HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.
Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."
Dr. Jean Frederic Colombel
Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.
In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).
"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.
To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."
Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).
Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."
The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).
Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).
A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).
In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).
Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.
Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.
The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.