparations containing more than 20,000 IU lipase per capsule and a total lipase intake of more than 10,000 IU/kg/day; there was no advice on brands [6]. However, despite this advice cases of FC continued to be reported to the US CF Foundation [7]. There appear to be other factors that are relevant to the development of cases of FA. From the evidence available, Eudragit may have contributed and avoidance has resulted in the disappearance of FC in children in the UK. It has been suggested that a high intake of lipase in itself is not a risk factor in the absence of methacrylic acid copolymer [8,9]. This seems to be supported by the absence of further UK cases despite the continuing high intake of predominantly Creon preparations in the UK, both standard and high strength [10], and Creon 25,000 in one paediatric CF centre [11].
⁎ Corresponding author. Tel.: + 44 1132067179. E-mail address: [email protected] (D. Peckham).
As the vast majority of children with FC had been receiving well in excess of 10,000 IU lipase/kg/day, we would reinforce Professor Taylor's advice to continue to follow the guidelines of the MCA/CSM [2,3,12]. Yours sincerely, Dr Daniel Peckham Dr Paul Whitaker Consultant Respiratory Physicians We would like to acknowledge the personal communication with Dr James Littlewood OBE and the History of Cystic Fibrosis Medicine. References [1] Dodge JA. Concerns about records of fibrosing colonopathy study. Lancet 2001;357:1526–7. [2] Smyth RL, van Velzen D, Smyth AR, Lloyd DA, Heaf DP. Strictures of the ascending colon in cystic fibrosis and high strength pancreatic enzymes. Lancet 1994;343:85–6. [3] Smyth RL, Ashby D, O'Hea U, Burrows E, Lewis P, van Velzen D, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-controlled study. Lancet 1995;346:1247–51. [4] Committee on Safety of Medicines. Report of the Pancreatic Enzymes Working Party; 1995 (London). [5] Jones R, Franklin K, Spicer R, Berry J. Colonic strictures in children with cystic fibrosis on low strength pancreatic enzymes. Lancet 1995;346:1230. [6] Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Consensus Committee. J Pediatr 1995;127:681–4. [7] Stevens JC, Davis M, Pawel BR, Zerin JM, Crisci K, Brooks M. Fibrosing colonopathy — a retrospective analysis of US cases 1995–1999. Pediatr Pulmonol 2001;Suppl. 22 [Poster 501]. [8] Prescott P, Bakowski MT. Pathogenesis of fibrosing colonopathy: the role of methacrylic acid copolymer. Pharmacoepidemiol Drug Saf 1999;8:377–84. [9] Bakowski MT, Prescott P. Patterns of use of pancreatic enzyme supplements in fibrosing colonopathy: implications for pathogenesis. Pharmacoepidemiol Drug Saf 1997;6:347–58.
http://dx.doi.org/10.1016/j.jcf.2014.03.001 1569-1993/© 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Peckham D, Whitaker P, Reply to Professor Taylor, J Cyst Fibros (2014), http://dx.doi.org/10.1016/j.jcf.2014.03.001
2
Letter to the Editor
[10] Mehta A. Further comments on fibrosing colonopathy study. Lancet 2001;358:1547–8. [11] Connett GJ, Lucas JS, Atchley JTM, Fairhurst JJ, Rolles CJ. Colonic wall thickening is related to age and not dose of high strength pancreatic microspheres in children with cystic fibrosis. Eur J Gastroenterol Hepatol 1999;11:181–3.
[12] FitzSimmons SC, Burkhart GA, Borowitz D, Grand RJ, Hammerstrom T, Durie PR, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med May 1 1997;336(18):1283–9.
