Kandeel et al. compared JAK inhibitors and TNF inhibitors in RA. JAK inhibitors demonstrated better functional improvement via HAQ-DI but showed insignificant difference in CDAI compared to TNF inhibitors; both classes had similar safety.

August 2024

Adami et al. conducted a retrospective analysis to evaluate the GC sparing effects of JAKi versus bDMARDs in rheumatoid arthritis patients. They found that JAKi therapy was associated with a significant reduction in GC dose compared with bDMARDs. This suggests that JAKi could be more effective in reducing long-term GC exposure in RA patients.

Keywords:

Su et al. conducted a comprehensive systematic review and network meta-analysis to assess the efficacy and safety of therapies for difficult-to-treat (D2T) RA. They found that tocilizumab and rituximab had superior efficacy and safety profiles, with 8mg every 4 weeks of tocilizumab identified as the optimal therapeutic dose.

July 2024

Patients classified as having a high neutrophil-to-lymphocyte ratio (NLR-High) who received filgotinib 200mg + MTX/csDMARDs exhibited consistently better responses after 12 weeks across clinical trials, clinical endpoints, and PROs, compared with NLR-Low patients. Taylor et al. analysed data from the 3 FINCH trials to investigate the potential association of baseline NLR with improved clinical response to filgotinib in MTX-naïve or MTX-experienced RA populations.

June 2024

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.