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.

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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August 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.

June 2023

Reinisch, et al. show that filgotinib treatment has no effect on semen parameters for men with active inflammatory diseases. This contrasts with pre-clinical studies that showed fertility issues in male animals.

January 2023

November 2022

Non-pharmacological interventions are important for any rheumatic disease, but especially axSpA, where they represent the cornerstone of treatment. The aim of this study was to produce a systematic literature review on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed.

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Post hoc analysis from the FINCH 1 study highlights filgotinib as a potential beneficial treatment option for patients with RA who have had inadequate response to MTX and have high risk of disease progression and poor prognosis.

June 2022

Maksymowych et al., assessed the effects of filgotinib on inflammatory and structural changes at various spinal locations, based on MRI measures in patients with active ankylosing spondylitis in the TORTUGA trial. Correlations between changes in the inflammation score and clinical outcomes were also evaluated.

Maksymowych et al., carried out a post-hoc analysis to assess the effect of filgotinib on MRI measures of structural change in the SI joint in patients with active AS in the TORTUGA trial. This study evaluated lesions using SPARCC SSS definitions for erosion, backfill, fat metaplasia and ankylosis by two independent scoring readers.

February 2022

Systematic review and network meta-analysis highlight that RA patients who receive recommended doses of the five approved JAK inhibitors (tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib) are likely to experience an increase in serum low- and high-density lipoprotein (LDL and HDL) levels.JAK inhibitors have been associated with alterations in levels of LDL and HDL cholesterol, which may lead to dyslipidaemia (an important risk factor for cardiovascular disease). However, the e...