[en] PURPOSE: We aimed to analyse malignancy rates and predictors for the development of malignancies in a large German inflammatory bowel disease (IBD) cohort treated with thiopurines and/or anti-tumour necrosis factor (TNF) antibodies. METHODS: De novo malignancies in 666 thiopurine-treated and/or anti-TNF-treated IBD patients were analysed. Patients (n = 262) were treated with thiopurines alone and never exposed to anti-TNF antibodies (TP group). In addition, patients (n = 404) were exposed to anti-TNF antibodies (TNF+ group) with no (7.4%), discontinued (80.4%) or continued (12.1%) thiopurine therapy. RESULTS: In the TP group, 20 malignancies were observed in 18 patients compared with 8 malignancies in 7 patients in the TNF+ group (hazard ratio 4.15; 95% CI 1.82-9.44; p = 0.0007; univariate Cox regression). Moreover, 18.2% of all patients in the TP group >/=50 years of age developed a malignancy, compared with 3.8% of all patients <50 years of age (p = 0.0008). In the TNF+ group, 6.5% of all patients >/=50 years of age developed malignancies compared with 0.3% of all patients <50 years of age (p = 0.0007). In both groups combined, thiopurine treatment duration >/=4 years was associated with the risk for skin cancer (p = 0.0024) and lymphoma (p = 0.0005). CONCLUSIONS: Our data demonstrate an increased risk for the development of malignancies in IBD patients treated with thiopurines in comparison with patients treated with anti-TNF antibodies with or without thiopurines.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Beigel, Florian
Steinborn, Anni
Schnitzler, Fabian
Tillack, Cornelia
Breiteneicher, Simone
John, Jestinah Mahachie
Van Steen, Kristel ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Laubender, Rudiger P.
Goke, Burkhard
Seiderer, Julia
Brand, Stephan
Ochsenkuhn, Thomas
Language :
English
Title :
Risk of malignancies in patients with inflammatory bowel disease treated with thiopurines or anti-TNF alpha antibodies.
Publication date :
2014
Journal title :
Pharmacoepidemiology and Drug Safety
ISSN :
1053-8569
eISSN :
1099-1557
Publisher :
John Wiley & Sons, Hoboken, United States - New Jersey
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009; 3: 47-91.
Schneeweiss S, Korzenik J, Solomon DH, Canning C, Lee J, Bressler B. Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections. Aliment Pharmacol Ther 2009; 30: 253-264.
Toruner M, Loftus EV, Jr, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134: 929-936.
Steenholdt C, Svenson M, Bendtzen K, Thomsen OO, Brynskov J, Ainsworth MA. Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease. J Crohns Colitis 2012; 6: 108-111.
Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol 1996; 91: 423-433.
Collamer AN, Guerrero KT, Henning JS, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action. Arthritis Rheum 2008; 59: 996-1001.
O'Donovan P, Perrett CM, Zhang X, et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2005; 309: 1871-1874.
Beigel F, Schnitzler F, Paul Laubender R, et al. Formation of antinuclear and double-strand DNA antibodies and frequency of lupus-like syndrome in anti-TNF-alpha antibody-treated patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17: 91-98.
Biancone L, Calabrese E, Petruzziello C, Pallone F. Treatment with biologic therapies and the risk of cancer in patients with IBD. Nat Clin Pract Gastroenterol Hepatol 2007; 4: 78-91.
Smith MA, Irving PM, Marinaki AM, Sanderson JD. Review article: malignancy on thiopurine treatment with special reference to inflammatory bowel disease. Aliment Pharmacol Ther 2010; 32: 119-130.
Zabana Y, Domenech E, Manosa M, et al. Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice. Aliment Pharmacol Ther 2010; 31: 553-560.
Huang ML, Ran ZH, Shen J, Li XB, Xu XT, Xiao SD. Efficacy and safety of adalimumab in Crohn's disease: Meta-analysis of placebo-controlled trials. J Dig Dis 2011; 12: 165-172.
Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005; 54: 1121-1125.
Armstrong RG, West J, Card TR. Risk of cancer in inflammatory bowel disease treated with azathioprine: a UK population-based case-control study. Am J Gastroenterol 2010; 105: 1604-1609.
Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 2007; 56: 2886-2895.
Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009; 374: 1617-1625.
Krathen MS, Gottlieb AB, Mease PJ. Pharmacologic immunomodulation and cutaneous malignancy in rheumatoid arthritis, psoriasis, and psoriatic arthritis. J Rheumatol 2010; 37: 2205-2215.
Vos AC, Bakkal N, Minnee RC, et al. Risk of malignant lymphoma in patients with inflammatory bowel diseases: a Dutch nationwide study. Inflamm Bowel Dis 2011; 17: 1837-1845.
Khan N, Abbas AM, Lichtenstein GR, Loftus EV, Jr., Bazzano LA. Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a nationwide retrospective cohort study. Gastroenterology 2013; 145: 1007-1015 e1003.
Kinlen LJ, Sheil AG, Peto J, Doll R. Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. Br Med J 1979; 2: 1461-1466.
