Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in crohn’s disease

Cochrane Database of Systematic Reviews

Volumn 2019, Issue 8, 2019, Pages

  Gjuladin Hellon, Teuta ^a   Iheozor Ejiofor, Zipporah ^a   Gordon, Morris ^a,b   Akobeng, Anthony K ^c  

^a UNIVERSITY OF CENTRAL LANCASHIRE   (United Kingdom)

^b BLACKPOOL VICTORIA HOSPITAL   (United Kingdom)

^c SIDRA MEDICAL AND RESEARCH CENTER   (Qatar)

Author keywords

[No Author keywords available]

Indexed keywords

ADALIMUMAB; AMINOSALICYLIC ACID; AZATHIOPRINE; INFLIXIMAB; LIVER ENZYME; MERCAPTOPURINE; MESALAZINE; PLACEBO; PURINE DERIVATIVE; TUMOR NECROSIS FACTOR INHIBITOR; IMMUNOSUPPRESSIVE AGENT;

ABDOMINAL PAIN; ABSCESS; ADVERSE EVENT; ANEMIA; ARTHRALGIA; ATOPIC DERMATITIS; BRONCHITIS; CLINICAL OUTCOME; COMPARATIVE EFFECTIVENESS; CROHN DISEASE; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; DYSPNEA; ENDOSCOPY; EPIGASTRIC DISCOMFORT; FLATULENCE; FOLLOW UP; HISTOPATHOLOGY; HUMAN; INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE; LEUKOPENIA; MAINTENANCE THERAPY; NAUSEA AND VOMITING; OUTCOME ASSESSMENT; PANCREATITIS; POSTOPERATIVE CARE; PRIORITY JOURNAL; QUALITY OF LIFE; QUALITY OF LIFE ASSESSMENT; RADIOGRAPHY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RELAPSE; REMISSION; REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; SYSTEMATIC REVIEW; TRANSITIONAL CELL CARCINOMA; TREATMENT DURATION; MAINTENANCE CHEMOTHERAPY; PROCEDURES; SECONDARY PREVENTION;

AZATHIOPRINE; CROHN DISEASE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MAINTENANCE CHEMOTHERAPY; MERCAPTOPURINE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REMISSION INDUCTION; SECONDARY PREVENTION;

EID: 85071774200     PISSN: 14651858     EISSN: None     Source Type: Journal    
DOI: 10.1002/14651858.CD010233.pub3     Document Type: Review

References (86)