Please cite this article as: Peckham D, Whitaker P, Reply to Professor Taylor, J Cyst Fibros (2014), http://dx.doi.org/10.1016/j.jcf.2014.03.001
www.elsevier.com/locate/jcf
Letter to the Editor
Reply to Professor Taylor Daniel Peckham ⁎, Paul Whitaker Leeds Adult Cystic Fibrosis Unit, St. James's University Hospital, Leeds, UK Received 1 March 2014; accepted 1 March 2014
We would agree with Professor Taylor that the role of methacrylic acid co-polymer (used as an enteric coating, Eudragit, in certain brands of pancreatic enzymes) in developing fibrosing colonopathy (FC) is unclear and controversial [1]. The initial clinical report and subsequent epidemiological study linking FC to certain brands of high strength enzymes formed the basis of the subsequent advice of the Committee on Safety of Medicines (CSM)/Medicine control Agency (MCA) [2–4]. It was advised that the high strength enzymes Pancrease HL, Nutrizym 22 and Panzytrat 25,000 should not be used in children aged 15 years or less with cystic fibrosis (CF) and doses of more than 10,000 IU lipase per kg body weight per day of any preparation should be avoided. Since this advice, only three CF children in the UK have developed FC [5]. All were receiving Nutrizym GR, a low strength preparation but coated with Eudragit. In contrast, in the US, advice was to avoid high strength preparations containing more than 20,000 IU lipase per capsule and a total lipase intake of more than 10,000 IU/kg/day; there was no advice on brands [6]. However, despite this advice cases of FC continued to be reported to the US CF Foundation [7]. There appear to be other factors that are relevant to the development of cases of FA. From the evidence available, Eudragit may have contributed and avoidance has resulted in the disappearance of FC in children in the UK. It has been suggested that a high intake of lipase in itself is not a risk factor in the absence of methacrylic acid copolymer [8,9]. This seems to be supported by the absence of further UK cases despite the continuing high intake of predominantly Creon preparations in the UK, both standard and high strength [10], and Creon 25,000 in one paediatric CF centre [11].
⁎ Corresponding author. Tel.: + 44 1132067179. E-mail address: [email protected] (D. Peckham).
As the vast majority of children with FC had been receiving well in excess of 10,000 IU lipase/kg/day, we would reinforce Professor Taylor's advice to continue to follow the guidelines of the MCA/CSM [2,3,12]. Yours sincerely, Dr Daniel Peckham Dr Paul Whitaker Consultant Respiratory Physicians We would like to acknowledge the personal communication with Dr James Littlewood OBE and the History of Cystic Fibrosis Medicine. References [1] Dodge JA. Concerns about records of fibrosing colonopathy study. Lancet 2001;357:1526–7. [2] Smyth RL, van Velzen D, Smyth AR, Lloyd DA, Heaf DP. Strictures of the ascending colon in cystic fibrosis and high strength pancreatic enzymes. Lancet 1994;343:85–6. [3] Smyth RL, Ashby D, O'Hea U, Burrows E, Lewis P, van Velzen D, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-controlled study. Lancet 1995;346:1247–51. [4] Committee on Safety of Medicines. Report of the Pancreatic Enzymes Working Party; 1995 (London). [5] Jones R, Franklin K, Spicer R, Berry J. Colonic strictures in children with cystic fibrosis on low strength pancreatic enzymes. Lancet 1995;346:1230. [6] Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Consensus Committee. J Pediatr 1995;127:681–4. [7] Stevens JC, Davis M, Pawel BR, Zerin JM, Crisci K, Brooks M. Fibrosing colonopathy — a retrospective analysis of US cases 1995–1999. Pediatr Pulmonol 2001;Suppl. 22 [Poster 501]. [8] Prescott P, Bakowski MT. Pathogenesis of fibrosing colonopathy: the role of methacrylic acid copolymer. Pharmacoepidemiol Drug Saf 1999;8:377–84. [9] Bakowski MT, Prescott P. Patterns of use of pancreatic enzyme supplements in fibrosing colonopathy: implications for pathogenesis. Pharmacoepidemiol Drug Saf 1997;6:347–58.
http://dx.doi.org/10.1016/j.jcf.2014.03.001 1569-1993/© 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Peckham D, Whitaker P, Reply to Professor Taylor, J Cyst Fibros (2014), http://dx.doi.org/10.1016/j.jcf.2014.03.001
2
Letter to the Editor
[10] Mehta A. Further comments on fibrosing colonopathy study. Lancet 2001;358:1547–8. [11] Connett GJ, Lucas JS, Atchley JTM, Fairhurst JJ, Rolles CJ. Colonic wall thickening is related to age and not dose of high strength pancreatic microspheres in children with cystic fibrosis. Eur J Gastroenterol Hepatol 1999;11:181–3.
[12] FitzSimmons SC, Burkhart GA, Borowitz D, Grand RJ, Hammerstrom T, Durie PR, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med May 1 1997;336(18):1283–9.
Please cite this article as: Peckham D, Whitaker P, Reply to Professor Taylor, J Cyst Fibros (2014), http://dx.doi.org/10.1016/j.jcf.2014.03.001