Letters to the Editors
Letter: biological therapies are effective for prevention of post-operative Crohn’s disease recurrence G. Bodini*, C. De Cassan†, V. Savarino* & E. Savarino† *Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. † Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. E-mail: [email protected] doi:10.1111/apt.12831
SIRS, We have read with interest the systematic review by Jones et al.1 regarding use of prophylactic drugs to prevent Crohn’s disease (CD) recurrence after resective surgery. This study tried to summarise the available knowledge on the efficacy and safety of thiopurines and anti-TNF compounds in the post-operative setting, with the aim to modify the natural history of CD. The authors analysed four randomised controlled trials including 433 patients on thiopurine therapy and one involving 24 patients on anti-TNF therapy, concluding that evidence for routine use of thiopurine treatment in post-operative CD is heterogeneous and unconvincing and that evidence for prophylactic anti-TNF use is limited, though promising, being its routine use guided by early assessment of relapse patients. We appreciated the efforts made by the authors to clarify this important area of debate. However, given the authors conducted a systematic review, we are surprised that not all available published data in the literature were quoted. Indeed, following our case series published in 2012, which reported 100% clinical, radiological and endoscopic remission in six anti-TNF-naıve adalimumab (ADA)-treated patients 3 years after surgery for ileal/ileocolonic stricturing,2 we have more recently published the first, randomised, three-armed, mesalazine-controlled study evaluating the rate of endoscopic and clinical recurrence with 2 years of follow-up in CD operated patients treated with ADA, azathioprine or mesalazine.3 In this study, the rate of endoscopic recurrence was significantly lower in the ADA group compared with azathioprine or mesalazine (6.3% vs. 64.7% and 83.3%, respectively). Moreover, there was a significantly lower
322
proportion of patients with clinical recurrence in the ADA group compared with azathioprine or mesalazine (12.5% vs. 64.7% and 50%, respectively). Finally, we provided detailed clinical, radiological and endoscopic data at 1 and 2 years after surgery in patients treated with azathioprine, and we confirmed the limited efficacy of this drug administered as prophylactic treatment in preventing endoscopic and clinical CD recurrence.4 In conclusion our data, together with those published by Regueiro et al.,5 provide strong evidence that anti-TNF drugs are much more effective than the traditional medications in preventing endoscopic and clinical post-operative recurrence of CD and provides a rationale for aggressive post-operative chemoprevention with biological therapy. Further and larger controlled trials are needed to establish the actual impact of this kind of drug on the rate of disease recurrence and the economic impact of this modern approach.
ACKNOWLEDGEMENT Declaration of personal interests: Edoardo Savarino has served as a consultant for Given Imaging; Vincenzo Savarino has served as a speaker for Abbvie, Alfawasserman, Giuliani, Janssen-Cilag, Malesci, Novartis Consumer Health, Nycomed, Reckitt-Benckiser, Takeda. Declaration of funding interests: None. REFERENCES 1. Jones GR, Kennedy NA, Lees CW, et al. Systematic review: the use of thiopurines or anti-TNF in post-operative Crohn’s disease maintenance - progress and prospects. Aliment Pharmacol Ther 2014; 39: 1253–65. 2. Savarino E, Dulbecco P, Bodini G, et al. Prevention of postoperative recurrence of Crohn’s disease by Adalimumab. Eur J Gastroenterol Hepatol 2012; 4: 468–70. 3. Savarino E, Bodini G, Dulbecco P, et al. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease: a randomized controlled trial. Am J Gastroenterol 2013; 108: 1731–42. 4. Peyrin-Biroulet L, Deltenre P, Ardizzone S, et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn’s disease: a meta-analysis. Am J Gastroenterol 2009; 104: 2089–96. 5. Regueiro M, Schraut W, Baidoo L, et al. Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 2009; 136: 441–50.
