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Melanoma
In the USA, melanoma is the fifth most common cancer for men and the seventh
most common cancer for women. It is responsible for more than 9000 deaths annu-
ally. Overall, the absolute risk of melanoma is much less than that of NMSC, and
thus larger populations are needed in order to evaluate specific medication associa-
tions. As with other skin cancers, there are significant physical, psychological,
financial, and societal costs of melanoma.
The prior literature is limited by the individual sample sizes of many studies.
In a systematic review and meta-analysis, the incidence rate of melanoma in
patients with IBD was 27.5 cases/100,000 person-years (95% CI, 19.9–37.0). IBD
was associated with a 37% increase in risk of melanoma (12 studies; RR, 1.37; 95%
CI, 1.10–1.70). The risk was increased among patients with both CD and UC [ 22 ].
This increased risk predated the biologic era, showing that IBD itself may be associ-
ated with an increased risk of melanoma.
The Quebec claims database study previously referenced for NMSC also
assessed the risk of melanoma. Out of the 19,582 patients who met study inclusion
criteria, a total of 102 cases of melanoma were identified. Neither biologics nor
thiopurines were found to be associated with an increased risk of melanoma [ 18 ].
In contrast, a larger retrospective cohort using LifeLink Health Plan Claims
Database in the USA evaluated 108,579 patients with IBD from 1997 to 2009. In a
nested case-control study of melanoma in patients with IBD, there were 209 cases
of melanoma and 823 matched controls. A total of 26 out of 209 cases of melanoma
had documented biologic use (12.4%) vs. 56 out of 823 controls (6.8%). The use of
any biologic anti- TNF was associated with melanoma in crude (OR, 2.08; 95% CI
1.24–3.51) and adjusted analyses (OR, 1.88; 95% CI 1.08–3.29), while there was
no significant association with any thiopurine or any 5-ASA use. The use, less than
120 days’ duration, showed no associated risk of melanoma (crude OR, 0.97; 95%
CI, 0.19–4.98). Long-term use, as designated by a surrogate marker of current use
of anti- TNF at the time of entry into cohort follow-up, was associated with an
adjusted OR of 3.93 (95% CI, 1.82–8.50) compared to patients not using these
drugs at enrollment [ 23 ].
The link between anti-TNFs and melanoma has been studied more comprehen-
sively in the RA population. A systematic review and meta-analysis by Olsen et al.
evaluated six studies. Four of the studies looked at the risk of melanoma in RA
patients receiving anti-TNF therapy compared to patients treated with non-biologic
DMARDS and found a 1.60 (95% confidence interval, 1.16–2.19) pooled effect
estimate. Five of the studies examined the risk of melanoma in RA patients receiv-
ing ant-TNFs compared to the general population, and the pooled effect estimate
was 1.87 (95% confidence interval, 1.53–2.30). A systematic literature review and
meta-analysis of biologic registers demonstrated the relative risk of melanoma to
be 1.17 (95% CI, 0.86–1.59) [ 24 ]. These findings overall suggest the use of anti-
TNFs is an independent risk factor for the development of melanoma in the RA
population [ 25 ].
J.T. Hughes and M.D. Long