1. Ardizzone S, Maconi G, Sampietro GM, Russo A, Radice E, Colombo E, et al. Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn’s disease. Gastroenterology 2004;127(3):730–40.
2. Armuzzi A, Felice C, Marzo M, Pugliese D, Andrisani G, Papa A, et al. Prevention of postoperative recurrence with azathioprine or anti-TNF alpha in patients with Crohn’s disease: A pilot study. Digestive and Liver Disease 2012;44: S194.
3. Armuzzi A, Felice C, Marzo M, Pugliese D, Andrisani G, Papa A, et al. Infliximab is more effective than azathioprine in the long-term prevention of postoperative recurrence of Crohn’s disease. Gastroenterology April 2015;1:S856.
4. Armuzzi A, Felice C, Marzo M, Pugliese D, Andrisani G, Papa A, et al. Prevention of postoperative recurrence with azathioprine or anti-TNF alpha in patients with Crohn’s disease: An open-label pilot study. Gastroenterology 2012; 142(5 Suppl 1):S780.
5. ∗ Armuzzi A, Felice C, Papa A, Marzo M, Pugliese D, Andrisani G, et al. Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn’s disease: an open-label pilot study. Journal of Crohn’s and Colitis 2013;7(12):e623–9.
6. ∗ D’Haens G, Vermeire S, Van Assche G, Noman M, Aerden I, Van Olmen G, et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn’s disease: a controlled randomized trial. Gastroeneterology 2008;135(4):1123–9.
7. D’Haens GR, Noman M, Van Assche GA, Van Olmen G, Aerden I, Vermeire S, et al. Combination therapy with metronidazole and azathioprine reduces severe postoperative recurrence of Crohn’s disease: A double-blind controlled randomized trial. Gastroenterology 2007 2007;132(4 Suppl 1):A52.
8. Hanauer SB, Korelitz BI, Rutgeerts P, Peppercorn MA, Thisted RA, Cohen RD, et al. Postoperative maintenance of Crohn’s disease remission with 6-mercaptopurine, mesalamine or placebo: a 2-year trial. Gastroenterology 2004;127(3):723–9.
9. Korelitz B, Hanauer S, Rutgeerts P, Present D, Peppercorn M. Post-operative prophylaxis with 6-MP, 5-ASA or placebo inCrohn’s disease: A 2 year multicenter trial. Gastroenterology 1998;114(4 Part 2):A486.
10. Dilger K, Schaeffeler E, Lukas M, Strauch U, Herfarth H, Muller R, et al. Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn’s disease during 1 year of treatment with azathioprine or mesalazine. Therapeutic Drug Monitoring 2007;29(1):1–5.
11. ∗ Herfarth H, Obermeier F, Tjaden C, Lukas M, Serclova Z, Dignass AU, et al. Double-blind, double dummy, randomized, multicentre, comparative study on the efficacy and safety of azathioprine (AZA) versus mesalazine (5-ASA) for prevention of postoperative endoscopic recurrence in Crohn’s disease. Gastroenterology 2006;130(4 Suppl 2): A480–1.
12. Herfarth H, Tjaden C, Lukas M, Obermeier F, Dilger K, Muller R, et al. Adverse events in clinical trials with azathioprine and mesalamine for the prevention of postoperative recurrence of Crohn’s disease. Gut 2006;55 (10):1526–6.
13. Muller R, Herfarth H. More information on 2006 study published in Gut. Email to Morris Gordon 2/5/2012.
14. ∗ Lopez-Sanroman A, Vera-Mendoza I, Domenech E, Taxonera C, Vega V, Marin-Jimenez I, et al. Adalimumab vs azathioprine in the prevention of postoperative Crohn’s disease recurrence. A GETECCU randomised trial. Journal of Crohn’s and Colitis 2017;11(11):1293-301.
15. Lopez-Sanroman A, Vera-Mendoza I, Domenech E, Taxonera C, Vega V, Marin-Jimenez I, et al. Apprecia: Adalimumab vs azathioprine in the prevention of Crohn’s disease recurrence after surgical resection. A geteccu multicenter randomized trial. United European Gastroenterology Journal 2015;1:A3.
16. NCT01564823. Adalimumab on Preventing Post-chirurgic Recurrence on Crohn’s Disease (APPRECIA). clinicaltrials.gov/ct2/show/NCT01564823 (accessed 28 March 2012).
17. Taxonera C, López-Sanromán A, Vera-Mendoza I, Domènech E, Ruiz VV, Marín-Jiménez I, et al. Quality of life during one year of postoperative prophylactic drug therapy after intestinal resection in Crohn’s patients: Results of the APPRECIA trial. Digestive and Liver Disease 2019;51 (4):529–35.
18. Arnott I, Mowat C, Ennis H, Keerie C, Lewis S, Cahill A, et al. The toppic trial: A randomised, double-blind parallel group trial of mercaptopurine vs placebo to prevent recurrence of Crohn’s disease following surgical resection in 240 patients. Gut 2016;65(Suppl 1):A43–4.
19. Arnott I, Mowat C, Ennis H, Keerie C, Lewis S, Kennedy N, et al. The TOPPIC trial: A randomised, double-blind parallel-group trial of mercaptopurine versus placebo to prevent recurrence of Crohn’s disease following surgical resection in 240 patients. Journal of Crohn’s and Colitis 2016;10(1 Supplement):S21–S22.
