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Published in: Digestive Diseases and Sciences 2/2017

01-02-2017 | Original Article

Rate and Predictors of Mucosal Healing in Ulcerative Colitis Treated with Thiopurines: Results of a Multicentric Cohort Study

Authors: Caroline Prieux-Klotz, Stéphane Nahon, Aurelien Amiot, Leila Sinayoko, Carole Galéano-Cassaz, Stanislas Chaussade, Romain Coriat, Pierre Lahmek, Vered Abitbol

Published in: Digestive Diseases and Sciences | Issue 2/2017

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Abstract

Background and Aims

Mucosal healing (MH) with thiopurines has been poorly investigated in ulcerative colitis (UC). We aimed to assess MH rate in UC patients treated with thiopurine monotherapy.

Patients and Methods

We retrospectively collected all UC patients treated with thiopurines more than 6 months who have undergone colonoscopy at baseline and after at least 6 months of treatment. Patients were recruited from January 2005 to May 2015 through a personal database and/or standardized hospital inpatient diagnostic dataset. Patients were excluded in case of any use of other immunomodulator or biological agent. MH was defined as a Mayo endoscopic subscore ≤1 and UCEIS ≤ 2. Histological healing (HH) was defined by the absence of epithelial polynuclear infiltrate, cryptic abscesses, or ulcerations.

Results

Eighty patients (31 women, median age 43 [IQR 32–58]) were included. Median disease duration was 10.5 [6–16] years. At baseline, median full Mayo score, endoscopic subscore, and UCEIS were 8 [6.8–10], 3 [2–3], and 5 [3–6], respectively. MH was first assessed after a mean follow-up of 38 ± 31 months. Median full Mayo score, endoscopic subscore, and UCEIS decreased to 3.5 [1–6], 2 [0–2.2], and 2 [0–4], respectively. MH was achieved in 43.7%, HH in 38%. In multivariate analysis, predictors of MH were thiopurine exposure duration ≥2 years [odds ratio (OR) 2.9, CI 95% (1.1–7.6), p = 0.03] and a prior acute severe colitis [OR 5.9, CI 95% (1.1–32), p = 0.04]. Factors associated with MH during treatment were partial Mayo score ≤2 (NPV = 100%), BMI ≥ 25 kg/m2 (NPV = 75%), and MCV ≥ 95 fL (NPV = 73%).

