People with difficult-to-treat rheumatoid arthritis who do not have success with one JAK inhibitor could succeed either by cycling to other JAK inhibitors or switching to a biologic. Both strategies led to comparable control of disease activity in the international JAK-pot cohort study.

The advent of new JAK inhibitors with different inhibition profiles has made it possible to use a second JAK inhibitor if the first fails in patients with rheumatoid arthritis (RA). “In real life, JAK inhibitors are being used primarily in patients who have already failed treatment with a biologic DMARD, and they have shown to be effective in these situations,” Dr. Manuel Pombo-Suarez (Hospital Clinico Universitario Santiago De Compostela, Spain) said.

“There is no data on the effectiveness of using a second JAK inhibitor compared with a biologic DMARD after the failure of a JAK inhibitor.”.

This nested cohort study included prospectively collected data on 708 RA patients from 14 national registries of the JAK-pot collaboration who failed a first JAK inhibitor and were then treated with either a second JAK inhibitor (cycling) or a biologic DMARD (switching) in routine care.1 The researchers compared the effectiveness of both treatment strategies on drug retention and disease activity, measured by DAS-28 disease activity test scores for 1 year after they started their second treatment. Among participants, 154 cycled and 554 switched. Patients cycling JAK inhibitors tended to be older, had longer RA, had already received more biological DMARDs, and had more prolonged exposure to the first JAK inhibitor than those who switched to a biologic. “JAK inhibitor cyclers had a more difficult treatment profile than the others,” Dr. Pombo-Suarez commented.

Cycling and switching showed similar drug survival after 2 years of follow-up. However, the researchers noted an interesting, although not statistically significant, trend: patients who cycled were more likely to discontinue second treatment when they originally stopped their first JAK inhibitor because of side effects rather than ineffectiveness.

Over time, test results of patients’ disease activity improved similarly in the cycling and switching groups, showing improvement after a year. “This was precisely the goal of our study: to refine treatment options after failure to a JAK inhibitor,” said Dr. Pombo-Suarez. “We intend to provide an answer for a growing population of RA patients, those who have failed treatment to JAK inhibitors. A limitation of our study is that most patients received tofacitinib. It will be interesting to see new JAK inhibitors included in the future.” The most important take-away is that the effectiveness of cycling to another JAK inhibitor is no different from that of switching to a biologic DMARD. “Cycling JAK inhibitors is kind of a desperate scenario, but this might change in the future,” Dr. Pombo-Suarez added. “Looking at the results of the study, you see it is a possibility.”


  1. Pombo-Suarez M, et al. Effectiveness of Cycling JAKi Compared to Switching to bDMARD in patients who failed a first JAKi in an international collaboration of registries of rheumatoid arthritis patients (the JAK-pot Study). Abstract 1442. ACR Convergence 2021, 3– November.

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