20. Arnott I, Mowat C, Ennis H, Keerie C, Lewis S, Kennedy N, et al. The toppic trial: A randomized, double-blind parallel group trial of mercaptopurine vs placebo to prevent recurrence of Crohn’s disease following surgical resection in 240 patients. Gastroenterology 2016;150(4 Suppl 1):S182.
21. Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn’s disease following surgical resection. isrctn.com/ ISRCTN89489788 (accessed 22 February 2007).
22. Mowat C, Arnott I, Cahill A, Smith M, Ahmad T, Subramanian S, et al. Mercaptopurine versus placebo to prevent recurrence of Crohn’s disease after surgical resection (TOPPIC): A multicentre, double-blind, randomised controlled trial. Lancet 2016;1(4):273–82.
23. Angelberger S, Schaeffeler E, Teml A, Petritsch W, Shonova O, Lukas M, et al. Mucosal improvement in patients with moderate to severe postoperative endoscopic recurrence of Crohn’s disease and azathioprine metabolite levels. Inflammatory Bowel Diseases 2013;19:590–8.
24. Angelberger S, Schaeffeler E, Teml A, Petritsch W, Shonova O, Lukas M, et al. Relationship between thiopurine metabolite levels and endoscopic improvement in patients with postoperative moderate to severe endoscopic recurrence of Crohn’sdisease. Gastroenterology 2010;138(5 Suppl 1): S685.
25. Preventing postoperative relapse in Crohn’s disease patients at risk: Azathioprine versus mesalazine. clinicaltrials.gov/ct2/show/NCT00946946 (accessed 27 July 2009).
26. Reinisch W, Angelberger S, Petritsch W, Herrlinger K, Shonova O, Lukas M, et al. A double-blind, double-dummy,randomized, controlled, multicenter trial on the efficacy and safety of azathioprine vs mesalamine for prevention of clinical relapses in Crohn’s disease patients with postoperative moderate or severe endoscopic recurrence. Gastroenterology 2008;134(4 Suppl 1):A70.
27. ∗ Reinisch W, Angelberger S, Petritsch W, Shonova O, Lukas M, Bar-Meir S, et al. Azathioprine versus mesalazine for the prevention of postoperative clinical recurrence in patients with Crohn’s disease with endoscopic recurrence: efficacy and safety results of a randomized, double-blind, double-dummy, multicentre trial. Gut 2010;59(6):752–9.
28. Reinisch W, Angelberger S, Petritsch W, Shonova O, Lukas M, Greinwald R, et al. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in Crohn’s disease patients with endoscopic recurrence: Follow-up data of a randomised, double-blind, double-dummy, 1-year, multicentre trial. Journal of Crohn’s and Colitis 2013;7:S254.
29. Reinisch W, Stange EF. Efficacy of azathioprine versus mesalazine in postoperative Crohn’s disease-the authors’ response. Gut 2011;60(5):739–40.
30. Bodini G, Pellegatta G, Giannini EG, Savarino V, Savarino EV. Adalimumab therapy rather than azathioprine and mesalamine is able to halt Crohn’s disease progression after resective surgery and a post-hoc analysis of a prospective randomized study. Gastroenterology. 2017; Vol. 152, issue 5 Supplement:S774.
31. Savarino E, Bodini G, Dulbecco P, Assandri L, Bruzzone L, Mazza F. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease-a randomized trial. Digestive and Liver Disease 2013;45:S94–5.
32. ∗ Savarino E, Bodini G, Dulbecco P, Assandri L, Bruzzone L, Mazza F, et al. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease: a randomized controlled trial. American Journal of Gastroenterology 2013;108(11): 1731–42.
33. Savarino E, Bodini G, Dulbecco P, Marabotto E, Assandri L, Bruzzone L. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease-a randomized trial. Gastroenterology 2013; 144(5 Suppl 1):S21.
34. NCT01629628. Adalimumab for the Management of Postoperative Crohn’s Disease (CD) POPART. clinicaltrials.gov/ct2/show/NCT01629628 (accessed 27 June 2012).
35. Scapa E, Maharshak N, Kariv Y, Ben-Horin S, White ID, Santo E, et al. Early initiation of adalimumab significantly diminishes post-operative Crohn’s disease recurrence, and is superior to immunomodulator therapy. Preliminary results from the POPART trial. Gastroenterology 2015;148 (4 Supplement):S240–1.
36. ∗ Ferrante M, Papamichael K, Duricova D, D’Haens G, Vermeire S, Archavlis E, et al. Systematic versus Endoscopy-driven Treatment with Azathioprine to Prevent Postoperative Ileal Crohn’s Disease Recurrence. Journal of Crohn’s and Colitis 2015;9(8):617–24.
