Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients

N A Kennedy; Rahul Kalla; B Warner; C J Gambles; R Musy; S Reynolds; R Dattani; H Nayee; R Felwick; R Harris; S Marriott; S M Senanayake; C A Lamb; H Al-Hilou; D R Gaya; P M Irving; J Mansfield; M Parkes; T Ahmad; J R F Cummings; I D Arnott; J Satsangi; A J Lobo; M Smith; J O Lindsay; C W Lees

doi:10.1111/apt.12980

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients

N A Kennedy, Rahul Kalla, B Warner, C J Gambles, R Musy, S Reynolds, R Dattani, H Nayee, R Felwick, R Harris, S Marriott, S M Senanayake, C A Lamb, H Al-Hilou, D R Gaya, P M Irving, J Mansfield, M Parkes, T Ahmad, J R F CummingsI D Arnott, J Satsangi, A J Lobo, M Smith, J O Lindsay, C W Lees

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.

AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.

METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.

RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007).

CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

Original language	English
Journal	Alimentary Pharmacology and Therapeutics
DOIs	https://doi.org/10.1111/apt.12980
Publication status	Published - 6 Oct 2014

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10.1111/apt.12980

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease
© 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 323 KBLicence: Creative Commons: Attribution (CC-BY)

http://onlinelibrary.wiley.com/doi/10.1111/apt.12980/abstract

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Kennedy, N. A., Kalla, R., Warner, B., Gambles, C. J., Musy, R., Reynolds, S., Dattani, R., Nayee, H., Felwick, R., Harris, R., Marriott, S., Senanayake, S. M., Lamb, C. A., Al-Hilou, H., Gaya, D. R., Irving, P. M., Mansfield, J., Parkes, M., Ahmad, T., ... Lees, C. W. (2014). Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.12980

@article{d8f2e1e814e548e6b1be36429e5c0941,

title = "Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients",

abstract = "BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007).CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.",

author = "Kennedy, {N A} and Rahul Kalla and B Warner and Gambles, {C J} and R Musy and S Reynolds and R Dattani and H Nayee and R Felwick and R Harris and S Marriott and Senanayake, {S M} and Lamb, {C A} and H Al-Hilou and Gaya, {D R} and Irving, {P M} and J Mansfield and M Parkes and T Ahmad and Cummings, {J R F} and Arnott, {I D} and J Satsangi and Lobo, {A J} and M Smith and Lindsay, {J O} and Lees, {C W}",

year = "2014",

month = oct,

day = "6",

doi = "10.1111/apt.12980",

language = "English",

journal = "Alimentary Pharmacology and Therapeutics",

issn = "0269-2813",

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}

Kennedy, NA, Kalla, R, Warner, B, Gambles, CJ, Musy, R, Reynolds, S, Dattani, R, Nayee, H, Felwick, R, Harris, R, Marriott, S, Senanayake, SM, Lamb, CA, Al-Hilou, H, Gaya, DR, Irving, PM, Mansfield, J, Parkes, M, Ahmad, T, Cummings, JRF, Arnott, ID, Satsangi, J, Lobo, AJ, Smith, M, Lindsay, JO & Lees, CW 2014, 'Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients', Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.12980

TY - JOUR

T1 - Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease

T2 - relapse and recapture rates, with predictive factors in 237 patients

AU - Kennedy, N A

AU - Kalla, Rahul

AU - Warner, B

AU - Gambles, C J

AU - Musy, R

AU - Reynolds, S

AU - Dattani, R

AU - Nayee, H

AU - Felwick, R

AU - Harris, R

AU - Marriott, S

AU - Senanayake, S M

AU - Lamb, C A

AU - Al-Hilou, H

AU - Gaya, D R

AU - Irving, P M

AU - Mansfield, J

AU - Parkes, M

AU - Ahmad, T

AU - Cummings, J R F

AU - Arnott, I D

AU - Satsangi, J

AU - Lobo, A J

AU - Smith, M

AU - Lindsay, J O

AU - Lees, C W

PY - 2014/10/6

Y1 - 2014/10/6

N2 - BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007).CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

AB - BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007).CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

U2 - 10.1111/apt.12980

DO - 10.1111/apt.12980

M3 - Article

C2 - 25284134

SN - 0269-2813

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

ER -

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients

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