Watorek E, Boratynska M, Smolska D, Patrzalek D, Klinger M. Malignancy after renal transplantation in the new era of immunosuppression. Ann Transplant 2011; 16: 14-18.
Reeve VE, Greenoak GE, Gallagher CH, Canfield PJ, Wilkinson FJ. Effect of immunosuppressive agents and sunscreens on UV carcinogenesis in the hairless mouse. Aust J Exp Biol Med Sci 1985; 63(Pt 6): 655-665.
Kelly GE, Meikle W, Sheil AG. Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice. Transplantation 1987; 44: 429-434.
Frankel HH, Yamamoto RS, Weisburger EK, Weisburger JH. Chronic toxicity of azathioprine and the effect of this immunosuppressant on liver tumor induction by the carcinogen N-hydroxy-N-2-fluorenylacetamide. Toxicol Appl Pharmacol 1970; 17: 462-480.
Cohen SM, Erturk E, Skibba JL, Bryan GT. Azathioprine induction of lymphomas and squamous cell carcinomas in rats. Cancer Res 1983; 43: 2768-2772.
Pedersen N, Duricova D, Elkjaer M, Gamborg M, Munkholm P, Jess T. Risk of extra-intestinal cancer in inflammatory bowel disease: meta-analysis of population-based cohort studies. Am J Gastroenterol 2010; 105: 1480-1487.
Dayharsh GA, Loftus EV, Jr, Sandborn WJ, et al. Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology 2002; 122: 72-77.
Rosh JR, Gross T, Mamula P, Griffiths A, Hyams J. Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn's disease: a cautionary tale? Inflamm Bowel Dis 2007; 13: 1024-1030.
Beigel F, Jurgens M, Tillack C, et al. Hepatosplenic T-cell lymphoma in a patient with Crohn's disease. Nat Rev Gastroenterol Hepatol 2009; 6: 433-436.
Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology 2012; 143: 390-399.e391.
Peyrin-Biroulet L, Khosrotehrani K, Carrat F, et al. Increased Risk For Non-Melanoma Skin Cancers In Patients Who Receive Thiopurines For Inflammatory Bowel Disease. Gastroenterology 2011; 141(5): 1621-28.e1-5.
Maddox JS, Soltani K. Risk of nonmelanoma skin cancer with azathioprine use. Inflamm Bowel Dis 2008; 14: 1425-1431.
Long MD, Kappelman MD, Pipkin CA. Nonmelanoma skin cancer in inflammatory bowel disease: a review. Inflamm Bowel Dis 17: 1423-1427.
Singh H, Nugent Z, Demers AA, Bernstein CN. Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. Gastroenterology 2011; 141: 1612-1620.
Seiderer J, Goke B, Ochsenkuhn T. Safety aspects of infliximab in inflammatory bowel disease patients. A retrospective cohort study in 100 patients of a German University Hospital. Digestion 2004; 70: 3-9.
Zabana Y, Domenech E, Manosa M, et al. Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice. Aliment Pharmacol Ther 31: 553-560.
Fidder H, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut 2009; 58: 501-508.
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002; 359: 1541-1549.
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.
Colombel JF, Sandborn WJ, Panaccione R, et al. Adalimumab safety in global clinical trials of patients with Crohn's disease. Inflamm Bowel Dis 2009; 15: 1308-1319.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol 2006; 4: 621-630.
Caspersen S, Elkjaer M, Riis L, et al. Infliximab for inflammatory bowel disease in Denmark 1999-2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol 2008; 6: 1212-1217; quiz 1176.
de Vries HS, van Oijen MG, de Jong DJ. Serious events with infliximab in patients with inflammatory bowel disease: a 9-year cohort study in the Netherlands. Drug Saf 2008; 31: 1135-1144.
Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-Cell Non-Hodgkin's Lymphomas Reported to the FDA AERS With Tumor Necrosis Factor-Alpha (TNF-alpha) Inhibitors: Results of the REFURBISH Study. Am J Gastroenterol 2013; 108(1): 99-105.
Lichtenstein GR, Rutgeerts P, Sandborn WJ, et al. A Pooled Analysis of Infections, Malignancy, and Mortality in Infliximab- and Immunomodulator-Treated Adult Patients With Inflammatory Bowel Disease. Am J Gastroenterol 2012; 107(7): 1051-63.
Treton X, Bouhnik Y, Mary JY, et al. Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse. Clin Gastroenterol Hepatol 2009; 7: 80-85.
French H, Mark Dalzell A, Srinivasan R, El-Matary W. Relapse rate following azathioprine withdrawal in maintaining remission for Crohn's disease: a meta-analysis. Dig Dis Sci 2011; 56: 1929-1936.
Hamzaoglu H, Cooper J, Alsahli M, Falchuk KR, Peppercorn MA, Farrell RJ. Safety of infliximab in Crohn's disease: a large single-center experience. Inflamm Bowel Dis 2010; 16: 2109-2116.
Hemminki K, Li X, Sundquist J, Sundquist K. Cancer risks in Crohn disease patients. Ann Oncol 2009; 20: 574-580.
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