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.

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.

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.

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.  

Effectiveness of Sequential Lines of Biologic and Targeted Small Molecule Drugs in Psoriatic Arthritis: A Systematic Review

Rheumatology (Oxford). 2024 Jan 18:keae006 doi: 10.1093/rheumatology/keae006 Epub ahead of print

The authors found that there is a reduction in effectiveness of lines of bDMARDs after first-line in PsA, with inadequate data to determine response to tsDMARDs.

Keywords:

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.

These recommendations from EULAR provide consensus and up-to-date guidance on fatigue management in people with I-RMDs, which includes advice regarding pharmacological and non-pharmacological interventions.

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.

Keywords:

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.