A disease-associated gene desert directs macrophage inflammation through ETS2

Nature 2024 doi: 10.1038/s41586-024-07501-1 Epub ahead of print

Stankey, et al. used functional genomics to show that the ETS2 gene is a central regulator of human inflammatory macrophages. They also found that ETS2 was disrupted by JAK inhibitors and MEK inhibitors, with multiple MEK inhibitors being shown to downregulate ETS2-target genes.

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Goldman, et al. conducted a pharmacovigilance study to evaluate the cardiovascular safety of JAK inhibitors in RA patients. The study demonstrated an increase in the reporting of VTE, stroke, and ischemic heart disease in patients treated with JAK inhibitor compared to bDMARDs, especially within the first year of treatment. This suggests a class effect of JAK inhibitors on cardiovascular risk, emphasising the need for ongoing surveillance and proactive cardiovascular risk management.

Burmester, et al. found that long-term filgotinib exposure was well tolerated in patients with moderate-to-severe active RA, with a stable rate of TEAEs over time. However, potential dose-dependent relationships for herpes zoster infections, malignancies and all-cause mortality were observed in patients aged ≥65 years, indicating the potential impact of age on the safety profile of Filgotinib. Therefore, some patients aged ≥65 years may benefit from the filgotinib 100 mg dose option.

May 2024

Crude gastrointestinal perforation (GIP) incidence rate was higher for the JAKi group compared with those receiving adalimumab, however rates of GIP did not differ between JAKi and adalimumab groups in the weighted and adjusted model. Hoisnard et al compared the risk of GIP in patients initiating treatment with JAKis or adalimumab among real-world patients with rheumatic disease.

Results of this analysis by Hernández-Cruz, et al. show that infections, herpes zoster and gastrointestinal AEs in patients with RA tended to be more frequent with JAKi treatment versus TNFi. They also found that treatment persistence was similar with JAKi and TNFi in patients with RA and axSpA, and only slightly higher for TNFi in patients with PsA.

April 2024

The 2023 EULAR recommendations provided an updated consensus on the pharmacological management of PsA with a new overarching principle and recommendation for 2023. Recent MOA safety data emphasised the importance of patient-specific benefit-risk profiling in JAKi therapy, and extra-musculoskeletal (MSK) manifestations related to PsA should be considered during drug selection.

The results of the meta-analysis show that TNFi, IL-17i, and JAK inhibitor treatments significantly improved sacroiliac joint SPARCC scores in patients with axSpA or AS at Weeks 12–16. However, there were no significant differences in mean improvement between the treatment groups.

March 2024

This study by Cho, et al. did not find any significant differences in remission rates in South Korean patients with RA that were treated with tofacitinib versus TNFi in a real-world setting. Remission rates were significantly higher for patients naïve to both JAKi and bDMARDs treated with tofacitinib versus TNFi.

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February 2024

Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician

Nat Rev Rheumatol 2024;20(2):101–115 DOI: 10.1038/s41584-023-01062-9

The observed benefit:risk ratio strongly favours JAKi use in the majority of patients, and HCPs should consider and adhere to guidance on high-risk patients where applicable. Szekanecz et al summarised the safety and efficacy of approved JAKis tofacitinib, baricitinib, upadacitinib, and filgotinib to aid in clinical decision making.

This real-world study by Kim, et al. found no significant relationship between continued JAK inhibitor therapy in patients with IMIDs and the risk of subsequent recurrent HZ reactivation. They also found no significant difference in the number of days patients were treated for HZ in the JAK inhibitor continuation and discontinuation groups.