The biological DMARD abatacept used in the treatment of rheumatoid arthritis patients has been associated with increased rates of non-melanoma skin cancer (NMSC), according to a German study.

The findings, presented at the American College of Rheumatology (ACR) Convergence annual meeting, support similar results from a Swedish registry study which had found an increased risk of squamous cell skin cancer in patients treated with abatacept, a CLTA-4 fusion protein.

Dr Anja Strangfeld, from the German Rheumatism Research Centre in Berlin, told the meeting that 17 SCCs (0.12%) and 118 BCCs (0.85%) were reported in 13,870 patients enrolled in the German RABBIT registry between 2007-2020.

More than half the treatment episodes were with TNF inhibitors (55%), 27.2% with csDMARDs, 23.3% with IL-6 inhibitors, 16.7% with rituximab, 15.6% with JAK inhibitors and 14% with abatacept.

The study found age as well as a higher number of comorbidities were independently associated with the occurrence of NMSC.

Dr Strangfeld said abatacept was the only treatment found to be associated with the occurrence of NMSC.

“But patients initiating this treatment had a higher burden of disease of comorbidities therefore the higher risk of NMSC may be attributed to residual and unmeasured confounding or cumulative effect of therapies when used a second or third line bDMARD,” she said.

Dr Strangfeld added that co-medication with methotrexate also had to be considered.

“In RABBIT, we found a striking variability of methotrexate as a co-medication between different biologic treatments.”

Methotrexate co-medication rates ranged from 68% with abatacept to as low as 36% in the patients treated with IL-6 inhibitors.

She said those results were consistent with other studies such as the CIRT-AE cardiovascular event prevention study which found significantly more skin cancers in methotrexate-treated patients (HR 2.05) and especially squamous cell cancers (HR 3.08).

A US study of methotrexate in patients with cardiovascular or metabolic disease had also found a two-fold increased risk for skin cancer (HR, 2.05).

Dr Strangfeld said the role of methotrexate co-medication had to be analysed further.

Previous investigations into the links between biologics and malignant neoplasms have noted that the immune modulation effects may lower host surveillance against incipient tumours and accelerate cancer progression.