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The top journal in rheumatism Ann Rheum Dis. recently published a study to explore "the best treatment strategy for RA patients after the first JAKi failure". In the
study, disabling JAKi and switching to other JAKi or bDMARDs has a similar effect in reducing disease activity
. However, in the -corrected analysis, the drug retention rate of switched to other JAKi was higher
. However, if the drug was discontinued due to , JAKi's adverse event, then subsequent JAKi treatment is more likely to be discontinued for this reason.
With the emergence of Janus kinase inhibitor (JAKi), the therapeutic drugs for rheumatoid arthritis (RA) have been further expanded. JAKi with different targets of action have been released one after another, making it possible for RA patients to use other JAKi after poor response to the first JAKi. In clinical practice, JAKi is mainly used in RA patients who fail to treat antirheumatic drugs (bDMARDs). However, for the first patients who failed JAKi treatment, the subsequent use of other JAKi is still bDMARDs, and efficacy data is still lacking to guide clinical decision-making.
Recently, Ann Rheum Dis., the top journal in the field of rheumatism, published a study. Foreign scholars compared the efficacy of JAKi or bDMARDs in RA patients after the first JAKi failure based on data from the JAK-pot project.
Research Methods
This study data is derived from the International Cooperation Project (JAK-pot) of 17 national registries. Data from RA patients who failed JAKi treatment and were subsequently treated with other JAKi (JAKi cycle group, n=365) or bDMARDs ( switched biologics group, n=1635). The main result is drug retention, and the secondary result is the change in the cause of drug discontinuation and the clinical disease activity index (CDAI) over time. Kaplan-Meier and cox regression were used to analyze potential confounders of drug retention, and the changes in CDAI over time were simulated using the linear regression model , and the confounders were corrected.
study results
Compared with patients who switched to biologics, the patients in the JAKi circulation group were older, had a longer course of disease, more seropositive, had more history of previous bDMARDs treatment, and the first JAKi treatment time was longer. Most patients used tofatib (61.5%) or baritinib (37.2%) as the first JAKi, uppatinib or filgotinib was limited (1.4%).
followed by other JAKi with higher drug retention rates
Based on 2-year follow-up data, the two treatment strategies showed similar drug retention rates (Figure 1). However, after adjusting for confounding factors, the drug retention rate in the JAKi circulation group was significantly higher than that in the biologics group, with the HR of discontinuation of the drug was 0.82 (95% CI: 0.68-0.99, p=0.04).
Figure 1 Overall Kaplan-Meier curve
The reason for the subsequent treatment of
is related to the reason for the first JAKi
analysis shows that the reason for the first JAKi is the lack of efficacy, most patients in the subsequent two treatment groups will also stop the drug due to poor efficacy. If the first JAKi is discontinued due to adverse events (AE), then subsequent JAKi treatment is more likely to be discontinued due to AE.
The two treatment strategies have improved CDAI compared with the improvement of
2 months of follow-up data, the two treatment strategies have improved CDAI compared with the improvement of patients. The mean CDAI improvement in the JAKi circulation group was 10.8 (95%CI: 3.4-18.2), while the mean CDAI improvement in the switched biologic group was 10.4 (95%CI: 3.1-17.7) (p=0.79). study conclusions
Currently, there is almost no clinical evidence to support the management recommendations of RA patients after JAKi treatment failure. This large international observational study investigates the best treatment strategy for RA patients after the first JAKi failure. The study found that after discontinuing JAKi, switching to other JAKi or bDMARDs had similar effects in reducing disease mobility, while in the correction analysis, the drug retention rate of other JAKi treatment was slightly higher. However, when the first JAKi is discontinued due to adverse events, subsequent JAKi is more likely to be discontinued due to adverse events. This may suggest that may be a more reasonable choice for patients who disable JAKi due to adverse events to switch to bDMARDs.
References: Pombo-Suarez M, Sanchez-Piedra C, Gómez-Reino J,et al. After JAK inhibitor failure: to cycle or to switch, that is the question - data from the JAK-pot collaboration of registries[J]. Ann Rheum Dis. 2022 Sep 13:annrheumdis-2022-222835. doi: 10.1136/ard-2022-222835. Epub ahead of print. PMID: 36100351.