Conclusions

In UC, thiopurine monotherapy is associated with MH in 43.7% and HH in 38%.
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Literature
1.
go back to reference Klotz C, Barret M, Dhooge M, et al. Management of diagnosis and treatment in ulcerative colitis. Presse Méd. 2015;44:144–149.CrossRefPubMed Klotz C, Barret M, Dhooge M, et al. Management of diagnosis and treatment in ulcerative colitis. Presse Méd. 2015;44:144–149.CrossRefPubMed
2.
go back to reference Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6:991–1030.CrossRefPubMed Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6:991–1030.CrossRefPubMed
3.
go back to reference López-Palacios N, Mendoza JL, Taxonera C, et al. Mucosal healing for predicting clinical outcome in patients with ulcerative colitis using thiopurines in monotherapy. Eur J Intern Med. 2011;22:621–625.CrossRefPubMed López-Palacios N, Mendoza JL, Taxonera C, et al. Mucosal healing for predicting clinical outcome in patients with ulcerative colitis using thiopurines in monotherapy. Eur J Intern Med. 2011;22:621–625.CrossRefPubMed
4.
go back to reference Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194–1201.CrossRefPubMed Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194–1201.CrossRefPubMed
5.
go back to reference Laharie D, Filippi J, Roblin X, et al. Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: a multicenter experience. Aliment Pharmacol Ther. 2013;37:998–1004.CrossRefPubMed Laharie D, Filippi J, Roblin X, et al. Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: a multicenter experience. Aliment Pharmacol Ther. 2013;37:998–1004.CrossRefPubMed
6.
go back to reference Gupta RB, Harpaz N, Itzkowitz S, et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology. 2007;133:1099–1105.CrossRefPubMedPubMedCentral Gupta RB, Harpaz N, Itzkowitz S, et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology. 2007;133:1099–1105.CrossRefPubMedPubMedCentral
7.
go back to reference Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–459.CrossRefPubMed Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–459.CrossRefPubMed
8.
go back to reference Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2014;12:929–934. Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2014;12:929–934.
9.
go back to reference Kruis W, Kiudelis G, Rácz I, et al. Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial. Gut. 2009;58:233–240.CrossRefPubMed Kruis W, Kiudelis G, Rácz I, et al. Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial. Gut. 2009;58:233–240.CrossRefPubMed
10.
go back to reference Bokemeyer B, Hommes D, Gill I, et al. Mesalazine in left-sided ulcerative colitis: efficacy analyses from the PODIUM trial on maintenance of remission and mucosal healing. J Crohns Colitis. 2012;6:476–482.CrossRefPubMed Bokemeyer B, Hommes D, Gill I, et al. Mesalazine in left-sided ulcerative colitis: efficacy analyses from the PODIUM trial on maintenance of remission and mucosal healing. J Crohns Colitis. 2012;6:476–482.CrossRefPubMed
11.
go back to reference Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.CrossRefPubMed Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.CrossRefPubMed
12.
go back to reference Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–265.CrossRefPubMed Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–265.CrossRefPubMed
13.
go back to reference Ardizzone S, Maconi G, Russo A, et al. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006;55:47–53.CrossRefPubMedPubMedCentral Ardizzone S, Maconi G, Russo A, et al. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006;55:47–53.CrossRefPubMedPubMedCentral
14.
go back to reference Timmer A, McDonald JWD, Tsoulis DJ, et al. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012;9:CD000478. Timmer A, McDonald JWD, Tsoulis DJ, et al. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012;9:CD000478.
15.
go back to reference Yamada S, Yoshino T, Matsuura M, et al. Efficacy and safety of long-term thiopurine maintenance treatment in japanese patients with ulcerative colitis. Intest Res. 2015;13:250–258.CrossRefPubMedPubMedCentral Yamada S, Yoshino T, Matsuura M, et al. Efficacy and safety of long-term thiopurine maintenance treatment in japanese patients with ulcerative colitis. Intest Res. 2015;13:250–258.CrossRefPubMedPubMedCentral
16.
go back to reference Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146:392–400.CrossRefPubMed Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146:392–400.CrossRefPubMed
17.
go back to reference Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:5A–36A.CrossRefPubMed Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:5A–36A.CrossRefPubMed
18.
go back to reference Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666.CrossRefPubMedPubMedCentral Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666.CrossRefPubMedPubMedCentral
19.
go back to reference Travis SPL, Schnell D, Krzeski P, et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012;61:535–542.CrossRefPubMed Travis SPL, Schnell D, Krzeski P, et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012;61:535–542.CrossRefPubMed
20.
go back to reference Bressenot A, Salleron J, Bastien C, et al. Comparing histological activity indexes in UC. Gut. 2015;64:1412–1418.CrossRefPubMed Bressenot A, Salleron J, Bastien C, et al. Comparing histological activity indexes in UC. Gut. 2015;64:1412–1418.CrossRefPubMed
21.
go back to reference D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763–786.CrossRefPubMed D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763–786.CrossRefPubMed
22.
go back to reference Sutherland L, Roth D, Beck P, et al. Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis. Cochrane Database Syst Rev. 2000;CD000544. doi:10.1002/14651858.CD000544. Sutherland L, Roth D, Beck P, et al. Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis. Cochrane Database Syst Rev. 2000;CD000544. doi:10.​1002/​14651858.​CD000544.
