Increased Risk for Nonmelanoma Skin Cancers in Patients Who Receive Thiopurines for Inflammatory Bowel Disease

被引:412
作者
Peyrin-Biroulet, Laurent [1 ,2 ]
Khosrotehrani, Kiarash [3 ]
Carrat, Fabrice [4 ,5 ]
Bouvier, Anne-Marie [6 ]
Chevaux, Jean-Baptiste [1 ,2 ]
Simon, Tabassome [7 ]
Carbonnel, Frank [8 ,9 ]
Colombel, Jean-Frederic [10 ,11 ]
Dupas, Jean-Louis
Godeberge, Philippe [12 ]
Hugot, Jean-Pierre [13 ,14 ,15 ]
Lemann, Marc [16 ]
Nahon, Stephane [17 ]
Sabate, Jean-Marc [18 ,19 ]
Tucat, Gilbert
Beaugerie, Laurent [20 ,21 ]
机构
[1] Henri Poincare Univ, INSERM Unite 954, Univ Hosp Nancy, F-54511 Vandoeuvre Les Nancy, France
[2] Henri Poincare Univ, Dept Gastroenterol, Univ Hosp Nancy, F-54511 Vandoeuvre Les Nancy, France
[3] Univ Queensland Ctr Clin Res, Brisbane, Qld, Australia
[4] Hop St Antoine, AP HP, INSERM UMR S 707, Unit Publ Hlth, F-75571 Paris, France
[5] UMR S 707 UPMC Univ Paris 06, Paris, France
[6] Univ Bourgogne, CHU Dijon, Registre Bourguignon Canc Digestifs, INSERM Unite 866, Dijon, France
[7] Univ Paris 06, AP HP, Serv Pharmacol, Paris, France
[8] Univ Paris 11, Univ Hosp Paris Sud Bicetre, AP HP, INSERM Unite 1018, Paris, France
[9] Univ Paris 11, Univ Hosp Paris Sud Bicetre, AP HP, Dept Gastroenterol, Paris, France
[10] CHU Lille, F-59037 Lille, France
[11] Univ Lille Nord France, Lille, France
[12] Univ Paris 05, Dept Med Chirurg Pathol Digest, Inst Mutualiste Montsouris, Paris, France
[13] Univ Paris Diderot, UMR843, Paris, France
[14] INSERM, UMR 843, Paris, France
[15] Hop Robert Debre, AP HP, F-75019 Paris, France
[16] Hop St Louis, Dept Gastroenterol, Paris, France
[17] GHI Raincy Montfermeil, Montfermeil, France
[18] Hop Louis Mourier, AP HP, Dept Gastroenterol, F-92701 Colombes, France
[19] Univ Paris 07, Paris, France
[20] Hop St Antoine, AP HP, Dept Gastroenterol, F-75571 Paris, France
[21] UPMC Univ Paris 06, Paris, France
关键词
CESAME Study; Therapy; Crohn's Disease; Colitis; ORGAN TRANSPLANT RECIPIENTS; POPULATION-BASED COHORT; NECROSIS FACTOR-ALPHA; BASAL-CELL CARCINOMA; CROHNS-DISEASE; RHEUMATOID-ARTHRITIS; AZATHIOPRINE; IMMUNOSUPPRESSANTS; PREVALENCE; ADALIMUMAB;
D O I
10.1053/j.gastro.2011.06.050
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) who have been exposed to thiopurines might have an increased risk of skin cancer. We assessed this risk among patients in France. METHODS: We performed a prospective observational cohort study of 19,486 patients with IBD, enrolled from May 2004 to June 2005, who were followed up until December 31, 2007. The incidence of nonmelanoma skin cancer (NMSC) in the general population, used for reference, was determined from the French Network of Cancer Registries. RESULTS: Before the age of 50 years, the crude incidence rates of NMSC among patients currently receiving or who previously received thiopurines were 0.66/1000 and 0.38/1000 patient-years, respectively; these values were 2.59/1000 and 1.96/1000 patient-years for the age group of 50 to 65 years and 4.04/1000 and 5.70/1000 patient-years for patients older than 65 years. Among patients who had never received thiopurines, the incidence of NMSC was zero before the age of 50 years, 0.60/1000 for the ages of 50 to 65 years, and 0.84/1000 for those older than 65 years. A multivariate Cox regression model stratified by propensity score quintiles showed that ongoing thiopurine treatment (hazard ratio [HR], 5.9; 95% confidence interval [CI], 2.1-16.4; P=.0006) and past thiopurine exposure (HR, 3.9; 95% CI, 1.3-12.1; P=.02) were risk factors for NMSC. They also identified age per 1-year increase as a risk factor for NMSC (HR, 1.08; 95% CI, 1.05- 1.11; P<.0001). CONCLUSIONS: Ongoing and past exposure to thiopurines significantly increases the risk of NMSC in patients with IBD, even before the age of 50 years. These patients should be protected against UV radiation and receive lifelong dermatologic screening.
