Differential Properties of Janus Kinase Inhibitors in the Treatment of Immune-mediated Inflammatory Diseases

Rheumatology (Oxford) 2023;63(2):298–308 doi 10.1093/rheumatology/kead448

JAKis differ in structure, which affects their inhibitory concentration for different JAKs.

This review by Taylor, et al. compares the pharmacological profiles of JAKis, including abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib, and upadacitinib.

Post-hoc analysis of SPIRIT-P1 and SPIRIT-P2 concludes that ixekizumab (IXE) is effective in improving axial symptoms in patients with active PsA presenting with axial manifestations.

Post-hoc analysis of two tofacitinib phase three studies concludes that tofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity.

Comparing the alignment of European national recommendations for patients with PsA and axSpA with EULAR and ASAS-EULAR treatment recommendations found that only a minority of national treatment recommendations were completely aligned.

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Phase IIb study of brepocitinib in patients with PsA concludes that treatment with brepocitinib 30 mg and 60 mg QD, was superior to placebo at reducing signs and symptoms of PsA and was well-tolerated over 52 weeks.

July 2023

This study by Tanaka, et al. shows that filgotinib reduces peripheral protein biomarkers associated with JAK/STAT signalling, inflammatory signalling, immune cell migration, and bone resorption in RA patients. Notably, filgotinib 200 mg significantly reduced IL-6, TNF, CXCL13 levels as early as Week 4.

High paraoxonase activity is associated with a significantly reduced risk of MACE and non-NMSC malignancies in white/European RA patients. The PON1 Q192R RR genotype had a significantly greater association with paraoxonase versus the QQ genotype, but had no significant association with MACE or non-NMSC malignancies.

This study concluded that, in r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Here, investigators aimed to determine how much of the effect of vertebral corner inflammation on the development of syndesmophytes is explained by vertebral corner fat deposition.

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Phase 3 trial of baricitinib demonstrates efficacy with acceptable safety profile in polyarticular and extended oligoarticular juvenile idiopathic arthritis, juvenile psoriatic arthritis and enthesitis-related arthritis.

Data from this open-label extension showed the efficacy of upadacitinib observed at 56 weeks was maintained through to 152 weeks in the treatment of patients with PsA. No cumulative adverse effects were observed, and no new safety signals were identified.