An updated meta-analysis in 2018 by Olsen and colleagues in Annals of the Rheumatic Diseases showed a pooled incidence ratio of melanoma in patients with RA treated with biologics of 1.7 (95% CI, 1.2 to 2.3) compared with the general population, although there was significant heterogeneity between the included studies.5 There was no statistically significant difference found between patients with RA treated with TNFIs compared with those who were biologic naive (pooled IRR, 1.4; 95% CI, 0.8-2.3).
There are several important points to consider when reviewing this study. The study was a systematic review and meta-analysis, and therefore should be interpreted differently than a prospective study. In addition, this study included analyses using health insurance databases, which are more focused on financial endpoints than on clinical research-based questions.
The results of this study were not adjusted for race, ethnicity, or ultraviolet (UV) light exposure, all of which can impact a patient’s risk for melanoma. In the psoriasis studies, patients may have been previously treated with phototherapy with psoralen-UVA (PUVA), which itself can predispose patients to melanoma and therefore, could be a potential confounding factor. Based on the author’s analysis, it was challenging to determine the duration of therapy for patients receiving conventional systemic therapy.
Ideally, the follow-up time period would have been longer than what was reported in to obtain more long-term data on melanoma risk in these patients. Also, the majority of patients evaluated were receiving TNFIs; however, it would have been interesting to include more patients receiving other agents such as interleukin (IL)-12 and -23 inhibitors (ustekinumab), janus kinase (JAK) inhibitors (tofacitinib), and integrin inhibitors (vedolizumab).
Regardless of the indication, patients treated with TNFIs should undergo a comprehensive skin exam by a dermatologist at least annually. When discussing TNFI therapy with patients, it is important to clearly review the potential cancer risks, such as melanoma, and thoroughly document this discussion in the patient’s medical record.
As there continues to be an increased emphasis on value-based care within the US health care systems, the use of biosimilars could potentially lead to increased access to these medications. It will be valuable to closely follow these patients with long-term studies to evaluate whether or not increased access to these medications leads to any changes in the risks of developing malignancies, including melanoma. As more studies in the future focus on prospective cohorts, it will continue to be challenging to distinguish if the malignancy risks are primarily driven by the medications themselves, the underlying inflammatory processes, or a combination of both.
- Passarelli A, Mannavola F, Stucci LS, Tucci M, Silvestris, F. Immune system and melanoma biology: A balance between immunosurveillance and immune escape. Oncotarget. Oncotarget. 2017;8(62):106132-106142.
- Esse S, Mason KJ, Green AC, Warren, RB. Melanoma risk in patients treated with biologic therapy for common inflammatory diseases: A systematic review and meta-analysis [published online May 20, 2020]. JAMA Dermatol. doi: 10.1001/jamadermatol.2020.1300
- Singh S, Nagpal SJS, MH Murad, et al. Inflammatory bowel disease is associated with an increased risk of melanoma: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12(2):210-208.
- Peleva E, Exton LS, Kelley K, Kleyn CE, Mason KJ, Smith CH. Risk of cancer in patients with psoriasis on biological therapies: A systematic review. Br J Dermatol. 2018;178(1):103-113. doi: 10.1111/bjd.15830.
- Olsen CM, Green AC. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: an updated meta-analysis. Ann Rheum Dis. 2018;77(8):e49.