Cycling JAKi after poor response in rheumatoid arthritis better than switching to bDMARD
Key takeaways:
- Patients with rheumatoid arthritis who cycled JAK inhibitors after inadequate response had a 38.7% remission rate vs. 2.2% after switching to a biologic DMARD.
- Retention and safety were comparable between the two.
For patients with rheumatoid arthritis and inadequate response to JAK inhibitors, cycling to another JAK inhibitor is a more effective option than switching to a biological disease-modifying antirheumatic drug, according to data.
“Since the advent of biological disease-modifying anti-rheumatic drugs (bDMARDs), the treatment of RA has undergone a paradigm shift in the last 20 years,” Yusuke Miyazaki, of the University of Occupational and Environmental Health Japan, and colleagues wrote in RMD Open. “However, bDMARDs have some disadvantages. Their high molecular weight limits the route of administration to injection. Additionally, they can be associated with secondary failure due to the development of anti-drug antibodies. Therefore, Janus kinase inhibitors, which are low-molecular-weight compounds that can be orally administered, were developed.
“However, a subset of patients with RA demonstrated an inadequate response to JAK inhibitors and failed to exhibit significant improvements in disease activity,” they added. “Although several studies have focused on patients with [inadequate response to JAK inhibitors (JAKi-IR)] RA, they compared subsequent molecular-targeted drugs in terms of retention rate. It is unknown which molecular-targeted drug is more effective in patients with RA with JAKi-IR.”
To learn more about patients with an inadequate response to JAK inhibitors for RA, and which drugs may be appropriate for them, Miyazaki and colleagues analyzed RA registry data collected at their institution and multiple affiliated centers. The study included 434 patients treated with JAK inhibitors between August 2013 and April 2022, each of whom were followed for 26 weeks of treatment. A total of 138 patients (31.8%) demonstrated inadequate response to JAK inhibitors, meaning they either did not achieve low disease activity within 26 weeks of treatment or changed treatment due to inadequate response.
Patients who switched or cycled were followed for another 26 weeks, with the primary endpoint being the rates of remission, assessed using the Clinical Disease Activity Index, among switchers vs. cyclers. The disease trajectories of patients who switched drugs, and factors influencing those trajectories, were also assessed via growth mixture modelling.
Among patients with inadequate response, the 31 who cycled to another JAK inhibitor had a significantly higher remission rate (38.7%) than the 45 who switched to a biologic DMARD (2.2%), according to the researchers. Additionally, the researchers reported no significant difference in 26-week retention between switchers (75.6%) and cyclers (87.1%), nor was there a statistically significant difference in adverse events.
Meanwhile, the trajectory analysis split patients up into three groups, one of which was patients with moderate to high baseline disease activity who quickly improved after switching or cycling. According to a multivariable logistic regression, the “only factor” that was associated with inclusion in this group was having cycled to another JAK inhibitor (OR = 7.15; 95% CI, 2.21-23.1), the researchers wrote.
“This study raises the possibility that cycling to another [JAK inhibitor] contributes to more significant improvement than switching to bDMARDs in patients with RA with [inadequate response to JAK inhibitors],” Miyazaki and colleagues wrote. “Therefore, cycling to another [JAK inhibitor] may be the optimal option among molecular-targeted drugs for patients with RA and [inadequate response to JAK inhibitors].”
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