Methotrexate risk for melanoma still uncertain


By Mardi Chapman

12 Mar 2020

Whether methotrexate is associated with an increased risk of melanoma remains uncertain with a Swedish study finding the use of the immunosuppressive drug in psoriasis patients does not increase their melanoma risk.

However the findings contradict Australian evidence from 2008 that methotrexate use by patients with rheumatoid arthritis increases their risk of melanoma about three-fold.

The Swedish study compared 395 patients with psoriasis who developed melanoma between 2010 and 2016 and 3,950 cancer-free patients with psoriasis.

It found methotrexate prescription rates were similar in both groups (25% v 24%).

As well, there was no indication of a dose-response association based on accumulated methotrexate doses and there were no differences in melanoma stages at diagnosis between the MTX-exposed and MTX-unexposed cases.

“The survival rates did not differ between cases and controls (adjusted hazard ratio 14, 95% CI 10–21; P = 0058) and no statistically significant differences were seen between MTX-exposed and MTX-unexposed cases.”

“The adjusted hazard ratios for mortality and melanoma-specific mortality within the case group were 0.7 (95% CI 02–19, P = 044) and 0.8 (95% CI 02–36, P = 076), respectively,” the study said.

“As MTX still constitutes an important drug in the dermatological treatment armamentarium, the results are reassuring for dermatologists treating patients with psoriasis in everyday clinical practice,” it concluded.

Associate Professor Kiarash Khosrotehrani, a clinician-scientist at the University of Queensland’s Centre for Clinical Research, told the limbic the issue was a complex one.

“Basically the only association between melanoma and MTX has been shown in rheumatoid arthritis. But there is a meta-analysis showing that RA by itself regardless of its treatment is associated with increased incidence of melanoma.”

“The only Australian study was on RA and there are none on psoriasis,” he said.

Professor Rachelle Buchbinder, lead author on the 2008 RA study, told the limbic one of its limitations was that it was not population-based.

“We have since published two more papers relating to melanoma risk in people with RA – both from the Australian Rheumatology Association Database (ARAD) – a longitudinal national observational registry.”

“In 2015 we compared risk of malignancy in TNF-treated and biologic naive RA patients compared with the general population. We also found melanoma risk was increased about two-fold in both the TNF-treated and biologic naive RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible.”

“We didn’t find an increased risk of melanoma among TNF-exposed to naive patients suggesting TNF inhibitors are not associated with increased melanoma risk.”

The latest research from the ARAD, published in 2019, no longer found an increased risk of melanoma in either TNF-treated or biologic naive RA patients compared with the general population, she said.

And other studies have had conflicting findings.

“So in summary, we still probably don’t have a definitive answer and exposure to other medicines and patient characteristics like genetic background including skin colour and relatively higher ultraviolet light exposure, may also be important for melanoma risk.”

However given the higher risk for melanoma and non-melanoma skin cancer in Australians, she recommended an annual skin check for patients with RA who were on MTX.

“We have yet to run the same analysis for psoriatic arthritis but we are planning to do that.”

“My practice is also not to start someone on MTX with a history of melanoma. If patients develop a melanoma I will also stop the MTX as there are plenty of other medications that we can use and limited data regarding risk of recurrence if taking MTX.”

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