After JAK inhibitor failure: to cycle or to switch, that is the question – data from the JAK-pot collaboration of registries

Abstract

ObjectivesThe expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi.MethodsThis is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders.Results365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies.ConclusionsAfter failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

Jack pot! What can we learn about registries with respect to treatment cycling in rheumatoid arthritis?

“…If the first JAKi was discontinued due to an adverse event (AE) and the reason for stopping the second JAKi was more likely another AE. 1 Based on these observations, one could conclude that either strategy is reasonable in the difficult to treat patient with RA who had failed multiple advanced therapies.…”

“…Janet E Pope , 1 Roy M Fleischmann 2 An analysis of the Janus kinases (JAK)-pot collaboration of registries, recently reported on the comparative effectiveness of cycling JAK inhibitors (JAKi) compared with switching to a biological diseasemodifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA) after failure to the first JAKi in a nested cohort of patients. 1 Of the registries contributing to the pooled data, 15 were from Europe and the remaining 2 were from Canada and Israel. 1 A strength of this analysis is that much can be learnt from combining datasets as the sample size allows for more power, more questions may be answered, and, most importantly, generalisability is increased.…”

“…1 Of the registries contributing to the pooled data, 15 were from Europe and the remaining 2 were from Canada and Israel. 1 A strength of this analysis is that much can be learnt from combining datasets as the sample size allows for more power, more questions may be answered, and, most importantly, generalisability is increased.…”

“…An analysis of the Janus kinases (JAK)-pot collaboration of registries, recently reported on the comparative effectiveness of cycling JAK inhibitors (JAKi) compared with switching to a biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA) after failure to the first JAKi in a nested cohort of patients 1. Of the registries contributing to the pooled data, 15 were from Europe and the remaining 2 were from Canada and Israel 1.…”

“…When the reason for stopping the first JAKi was lack of efficacy, most of the patients in both treatment groups also stopped for this reason (difference between groups: p=0.59). If the first JAKi was discontinued due to an adverse event (AE) and the reason for stopping the second JAKi was more likely another AE 1…”