37. Ferrante M, Papamichael K, Duricova D, D’Haens G, Vermeire S, Archavlis E, et al. Systematic versus endoscopy-driven treatment with azathioprine to prevent postoperative ileal Crohn’s disease recurrence. Journal of Crohn’s and Colitis 2014;8:S205–6.
38. Ferrante M, Papamichael K, Duricova D, D’Haens GR, Vermeire S, Archavlis EJ, et al. Systematic versus endoscopy-driven treatment with azathioprine to prevent postoperative ileal crohn’s disease recurrence: Interim results from a randomized, multicenter trial. Gastroenterology 2014;146(5 Suppl 1):S592.
39. Manosa M, Cabre E, Bernal I, Esteve M, Garcia-Planella E, Ricart Gomez E. Azathioprine versus azathioprine plus metronidazole for the prevention of postoperative endoscopic recurrence of Crohn’s disease: A randomized, placebo controlled trial. Journal of Crohn’s and Colitis 2012; 6:S93.
40. Mañosa M, Cabré E, Bernal I, Esteve M, Garcia-Planella E, Ricart E, et al. Addition of metronidazole to azathioprine for the prevention of postoperative recurrence of Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Inflammatory Bowel Diseases 2013;19(9):1889–95.
41. NCT01876264. Crohn’s extent of resection trial. clinicaltrials.gov/ct2/show/NCT01876264 (accessed 12 June 2013).
42. NCT02247258. Azathioprine in the prevention of ileal Crohn’s disease postoperative recurrence. clinicaltrials.gov/ ct2/show /NCT02247258(accessed 23 September 2014).
43. Nos P, Hinojosa J, Aguilera V, Moles JR, Pastor M, Ponce J, et al. Azathiprine and 5-ASA in the prevention of postoperative recurrence in Crohn’s disease. Gastroenterología y Hepatología 2000;23(8):374–8.
44. Reinisch W, Angelberger S, Petritsch W, Shonova O, Lukas M, Greinwald R, et al. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in Crohn’s disease patients with endoscopic recurrence: Follow-up data of a randomised, double-blind, double-dummy, 1-year, multicentre trial. Journal of Crohn’s and Colitis 2013;7:S254.
45. Robb PM, Sorrentino D. Long-term prevention of postoperative Crohn’s disease recurrence with azathioprine: the wolf in the sheep clothing. International Journal of Colorectal Disease 2015;30(2):283–4.
46. Vidigal FM, de Souza GS, Chebli LA, da Rocha Ribeiro TC, Furtado MC, Castro AC, et al. Azathioprine is more effective than mesalazine at preventing recurrent bowel obstruction in patients with ileocecal Crohn’s disease. Medical Science Monitor 2014;20:2165–70.
47. Wright EK, Cruz P, Kamm MA, Hamilton AL, Ritchie KJ, Krejany S, et al. Intestinal resection in Crohn’s disease is associated with significant and durable improvement in health related quality of life although to a lesser extent in women and smokers. Results from the POCER study. Gastroenterology 2014;146(5 Suppl 1):S435.
48. Wright EK, Kamm MA, Cruz P, Hamilton AL, Ritchie K, Bell SJ, et al. Structured post-operative treatment and monitoring to prevent Crohn’s disease recurrence is cost effective. Results from the POCER study. Journal of gastroenterology and hepatology 2015;30:145.
49. NCT01015391. Efficacy study of T2 versus AZA to maintain clinical and endoscopic remission in postoperative Crohn’s disease. clinicaltrials.gov/ct2/show/NCT01015391 (accessed 18 November 2009).
50. ∗ Zhu W, Li Y, Gong J, Zuo L, Zhang W, Cao L, et al. Tripterygium wilfordii Hook. f. versus azathioprine for prevention of postoperative recurrence in patients with Crohn’s disease: a randomized clinical trial. Digestive & Liver Disease 2015;47(1):14–9.
51. NCT03185611. Effectiveness of rifaximin combined with thiopurine on preventing postoperative recurrence in Crohn’s disease. clinicaltrials.gov/ct2/show/NCT03185611 (accessed 14 June 2017).
52. NL1344. Azathioprine maintenance treatment versus infliximab maintenance treatment in Crohn’s disease patients in remission (Azorix trial). trialregister.nl/trial/1344 (accessed 1 August 2008).
53. Abraham C, Cho JHN. Inflammatory Bowel Disease. New England Journal of Medicine 2009;361(21):2066–78.
54. Axelrad JE, Roy A, Lawlor G, Korelitz B, Lichtiger S. Thiopurines and inflammatory bowel disease: current evidence and a historical perspective. World Journal of Gastroenterology 2016;22:101–3.
55. Benchimol EI, Seow CH, Otley AR, Steinhart AH. Budesonide for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2009, Issue 1. DOI: 10.1002/14651858.CD002913.pub2
56. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Annals of Surgery 2000;231(1):38–45.
57. Boreinstein 2009 Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. Chichester, West Sussex, UK: John Wiley & Sons Ltd, 2009.