Aliment Pharmacol Ther 2014; 40: 319-324 ª 2014 John Wiley & Sons Ltd
Letter: biological therapies are effective for prevention of post-operative Crohn’s disease recurrence G. Bodini*, C. De Cassan†, V. Savarino* & E. Savarino† *Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. † Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. E-mail: [email protected] doi:10.1111/apt.12831
SIRS, We have read with interest the systematic review by Jones et al.1 regarding use of prophylactic drugs to prevent Crohn’s disease (CD) recurrence after resective surgery. This study tried to summarise the available knowledge on the efficacy and safety of thiopurines and anti-TNF compounds in the post-operative setting, with the aim to modify the natural history of CD. The authors analysed four randomised controlled trials including 433 patients on thiopurine therapy and one involving 24 patients on anti-TNF therapy, concluding that evidence for routine use of thiopurine treatment in post-operative CD is heterogeneous and unconvincing and that evidence for prophylactic anti-TNF use is limited, though promising, being its routine use guided by early assessment of relapse patients. We appreciated the efforts made by the authors to clarify this important area of debate. However, given the authors conducted a systematic review, we are surprised that not all available published data in the literature were quoted. Indeed, following our case series published in 2012, which reported 100% clinical, radiological and endoscopic remission in six anti-TNF-naıve adalimumab (ADA)-treated patients 3 years after surgery for ileal/ileocolonic stricturing,2 we have more recently published the first, randomised, three-armed, mesalazine-controlled study evaluating the rate of endoscopic and clinical recurrence with 2 years of follow-up in CD operated patients treated with ADA, azathioprine or mesalazine.3 In this study, the rate of endoscopic recurrence was significantly lower in the ADA group compared with azathioprine or mesalazine (6.3% vs. 64.7% and 83.3%, respectively). Moreover, there was a significantly lower
322
proportion of patients with clinical recurrence in the ADA group compared with azathioprine or mesalazine (12.5% vs. 64.7% and 50%, respectively). Finally, we provided detailed clinical, radiological and endoscopic data at 1 and 2 years after surgery in patients treated with azathioprine, and we confirmed the limited efficacy of this drug administered as prophylactic treatment in preventing endoscopic and clinical CD recurrence.4 In conclusion our data, together with those published by Regueiro et al.,5 provide strong evidence that anti-TNF drugs are much more effective than the traditional medications in preventing endoscopic and clinical post-operative recurrence of CD and provides a rationale for aggressive post-operative chemoprevention with biological therapy. Further and larger controlled trials are needed to establish the actual impact of this kind of drug on the rate of disease recurrence and the economic impact of this modern approach.
ACKNOWLEDGEMENT Declaration of personal interests: Edoardo Savarino has served as a consultant for Given Imaging; Vincenzo Savarino has served as a speaker for Abbvie, Alfawasserman, Giuliani, Janssen-Cilag, Malesci, Novartis Consumer Health, Nycomed, Reckitt-Benckiser, Takeda. Declaration of funding interests: None. REFERENCES 1. Jones GR, Kennedy NA, Lees CW, et al. Systematic review: the use of thiopurines or anti-TNF in post-operative Crohn’s disease maintenance - progress and prospects. Aliment Pharmacol Ther 2014; 39: 1253–65. 2. Savarino E, Dulbecco P, Bodini G, et al. Prevention of postoperative recurrence of Crohn’s disease by Adalimumab. Eur J Gastroenterol Hepatol 2012; 4: 468–70. 3. Savarino E, Bodini G, Dulbecco P, et al. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease: a randomized controlled trial. Am J Gastroenterol 2013; 108: 1731–42. 4. Peyrin-Biroulet L, Deltenre P, Ardizzone S, et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn’s disease: a meta-analysis. Am J Gastroenterol 2009; 104: 2089–96. 5. Regueiro M, Schraut W, Baidoo L, et al. Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 2009; 136: 441–50.
Aliment Pharmacol Ther 2014; 40: 319-324 ª 2014 John Wiley & Sons Ltd
