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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This study by Bergman, et al. showed that RA patients are significantly more likely to adhere to upadacitinib within the first 12 months of prescription versus adalimumab, baricitinib, and tofacitinib. There was also a significantly lower risk of discontinuation for upadacitinib versus the other treatment prescriptions.

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.

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.

August 2023

The data gathered in this post-marketing surveillance study aligned with the previously established safety profile of tofacitinib, and reports were found to have consistent safety profiles in the treatment of both patient with PsA and RA. However, the results of this study should be interpreted considering the limitations of post-marketing surveillance studies.

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.

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 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.

This review by Taylor, et al. reviews the long-term safety and efficacy data for baricitinib. Results from several studies showed that baricitinib has greater efficacy and survival compared to TNF inhibitors, and that the rate of CDAI <10 for baricitinib-treated RA patients increased over the course of seven years. Data also showed that remission rates were higher in real-world evidence than in RCTs.