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.

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.

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.  

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.

January 2024

In this two-round modified RAM study by Solitano, et al., the authors found that experts preferred to assess JAK inhibitor risk on a case-by-case basis across all specialties. Uncertainty remained on several clinical scenarios regarding the appropriate use of JAK inhibitors, however they remain an important therapy option for the treatment of IMIDs  and were deemed appropriate for patients with moderate risk profiles.

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Siderius, et al. found that secukinumab was associated with low spinal radiographic progression. Furthermore, bone-related outcomes and BTMs related to collagen resorption (sCTX, PINP) remained constant during the 2-year period, whereas the BTM related to mineralisation (BALP) decreased significantly.

Nationwide study involving 14 778 new users of targeted therapies with PsA found treatment persistence to be lower for women than men for TNFi and IL17i but not for IL-12/23i, IL-23i or JAK inhibition.

This monocentric, retrospective clinical study by Mastorino, et al. found that ixekizumab demonstrated efficacy an safety in patients with PsA and PsO for up to five years. Being a super-responder was significantly associated with a lower rate of discontinuation, while high BMI was associated with a lower achievement of more than one PSAI measure up to Week 104.

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