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.

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.

January 2024

In this two-round modified RAM study by Solitano, et al., the authors found that experts preferred to assess JAK inhibitor risk on a case-by-case basis across all specialties. Uncertainty remained on several clinical scenarios regarding the appropriate use of JAK inhibitors, however they remain an important therapy option for the treatment of IMIDs  and were deemed appropriate for patients with moderate risk profiles.

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November 2023

This retrospective inception cohort study investigated RA patients starting a new bDMARD or JAKi prescription between 01 August 2018 and 31 January 2022 from IQVIA’s Dutch Real-World Data Longitudinal Prescription database.

The results of this study show that anti-IL-12/23, JAK inhibitors, and anti-TNF-α were associated with slightly higher risk of MACE compared with placebo. The risk was no different between biologic treatments, and the magnitude of risk did not differ between IMID type.

October 2023

Janus Kinase Inhibitor—Tofacitinib Associated with Pemphigus: An Analysis of the FDA Adverse Event Reporting System Data

ExpExpert Opin Drug Saf. 2023;22(12):1317–1320 doi: 10.1080/14740338.2023.2248872

This study presents initial data suggesting an association between the use of JAK inhibitors and pemphigus. This research used the FAERS database to investigate connections between JAK inhibitor usage and the occurrence of pemphigus as an adverse event.

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September 2023

The results of a Bayesian network meta-analysis by Lee and Song showed that JAK inhibitors were more likely to achieve remission and LDA in DMARD-naive RA patients than MTX. However, there were no significant differences in remission rates nor LDA rates between the JAK inhibitors investigated.

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June 2023

The study demonstrated that obesity is a factor that could play a role in treatment decision-making in people living with inflammatory arthritis (IA). It appears that efficacy of TNFi is affected by patients’ weight/BMI in all forms of IA, while this is not the case for TCZ and ABA in RA, as well for IL-17 and IL-23 inhibitors in PsA.

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JAK Inhibitors and the Risk of Malignancy: A Meta-analysis Across Disease Indications

Ann Rheum Dis. 2023;82(8):1059–1067 doi: 10.1136/ard-2023-224049

The objective of this study was to estimate the association of JAKi with the incidence of malignancy, compared with placebo, TNFi and MTX.