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

Adalimumab demonstrated superiority over placebo in reducing fatigue in RA at 12 and 52 weeks. Other interventions, which included golimumab, baricitinib, sarilumab, tocilizumab, and tofacitinib, also proved effective in reducing fatigue in patients with RA. Secukinumab also reduced fatigue by Week 52 in patients with SpA.

Tofacitinib treatment resulted in a significant simultaneous improvement of both metabolic and inflammatory parameters in RA patients with T2D. Due to increasing evidence for a link between RA, insulin resistance and T2D Di Muzio et al. investigated if consecutively recruited RA patients on tofacitinib therapy showed improvement in HOMA2-IR values over 6 months.

December 2023

Post hoc analysis of ORAL Surveillance data highlights that active disease in RA leads to higher risk of adverse medical events, regardless of medication used.

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This multicentre, retrospective study by Hayashi, et al. found no significant differences in efficacy and safety between tofacitinib, baricitinib, peficitinib and upadacitinib in patients with RA. Predictive factors for resistance to LDA achievement included baseline CRP and CDAI for tofacitinib and baseline glucocorticoid dose, baseline CDAI and number of previous b/tsDMARDs for baricitinib.

Rates of MACE and VTE events in patients with RA or PsA treated are consistent across 15 mg and 30 mg doses of upadacitinib, and comparable with active comparators adalimumab and MTX. Several risk factors were also identified for MACE and VTE events in patients with RA.

October 2023

Effets d'un traitement d'un an par le tofacitinib sur les biomarqueurs angiogéniques dans la polyarthrite rhumatoïde

Rheumatology (Oxford) 2023; 62(SI3):SI304–SI312 doi 10.1093/rheumatology/kead502

This study by Kerekes, et al. investigated the relationship between tofacitinib therapy, angiogenic biomarker levels, and vascular inflammation and function in RA patients. The authors found that tofacitinib treatment reduced the production of bFGF, PlGF and IL-6, which may inhibit synovial and aortic inflammation.

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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.

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.

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.