The link between biologic drugs for inflammatory disease and melanoma risk is still murky, according to a systematic review and meta-analysis.
In a comparison of nearly 35,000 individuals on biologic treatment and some 135,000 treated with conventional systemic therapy, the former group trended toward a slightly increased risk for melanoma, Shamarke Esse, MRes, of the University of Manchester in England, and colleagues wrote in JAMA Dermatology.
Despite this trend toward an increased risk for developing melanoma, the differences weren’t statistically significant for those with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), or psoriasis:
- IBD: pooled relative risk 1.20 (95% CI 0.60-2.40)
- RA: pRR 1.20 (95% CI 0.83-1.74)
- Psoriasis: hazard ratio 1.57 (95% CI 0.61-4.09)
“The findings suggest that a clinically meaningful increase in melanoma risk cannot be ruled out,” the researchers warned. “[G]iven the generally long latency period between causal exposure and the development of melanoma, follow-up periods for biologic-treated patients in the included studies may not have been long enough and could have resulted in an underestimation of risk.”
Short-term safety for biologic drugs, which typically target immune system components, has been well established, but longer-term cancer risk remains a concern, Esse and colleagues observed. Melanoma is a particular worry because it is “highly immunogenic” and thus could be unleashed with immunosuppressive treatments, particularly tumor necrosis factor (TNF) inhibitors.
Esse’s group drew upon seven studies published between 2007 and 2019 — two of which looked at patients with IBD, four looking at patients with RA, and one study on patients with psoriasis. The follow-up periods of the studies ranged between one year to 5.48 years.
Biologic therapies used in these studies included rituximab (Rituxan), abatacept (Orencia), etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). Controls in the analysis were those treated with nonbiologic systemic therapies such as methotrexate.
The meta-analysis was limited by a small number of disease-specific studies, including only one study on psoriasis, the researchers pointed out. But one strength of the study was that this was a “more robust and clinically relevant analysis” than prior studies in people specifically with IBD because they restricted the comparison between biologic-treated patients with only biologic-naive patients with IBD. Another limitation of the analysis was how most of the included studies were unable to adjust for melanoma risk factors such as UV radiation exposure, race, and ethnicity.
To address these lingering concerns, Esse’s group suggested future prospective cohort studies report on patients’ treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, as well as the diagnosis date of melanoma.
Last Updated May 20, 2020
Esse is funded by a Psoriasis Association PhD studentship. Other authors reported relationships with Janssen, LEO Pharma, Lilly, Novartis, AbbVie, Almirall, Amgen, Celgene, Pfizer, Arena, Avillion, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, and UCB.