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.

Keywords:

May 2024

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.

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.

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.

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.

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.

February 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.

Keywords:

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.

January 2024

Cardiovascular Safety of Janus Kinase Inhibitor Therapy in a Multi-ethnic Population

Musculoskeletal Care 2023 doi 10.1002/msc.1853 Epub ahead of print

This study by Sunmboye, et al. investigated the relationship between CV event incidence and age in a multi-ethnic population that received JAK inhibitor therapy. They concluded that JAK inhibitor therapy was generally safe in a multi-ethnic population with a large age range, but they did find a statistically significant but numerically small positive correlation between age and CV incidence

This post hoc analysis by Curtis, et al. found that current and former smokers were more likely to switch from an anti-TNF bDMARD to a different bDMARD or JAK inhibitor in comparison to non-smokers. They also found that DAS28(CRP) ≤3.2 achievement was significantly higher after filgotinib therapy regardless of smoking status in MTX-IR, bDMARD-IR, and MTX-naïve patients.