‘The elephant in the room’: Age, disease-related factors may drive JAK safety signals
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SAN DIEGO — Patient age and disease-related factors may be driving safety signals in medications used to treat rheumatoid arthritis and psoriatic disease, according to a speaker at the 2023 Congress of Clinical Rheumatology West.
This is especially relevant when discussing Janus kinase inhibitors, particularly in light of one specific study, said Frank Behrens, MD, of the Fraunhofer Institute for Translational Medicine and Pharmacology at the Goethe-University Frankfurt, in Germany.
“The elephant in the room when talking about JAK inhibitors is the ORAL Surveillance study,” Behrens told attendees, highlighting the risks for cardiovascular events and malignancy reported in that trial.
“The data were generated with tofacitinib (Xeljanz, Pfizer) in RA,” he said. “What is hard for me to understand is what kind of conclusions were made from this study.”
Behrens suggested the study design itself may have contributed to the researchers finding these events. In short, he argued that the point of the study was to recruit patients who may be at increased risk for major adverse cardiovascular events or malignancy.
“That was the plan,” he said. “You wanted to see patients with cardiovascular risk factors.”
Meanwhile, a deeper look into the data may suggest that patients with higher cardiovascular and malignancy risk profiles, along with patients aged older than 65 years, were the ones driving the result showing increased risks compared with TNF inhibition, according to Behrens.
“If patients were without any risk factors, or the lowest risk factor group, there is no clear difference between tofacitinib and TNF inhibitors,” he said. “The message is that patient with atherosclerotic disease, who were older, smokers, these are the patients that had risk with tofacitinib.”
In addition, Behrens stated that a smaller proportion of patients with PsA or psoriasis fall into the high-risk groups.
““It always depends on the baseline characteristics of the patients,” he said. “Studies have shown that disease duration and activity were much more associated with malignancies.”
“Only 10% of the PsA population can expect to have an increased risk of JAK inhibitors compared with biologics with regard to risk for MACE, stroke or cancer,” Behrens added. “Overall, the population fulfilling the risk criteria from the ORAL Surveillance study is very low in PsA and psoriasis populations.”
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Behrens F. How Does the Efficacy of Targeted & Non-Targeted Molecules Vary in Specific Psoriatic Arthritis Subsets? Presented at The Congress of Clinical Rheumatology West; Sept. 7-10, 2023 (hybrid meeting).
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