引用
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页码:1621 / U150
页数:13
相关论文
共 34 条
[1]
Angelucci E, 2011, INFLAMM BOWEL DIS, V17, P1827, DOI 10.1002/ibd.21278
[2]
Armitage P., 2001, STAT METHODS MED RES, V4th
[3]
Cancer Risk in Patients With Rheumatoid Arthritis Treated With Anti-Tumor Necrosis Factor α Therapies Does the Risk Change With the Time Since Start of Treatment? [J].
Askling, Johan ;
van Vollenhoven, Ronald F. ;
Granath, Fredrik ;
Raaschou, Pauline ;
Fored, C. Michael ;
Baecklund, Eva ;
Dackhammar, Christina ;
Feltelius, Nils ;
Coster, Lars ;
Geborek, Pierre ;
Jacobsson, Lennart T. ;
Lindblad, Staffan ;
Rantapaa-Dahlqvist, Solbritt ;
Saxne, Tore ;
Klareskog, Lars .
ARTHRITIS AND RHEUMATISM, 2009, 60 (11) :3180-3189
[4]
Inflammatory dowel disease, azathioprine and skin cancer: case report and literature review [J].
Austin, AS ;
Spiller, RC .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2001, 13 (02) :193-194
[5]
Interventions for preventing non-melanoma skin cancers in high-risk groups [J].
Bath-Hextall, F. ;
Leonardi-Bee, J. ;
Somchand, N. ;
Webster, A. ;
Delitt, J. ;
Perkins, W. .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2007, (04)
[6]
Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study [J].
Beaugerie, Laurent ;
Brousse, Nicole ;
Bouvier, Anne Marie ;
Colombel, Jean Frederic ;
Lemann, Marc ;
Cosnes, Jacques ;
Hebuterne, Xavier ;
Cortot, Antoine ;
Bouhnik, Yoram ;
Gendre, Jean Pierre ;
Simon, Tabassome ;
Maynadie, Marc ;
Hermine, Olivier ;
Faivre, Jean ;
Carrat, Fabrice .
LANCET, 2009, 374 (9701) :1617-1625
[7]
Adherence to Adalimumab Therapy in Crohn's Disease: A French Multicenter Experience [J].
Billioud, Vincent ;
Laharie, David ;
Filippi, Jerome ;
Roblin, Xavier ;
Oussalah, Abderrahim ;
Chevaux, Jean-Baptiste ;
Hebuterne, Xavier ;
Bigard, Marc-Andre ;
Peyrin-Biroulet, Laurent .
INFLAMMATORY BOWEL DISEASES, 2011, 17 (01) :152-159
[8]
Oxidative damage to DNA: formation, measurement and biochemical features [J].
Cadet, J ;
Douki, T ;
Gasparutto, D ;
Ravanat, JL .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 531 (1-2) :5-23
[9]
Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery [J].
Cosnes, J ;
Nion-Larmurier, I ;
Beaugerie, L ;
Afchain, P ;
Tiret, E ;
Gendre, JP .
GUT, 2005, 54 (02) :237-241
[10]
Multiple cutaneous malignancies arising in a patient with Crohn disease treated with concomitant azathioprine and antitumour necrosis factor-α [J].
Fogo, A. J. ;
Hunt, J. B. ;
Clement, M. .
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 2010, 35 (07) :793-795