58. Camus M, Seksik P, Bourrier A, Nion-Larmurier I, Sokol H. Long-term outcome of patients with Crohn’s disease who respond to azathioprine. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2013;11(4):389–394.
59. Chande N, Patton PH, Tsoulis DJ, Thomas BS, MacDonald JK. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2015, Issue 10. DOI: 10.1002/14651858.CD000067.pub3
60. Colonna T, Korelitz BI. The role of leukopenia in the 6-mercaptopurine induced remission of refractory Crohn’s disease. American Journal of Gastroenterology 1994;89(3): 362–6.
61. Doherty G, Bennett G, Patil S, Cheifetz A, Moss AC. Interventions for prevention of post-operative recurrence of Crohn’s disease. Cochrane Database of Systematic Reviews 2009, Issue 4. DOI: 10.1002/14651858.CD006873.pub2
62. Egger M, Davey-Smith G, Altman D (Editors). Systematic reviews in health care: Meta-analysis in context. Second Edition. London.: BMJ Publishing Group, 2001.
63. Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002;50(4):485–89.
64. Gionchetti P, Dignass A, Danese S, Dias FJM, Rogler G, Lakatos PL, et al. on behalf of ECCO. 3rd European Evidenced-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 2; Surgical Management and Special Situations. Journal of Crohn’s and Colitis February 2017;11(2):135–49.
65. Gjuladin-Hellon T, Gordon M, Iheozor-Ejiofor Z, Akobeng AK. Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2019, Issue 6. DOI: 10.1002/14651858.CD008414.pub3
66. Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd European evidence-based consensus on the management of Crohn’s disease 2016: Part 1: Diagnosis and medical management.. Journal of Crohn’s & Colitis 2017;11:3–25.
67. Gordon M, Naidoo K, Thomas AG, Akobeng AK. Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2011, Issue 1. DOI: 10.1002/14651858.CD008414.pub2
68. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924–6.
69. Hafraoui S, Dewit O, Marteau P, Cosnes J, Colombel JF, Modigliani R, et al. Mycophenolate mofetil in refractory Crohn’s disease after failure of treatments by azathioprine or methotrexate [Le mycophénolate mofétil dans les formes chroniques actives de la maladie de Crohn après échec de lazathioprine ou du méthotrexate]. Gastroenterologie Clinique et Biologique 2002;26(1):17–22.
70. Hanauer SB, Sandborn W. Management of Crohn’s disease in adults. American Journal of Gastroenterology 2001;96(3): 635–43.
71. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
72. Lennard L, Loon JA, Weinshilboum RM. Pharmacogenitics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clinical Pharmacology and Therapeutics 1989;46(2):149–54.
73. Lennard L. The clinical pharmacology of 6-mercaptopurine. European Journal of Clinical Pharmacology 1992;43(4): 329–39.
74. National Institute of Health and Care Excellence. Crohn’s Disease: management (CG152). Available: https://www.nice.org.uk/guidance/cg152/evidence/addendum-pdf-2489565421 2016.
75. Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pasci M, et al. Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 2009;136 (2):441-50.
76. Rolfe 2006 Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall FJ. Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2006, Issue 4. DOI: 10.1002/14651858.CD004826.pub2
77. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology 1990;99(4):956–63.
78. Sahasranaman S, Howard D, Roy S. Clinical pharmacology and pharmacogenetics of thiopurines. European Journal ofClinical Pharmacology 2008;64:753–67.
79. Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. American Journal of Gastroenterology 1996;91(3):423–33.
80. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
81. Steinhart AH, Ewe K, Griffiths AM, Modigliani R, Thomsen OO. Corticosteroids for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2003, Issue 4. DOI: 10.1002/14651858.CD000301
82. Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F. Methods for meta-analysis in medical research. Chichester, West Sussex, UK: John Wiley & Sons Ltd, 2000.
83. Timmer A, Patton PH, Chande N, McDonald JW, MacDonald JK. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2016, Issue 5. DOI: 10.1002/14651858.CD000478.pub4
84. Weinshilboum RN, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. American Journal of Human Genetics 1980;32(5):651–62.
85. Williams JG, Wong WD, Rothenberger DA, Goldberg SM. Recurrence of Crohn’s disease after resection. British Journal of Surgery 1990;78(1):10–9.
86. Gordon M, Taylor K, Akobeng AK, Thomas AG. Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2014, Issue 8. DOI: 10.1002/14651858.CD010233.pub2