Switching to biological DMARDs versus cycling among JAK inhibitors in patients with rheumatoid arthritis and with inadequate response to JAK inhibitors: from FIRST registry.

This study aimed to identify characteristics of patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi-IR) and evaluate the efficacy and safety of subsequent treatments. This study included 434 patients with RA who started JAKi treatment. JAKi-IR patients were those who switched to another drug due to inadequate response or did not reach low disease activity within 26 weeks of beginning JAKi. The efficacy and safety of switched biological disease-modifying anti-rheumatic drugs (bDMARDs) or cycled targeted synthetic disease-modifying anti-rheumatic drugs were analysed 26 weeks after switching treatment in JAKi-IR patients. Patients with JAKi-IR RA accounted for 31.8% (n=138/434). Multiple logistic regression identified factors contributing to JAKi-IR, such as the prior use of multiple ineffective bDMARDs and suboptimal JAKi dosing. There were no differences in patient background when comparing patients with RA with JAKi-IR who cycled to another JAKi (n=31) versus those who switched to bDMARDs (n=45). Among those cycling to another JAKi, the Clinical Disease Activity Index (CDAI) scores improved by week 26, with higher remission rates, while retention and adverse events remained similar. Trajectory analysis identified three CDAI response patterns, with the 'treatment response' group showing rapid and sustained improvement when cycling to another JAKi. Multiple logistic regression in this group identified another JAKi cycle as the critical factor for the treatment response. Cycling JAKis is more effective than switching to bDMARDs in JAKi-IR RA, with no differences in safety or retention. This study suggests that cycling to another JAKi may be appropriate for patients with RA with JAKi-IR.

Miyazaki Y ，Nakayamada S ，Tanaka H ，Hanami K ，Fukuyo S ，Kubo S ，Yamaguchi A ，Miyagawa I ，Satoh-Kanda Y ，Todoroki Y ，Inoue Y ，Ueno M ，Tanaka Y ... -  《-》

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

The 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. This 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. 365 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. After 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.

Pombo-Suarez M ，Sanchez-Piedra C ，Gómez-Reino J ，Lauper K ，Mongin D ，Iannone F ，Pavelka K ，Nordström DC ，Inanc N ，Codreanu C ，Hyrich KL ，Choquette D ，Strangfeld A ，Leeb BF ，Rotar Z ，Rodrigues A ，Kristianslund EK ，Kvien TK ，Elkayam O ，Lukina G ，Bergstra SA ，Finckh A ，Courvoisier DS ... -  《-》

Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs.

Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.

Opdam MAA ，Broeder ND ，van den Bemt BJF ，Mulder K ，van de Wiel KM ，van Ballegooijen H ，van Crevel R ，den Broeder AA ... -  《-》

Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study.

Yoshida S ，Miyata M ，Suzuki E ，Kanno T ，Sumichika Y ，Saito K ，Matsumoto H ，Temmoku J ，Fujita Y ，Matsuoka N ，Asano T ，Sato S ，Migita K ... -  《Frontiers in Immunology》

Comparison of anti-IL-6 receptor and JAK inhibitors in patients with rheumatoid arthritis from the real-world practice FIRST study.

Miyazaki Y ，Nakayamada S ，Tanaka H ，Hanami K ，Fukuyo S ，Kubo S ，Miyagawa I ，Yamaguchi A ，Todoroki Y ，Inoue Y ，Ueno M ，Tanaka Y ... -  《-》