Etiology

In ulcerative colitis, current use of thiopurines was associated with nonmelanoma skin cancer Clinical impact ratings:

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Abbas AM, Almukhtar RM, Loftus EV, Lichtenstein GR, Khan N. Risk of melanoma and non-melanoma skin cancer in ulcerative colitis patients treated with thiopurines: a nationwide retrospective cohort. Am J Gastroenterol. 2014;109:1781-93.

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Question

Commentary

In patients with ulcerative colitis, are thiopurines associated with nonmelanoma skin cancer (NMSC) or melanoma skin cancer (MSC)?

Ulcerative colitis can seriously affect a patient's quality of life, and our therapeutic goal is effective control of the inflammatory burden. Thiopurines, either alone or combined with other medications such as anti–tumor-necrosis factor agents, are part of optimal treatment for controlling inflammation in ulcerative colitis. However, thiopurines have been associated with potential risk for infections and cancer (1-3). Research clarifying the benefits and risks of these medications is critical. In a well-validated retrospective cohort, Abbas and colleagues found a 2-fold increased risk for NMSC with current use of thiopurines. The study population was mostly older white men, which potentially limits the generalizability of the results. For example, thiopurine treatment in younger patients, who have a lower baseline incidence of NMSC, may not yield the same findings.

Methods Design: Retrospective cohort study with linkage of Veterans Affairs Health Care System databases. Setting: Population-based study in the USA. Patients: 14 527 patients (median age 59 y, 94% men, 77% white, median follow-up 8 y) who had ulcerative colitis (≥ 4 ulcerative colitis International Classification of Diseases, 9th revision, codes and ≥ 3 filled prescriptions for 5-aminosalicylic acid [oral or rectal mesalamine, sulfasalazine, balsalazide, or olsalazine]) and were followed for ≥ 6 months between 1 Oct 2001 and 1 Oct 2011. Risk factors: Current use (period from first prescription fill to end of supply or < 6 mo between prescription periods) or previous use (period from completion of last fill or > 6 mo between prescription periods) of thiopurines (azathioprine or 6-mercaptopurine) compared with no use (no prescription or period before first prescription). A patient could contribute to each phase. Analyses were adjusted for age, sex, race, clinic visits/y, and geographic ultraviolet index zone. Outcomes: NMSC and MSC (based on pathology, diagnostic, and surgical treatment codes).

To better understand how these results should influence the use of thiopurines in inflammatory bowel disease, the absolute risk should be considered. In this retrospective cohort, the baseline risk for NMSC was 2.2%. The importance of a 2-fold increase in such a small risk is debatable but certainly more relevant in patients with higher baseline risk (e.g., fair skin, personal or family history of NMSC). Risk for NMSC increased with duration of exposure, and stopping thiopurines seemed to eliminate this risk. These important findings will help guide the use of these agents in a time-dependent way, particularly when used in combination with anti–tumor-necrosis factor agents. Brian Bressler, MD, MS, FRCPC University of British Columbia Vancouver, British Columbia, Canada

Main results 3346 patients (23%) received thiopurines. 421 patients had NMSC and 45 had MSC. Current but not previous use of thiopurines increased risk for NMSC (Table). The incidence rate increased with duration of thiopurine use. Use of thiopurines was not associated with risk for MSC (Table).

Conclusion In patients with ulcerative colitis, current but not past use of thiopurines was associated with nonmelanoma skin cancer; use of thiopurines was not associated with melanoma skin cancer. Source of funding: Department of Veterans Affairs.

References 1. Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501-23. 2. 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;32:119-30. 3. Ariyaratnam J, Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2014;109:163-9.

For correspondence: Dr. A.M. Abbas, University of Florida, Gainesville, FL, USA. E-mail [email protected]fl.edu. 

Association between thiopurine use and skin cancer in patients with ulcerative colitis* Outcomes Thiopurine exposure NMSC

None

n

Number of cases

Adjusted hazard ratio (95% CI)

14 527

317

Current

3346

77

1.0 (reference group) 2.1 (1.6 to 2.6)

Previous

2152

27

0.7 (0.5 to 1.0)

Unadjusted incidence rate ratio (CI) MSC

14 527

37

Current

None

3346

6

1.0 (reference group) 1.5 (0.6 to 3.4)

Previous

2152

2

0.5 (0.1 to 1.8)

*MSC = melanoma skin cancer; NMSC = nonmelanoma skin cancer; other abbreviations defined in Glossary. Hazard ratio adjusted for age, sex, race, clinic visits/y, and geographic ultraviolet index zone.

姝 2015 American College of Physicians

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ACP Journal Club

Annals of Internal Medicine

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17 March 2015

ACP journal club. In ulcerative colitis, current use of thiopurines was associated with nonmelanoma skin cancer.

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