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Case Study: Potential Link Between JAK Inhibitor and Merkel Cell Carcinoma?

By: Celeste L. Dixon
Posted: Thursday, October 7, 2021

Merkel cell carcinoma is a rare skin cancer, even under usual circumstances, but case-study evidence points to a possible, perhaps even rarer, link between this type of skin cancer and JAK inhibitors such as tofacitinib. In JAAD Case Reports, Aleksandar Krunic, MD, PhD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues described what they consider the fourth known instance of a patient receiving a JAK inhibitor who developed Merkel cell carcinoma, and all, atypically, have been in women younger than age 70. The authors’ patient, who was taking tofacitinib for rheumatoid arthritis, was treated with surgery, radiation, and pembrolizumab; she is being watched carefully and was free of recurrence at 1 year post surgery, they reported.

Merkel cell carcinoma typically arises in immunosuppressed individuals, explained the authors; it is usually twice as common in men, and 80% of cases develop in patients 70 years or older. The incidence rate on the United States is 0.7 per 100,000 person-years.

The patient in this case, aged 60, had been treated for rheumatoid arthritis for a decade with only occasional nonsteroidal anti-inflammatory drugs, but when her disease progressed, she started methotrexate. That was discontinued after 3 months due to nodulosis, and she then began tofacitinib at 11 mg daily. Within 8 months, a lesion that proved to be Merkel cell carcinoma developed on her left forearm and grew rapidly.

Dr. Krunic and colleagues noted three main factors they believe contributed to the development of Merkel cell carcinoma in their patient: the high degree of tofacitinib-induced immunosuppression; her already compromised immune system, due to her rheumatoid arthritis; and her lighter skin type combined with the lesion’s location on a sun-exposed area.

The authors recommended continued surveillance of patients treated with this category of medications. Doing so “may shed more light on long-term risks of such profound immunosuppression involving the JAK-STAT signaling pathway,” they concluded.

Disclosure: The study authors reported no conflicts of interest.



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