23.
go back to reference Sandborn WJ, Feagan BG, PURSUIT-Maintenance Study Group, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109.CrossRefPubMed Sandborn WJ, Feagan BG, PURSUIT-Maintenance Study Group, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109.CrossRefPubMed
24.
go back to reference Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M, et al. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol. 2010;7:15–29.CrossRefPubMed Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M, et al. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol. 2010;7:15–29.CrossRefPubMed
25.
go back to reference Travis SPL, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013;145:987–995.CrossRefPubMed Travis SPL, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013;145:987–995.CrossRefPubMed
26.
go back to reference Travis SPL, Schnell D, Feagan BG, et al. The impact of clinical information on the assessment of endoscopic activity: characteristics of the Ulcerative Colitis Endoscopic Index Of Severity [UCEIS]. J Crohns Colitis. 2015;9:607–616.CrossRefPubMedPubMedCentral Travis SPL, Schnell D, Feagan BG, et al. The impact of clinical information on the assessment of endoscopic activity: characteristics of the Ulcerative Colitis Endoscopic Index Of Severity [UCEIS]. J Crohns Colitis. 2015;9:607–616.CrossRefPubMedPubMedCentral
27.
go back to reference Feagan BG, Rutgeerts P, GEMINI 1 Study Group, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.CrossRefPubMed Feagan BG, Rutgeerts P, GEMINI 1 Study Group, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.CrossRefPubMed
28.
go back to reference Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–787.CrossRefPubMed Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–787.CrossRefPubMed
29.
go back to reference Manginot C, Baumann C, Peyrin-Biroulet L. An endoscopic Mayo score of 0 is associated with a lower risk of colectomy than a score of 1 in ulcerative colitis. Gut. 2014;64:1181–1182.PubMed Manginot C, Baumann C, Peyrin-Biroulet L. An endoscopic Mayo score of 0 is associated with a lower risk of colectomy than a score of 1 in ulcerative colitis. Gut. 2014;64:1181–1182.PubMed
31.
go back to reference Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2015;65:408–414.CrossRefPubMed Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2015;65:408–414.CrossRefPubMed
32.
go back to reference Chhaya V, Saxena S, Cecil E, et al. The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989–2009. Aliment Pharmacol Ther. 2015;41:87–98.CrossRefPubMed Chhaya V, Saxena S, Cecil E, et al. The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989–2009. Aliment Pharmacol Ther. 2015;41:87–98.CrossRefPubMed
33.
go back to reference Sood R, Ansari S, Clark T, et al. Long-term efficacy and safety of azathioprine in ulcerative colitis. J Crohns Colitis. 2015;9:191–197.CrossRefPubMed Sood R, Ansari S, Clark T, et al. Long-term efficacy and safety of azathioprine in ulcerative colitis. J Crohns Colitis. 2015;9:191–197.CrossRefPubMed
34.
go back to reference Solberg IC, Lygren I, Jahnsen J, et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol. 2009;44:431–440.CrossRefPubMed Solberg IC, Lygren I, Jahnsen J, et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol. 2009;44:431–440.CrossRefPubMed
35.
go back to reference Lee H-S, Yang S-K, Soh JS, et al. Short- and long-term outcomes of acute severe ulcerative colitis in Korea: the 1999–2005 Cohort. Inflamm Bowel Dis. 2015;21:1825–1831.CrossRefPubMed Lee H-S, Yang S-K, Soh JS, et al. Short- and long-term outcomes of acute severe ulcerative colitis in Korea: the 1999–2005 Cohort. Inflamm Bowel Dis. 2015;21:1825–1831.CrossRefPubMed
36.
go back to reference O’Byrne S, Keir ME, Cabanski CR et al. Rectal bleeding accurately reflects level of mucosal inflammation in patients with ulcerative colitis. Gastroenterology. 2015; 4:Su 1220. O’Byrne S, Keir ME, Cabanski CR et al. Rectal bleeding accurately reflects level of mucosal inflammation in patients with ulcerative colitis. Gastroenterology. 2015; 4:Su 1220.
37.
go back to reference Bouguen G, Sninsky C, Tang KL, et al. Change in erythrocyte mean corpuscular volume during combination therapy with azathioprine and infliximab is associated with mucosal healing: a post hoc analysis from SONIC. Inflamm Bowel Dis. 2015;21:606–614.CrossRefPubMed Bouguen G, Sninsky C, Tang KL, et al. Change in erythrocyte mean corpuscular volume during combination therapy with azathioprine and infliximab is associated with mucosal healing: a post hoc analysis from SONIC. Inflamm Bowel Dis. 2015;21:606–614.CrossRefPubMed
38.
go back to reference Thapa SD, Hadid H, Usman M, et al. Predictors of thiopurine treatment failure in biologic-naïve ulcerative colitis patients. Dig Dis Sci. 2016;61:230–237.CrossRefPubMed Thapa SD, Hadid H, Usman M, et al. Predictors of thiopurine treatment failure in biologic-naïve ulcerative colitis patients. Dig Dis Sci. 2016;61:230–237.CrossRefPubMed
39.
go back to reference Sahasranaman S, Howard D, Roy S. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008;64:753–767.CrossRefPubMed Sahasranaman S, Howard D, Roy S. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008;64:753–767.CrossRefPubMed
Metadata
Title
Rate and Predictors of Mucosal Healing in Ulcerative Colitis Treated with Thiopurines: Results of a Multicentric Cohort Study
Authors
Caroline Prieux-Klotz
Stéphane Nahon
Aurelien Amiot
Leila Sinayoko
Carole Galéano-Cassaz
Stanislas Chaussade
Romain Coriat
Pierre Lahmek
Vered Abitbol
Publication date
01-02-2017
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2017
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-016-4374-0

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