'Cycling' JAK inhibitors effective in difficult-to-treat rheumatoid arthritis
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Patients with rheumatoid arthritis who fail their first JAK inhibitor can achieve success with either “cycling” to another JAK inhibitor or switching to a biologic disease-modifying antirheumatic drug, according to data presented at ACR Convergence 2021.
“Most current knowledge of efficacy and safety data of this new class of drugs comes from clinical trials with limited real-world data,” Manuel Pombo-Suarez, MD, PhD, of the Hospital Clinico Universitario of Santiago de Compostela, in Spain, told attendees at a virtual press conference. “In real life, JAK inhibitors are being primarily use in situations where they have already shown efficacy in clinical development. Not all the patients would respond to or tolerate JAK inhibitors in real life. As their use increases, the number of patients who fail treatment with JAK inhibitors is also increasing, and these patients have a difficult to treat profile.”
“We must provide a solution to this growing population,” he added. “Basically, there are two options: After using our first JAK inhibitor, either change to a different JAK inhibitor or to go back to a biologic. The rationale behind cycling JAK inhibitors is that each JAK inhibitor works differently. Each JAK inhibitor has different activities which are likely to affect their efficacy and safety profiles, but these must be demonstrated, and efficacy and safety of cycling jak inhibitors is unknown.”
To compare JAK-inhibitor cycling to switching to a biologic drug among patients with difficult-to-treat RA, Pombo-Suarez and colleagues conducted a nested cohort study of data from 14 national registries. The researchers pooled prospectively collected data on 708 patients who, during routine care, failed their first JAK inhibitor and later moved on with either another JAK inhibitor or a biologic DMARD. In all, 154 included patients cycled to a second JAK inhibitor, while 554 switched to a biologic.
The researchers compared drug retention rates and disease activity, as measured by the DAS28, over 1 year following the start of the second treatment. They used log rank tests to examine differences in drug survival rates, while DAS28 trajectories were predicted based on an age- and gender-adjusted linear mixed model with a quadratic trend over time.
According to the researchers, those who cycled to a second JAK inhibitor were older, demonstrated longer disease duration, received more biologic DMARDs and experienced longer exposure to the first JAK inhibitors than those who switched to a biologic. Monotherapy was more prevalent, with the discontinuation of the initial JAK inhibitor more common for safety reasons than for lack of effectiveness.
Ultimately, both cycling and switching strategies demonstrated similar drug survival rates after 2 years of follow-up.
However, the researchers reported a non-significant trend in which discontinuation was more likely among patients who cycled to another JAK inhibitor when reason for the initial discontinuation was an adverse event. Meanwhile, discontinuation was less likely among patients cycling JAK inhibitors when the reason for stopping the first therapy was ineffectiveness. DAS28 over time was similar, with improvements after 1 year of follow-up, between both strategies.
“If this is confirmed, we think it's going to be relevant,” Pombo-Suarez said. “Meaning that if you have a patient that stops a JAK inhibitor, would you cycle, or would it be wiser to use a different type of treatment? The takeaway message will be that, in a patient with rheumatoid arthritis that faces treatment with a JAK inhibitor, both strategies — cycling JAK inhibitors or switching to a biologic DMARD — appear to have similar effectiveness.”
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Pombo-Suarez M. Abstract 1442. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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