Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study

• Published in: Alimentary Pharmacology & Therapeutics (Suppl) Vol. 43; no. 2; pp. 252 - 261
• Main Authors: Beaugerie, L., Lémann, Marc, Cadiot, Guillaume, Duclos, Bernard, Bonaz, Bruno, Nion‐Larmurier, Isabelle, Delchier, Jean‐Charles, Chaussade, Stanislas, Coffin, Benoit, Delasalle, Patrick, Souffran, Marc‐Henry, Gouilloud, Sylvie, Savoye, Guillaume, Brazier, Franck, Bensaude, Raoul‐Jacques, Nisard, Andrée, Capelle, Philippe, Dabadie, Alain, Goldfain, Denis, Lemière, Sébastien, Nalet, Bernard, Roux, Jean‐Pol, Reville, Marc, Hugot, Jean‐Pierre, Lescut, Dominique, Ouvry, Dominique, Wittersheim, Christian, Attar, Alain, Guemene, Jean‐Marc, Claude, Pierre, Chatrenet, Philippe, Dubois, Philippe, Pereira, Adelino, Ngo, Yann, Gotlib, Jean Pierre, Raoux, Philippe, Chapoutot, Christian, Mudry, Jean, Bolze, Jean‐Louis, Meurisse, Jean‐Jacques, Bellaiche, Guy, Desurmont, Philippe, Decroix, Bruno, Dib, Nina, Lagier, Emmanuel, Fallourd, Philippe, Delon, Bernard, Arotçarena, Ramuntxo, Broyer, Joel, Godeberge, Béatrice, Puech, Jean, Pornin, Béatrice, Champigneulle, Bruno, David, Xavier‐Richard, Lombard, Frédéric, Hamon, Jean‐François, Vidal, Alain, Coupier, Dominique, Auroux, Jean, Lentini, Franck, Leveque, Anne‐Marie, Tusseau, Frank, Vincent, Edmond, Vitte, René‐Louis, Carwana, Alain, Helbert, Thierry, Barré, Philippe, Jacques, Christian, Kezachian, Gilles, Bismuth, Michaël, Delanoe, Christophe, De Montigny, Stéphanie, Soudan, Denis, Dadamessi, Innocenti, Lenaerts, Catherine, Garret, Marc, Fayemendy, Laurent, Michaudel, Gilles, Missonnier, Gilles, Bourbon, Pierre, Gros, Pascal, Glibert, André, Bineau, Catherine, Hartwig, Johannes, Pelatan, Cécile, Doubremelle, Marie, Roche, Hervé, Chryssostalis, Ariane, Khaddari, Saïd, Gury, Bruno, Wantiez, Michel, Durous, Eric, Gazut, Valérie, Plane, Alain, Croguennec, Bernard, Gelsi, Eve, Ponsot, Philippe, Maroy, Bernard, Dall'Osto, Hélène, De Lustrac, Mercédes
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-01-2016
• Subjects: Adult; Bacteriology; Biochemistry, Molecular Biology; Cancer; Cohort analysis; Cohort Studies; Female; Health risk assessment; Health risks; Humans; Incidence; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Intestine; Kidneys; Life Sciences; Male; Microbiology and Parasitology; Middle Aged; Molecular biology; Observational studies; Patients; Proportional Hazards Models; Prospective Studies; Risk Factors; Urinary tract; Urogenital system; Urologic Neoplasms - epidemiology; Urologic Neoplasms - etiology; Young Adult; Therapy; Association; Nonmelanoma Skin Cancers; Transplantation; Malignancy; Azathioprine; Metaanalysis
• ISSN: 0269-2813; 0953-0673; 1365-2036
• DOI: 10.1111/apt.13466

Summary
Background
The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines.
Aim
To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort.
Methods
Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow‐up was 35 months (IQR: 29–40).
Results
Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient‐years in patients receiving thiopurines (95% CI: 0.21–0.95), 0.10/1000 patient‐years in patients who discontinued thiopurines (95% CI: 0.00–0.56) and 0.30/1000 patient‐years in patients never treated with thiopurines (95% CI: 0.12–0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47–6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01–3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47–12.42, P = 0.78) in patients never treated with thiopurines. The multivariate‐adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04–7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12–14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52–50.03, P = 0.0001).
Conclusion
Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men.