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

doi:10.1053/j.gastro.2011.06.050

Gastroenterology

Volume 141, Issue 5, November 2011, Pages 1621-1628.e5

https://doi.org/10.1053/j.gastro.2011.06.050 Get rights and content

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.

Section snippets

CESAME Cohort Design and Population

The analysis of NSMC was restricted to cases occurring during prospective follow-up in the CESAME French nationwide observational cohort. The CESAME cohort was designed to assess the risk of any cancer or high-grade dysplasia in patients with IBD. Details on the design and conduct of the cohort are available elsewhere.⁵ In brief, from May 2004 to June 2005, 680 French gastroenterologists (38.4% with full-time hospital practice, 24.3% mixed with public/private practice, and 37.3% with full-time

Incidence of NMSC and Impact of Thiopurine Exposure

Characteristics of the patient population are given in Table 2. During the 49,719 patient-years of follow-up, 32 patients were diagnosed with incident NMSC. These 32 cases of NMSC represented 11.1% of all incident cancers observed in the CESAME cohort. Crude incidence rates of NMSC are shown in Figure 1, both for the overall IBD population and according to thiopurine treatment status.

Table 3 shows the standardized incidence ratio for NMSC according to thiopurine status at diagnosis of NMSC. An

Discussion

This is the first prospective study of the influence of thiopurines on the risk of NMSC in a nationwide cohort of patients with IBD. The results show that both current and past thiopurine exposure significantly increases this risk.

The impact of thiopurines on the risk of skin cancers has been the subject of considerable controversy, but only case series and retrospective studies based on administrative data had previously been available.^12–17 In a cohort study of 53,377 patients with IBD, the

Acknowledgments

The list of CESAME Study Group investigators appears in the Supplementary Appendix.

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: Conflicts of interest The authors disclose no conflicts.

: Funding Supported by grants from Programme Hospitalier de Recherche Clinique National (AOM05157), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-AP-HP, Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie.

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Original ResearchClinical—Alimentary TractIncreased Risk for Nonmelanoma Skin Cancers in Patients Who Receive Thiopurines for Inflammatory Bowel Disease

Background & Aims

Methods

Results

Conclusions

Section snippets

CESAME Cohort Design and Population

Incidence of NMSC and Impact of Thiopurine Exposure

Discussion

Acknowledgments

Lancet

Lancet

Lancet

Lancet

Clin Gastroenterol Hepatol

Mutat Res

Optimizing thiopurine therapy in inflammatory bowel disease

Inflamm Bowel Dis

Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery

Gut

Impact of azathioprine and tumour necrosis factor antagonists on the need for surgery in newly diagnosed Crohn's disease

Gut

Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates

Gut

Risk of nonmelanoma skin cancer with azathioprine use

Inflamm Bowel Dis

Prevalence of a history of skin cancer in 2007: results of an incidence-based model

Arch Dermatol

Malignant lymphomas in transplantation patients

Transplant Proc

The risk of non-melanoma skin cancer in patients with inflammatory bowel disease using thiopurines is not increased

Clin Gastroenterol Hepatol

Inflammatory bowel disease, azathioprine and skin cancer: case report and literature review

Eur J Gastroenterol Hepatol

Multiple cutaneous malignancies arising in a patient with Crohn disease treated with concomitant azathioprine and antitumour necrosis factor-alpha

Clin Exp Dermatol

Multiple and fulminant cutaneous squamous cell carcinomas in a Crohn's disease patient treated with immunosuppressants and adalimumab

Inflamm Bowel Dis

Original Research
Clinical—Alimentary Tract
Increased Risk for Nonmelanoma Skin Cancers in Patients Who Receive Thiopurines for Inflammatory Bowel Disease