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.

Effectiveness and Safety of Filgotinib in Rheumatoid Arthritis: A Real-life Multicentre Experience

Clin Exp Rheumatol 2024 doi 10.55563/clinexprheumatol/k78ug3 Epub ahead of print

This real-world observational study by La Barbera, et al. confirms that filgotinib is efficacious and safe for use in the management of RA. The authors also report that improvements in clinical and laboratory features were greater in bDMARD-naïve patients with RA.

This real-world study by Kim, et al. found no significant relationship between continued JAK inhibitor therapy in patients with IMIDs and the risk of subsequent recurrent HZ reactivation. They also found no significant difference in the number of days patients were treated for HZ in the JAK inhibitor continuation and discontinuation groups.

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.

Therapeutic intervention during the at-risk phase of RA with abatacept is feasible, with acceptable safety profiles. However, the efficacy of intermittent administration at multiple intervals remains to be assessed.

Charles-Schoeman, et al. carried out a descriptive integrated analysis on patients with RA that were treated in the SELECT programme, with up to 6.5 years of exposure. They concluded that upadacitinib 15 mg QD had an acceptable safety profile, but long-term upadacitinib treatment was associated with dose-dependent laboratory abnormalities.

This pooled analysis of four Phase 3 RCTs investigated the long-term efficacy baricitinib in patients with active RA who were MTX-IR, csDMARD-IR, or bDMARD-IR. They found that baricitinib demonstrated efficacy up to 6.5 years and was well tolerated.

Secukinumab efficacy regarding PROs and retention rate was comparable between axSpA and PsA patient groups when adjusted for confounders. Christiansen et al compared 6-, 12- and 24-month pain, fatigue, PGA, and HAQ PROs in axSpA and PsA patients treated with secukinumab, as well as 24-monthy retention rates in this real-world study.  

Kwon, et al. found that adalimumab exposure significantly reduced risk of incident and recurrent acute anterior uveitis (AAU) versus etanercept exposure and bDMARD non-exposure. Furthermore, exposure to etanercept significantly increased risk of incident and recurrent AAU versus bDMARD non-exposure.

Guselkumab treatment exhibited generally comparable and significant pharmacodynamic effects on IL-23/Th17–associated cytokines across participants with PsA who are biologic-naïve or have TNFi-IR. In coming to this conclusion, investigators assessed and compared immunologic differences and associations with clinical response to guselkumab in participants with active PsA who were biologic-naïve or TNFi-IR.