February 2024

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.

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Continued JAK Inhibitor Treatment on the Risk of Recurrent Herpes Zoster Reactivation in Patients with Immune-mediated Inflammatory Diseases: A Nationwide Population-based Study in South Korea

Semin Arthritis Rheum 2024 doi 10.1016/j.semarthrit.2024.152362 Epub ahead of print

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.

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The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof‑of‑concept, open, prospective, clinical study

https://pubmed.ncbi.nlm.nih.gov/38178250/

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.

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January 2024

Cardiovascular Safety of Janus Kinase Inhibitor Therapy in a Multi-ethnic Population

Musculoskeletal Care 2023 doi 10.1002/msc.1853 Epub ahead of print

This study by Sunmboye, et al. investigated the relationship between CV event incidence and age in a multi-ethnic population that received JAK inhibitor therapy. They concluded that JAK inhibitor therapy was generally safe in a multi-ethnic population with a large age range, but they did find a statistically significant but numerically small positive correlation between age and CV incidence

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Filgotinib Demonstrates Efficacy in Rheumatoid Arthritis Independent of Smoking Status: Post Hoc Analysis of Phase 3 Trials and Claims-Based Analysis)

Rheumatol Ther 2023;11(1):177–189 doi 10.1007/s40744-023-00619-0

This post hoc analysis by Curtis, et al. found that current and former smokers were more likely to switch from an anti-TNF bDMARD to a different bDMARD or JAK inhibitor in comparison to non-smokers. They also found that DAS28(CRP) ≤3.2 achievement was significantly higher after filgotinib therapy regardless of smoking status in MTX-IR, bDMARD-IR, and MTX-naïve patients.

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Implementation of Regulatory Guidance for JAK Inhibitors Use in Patients with Immune-Mediated Inflammatory Diseases: An International Appropriateness Study

Autoimmun Rev. 2023;23(3):103504 doi: 10.1016/j.autrev.2023.103504 Epub ahead of print

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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Influence of Sex on the Persistence of Different Classes of Targeted Therapies for Psoriatic Arthritis: A Cohort Study of 14 778 Patients from the French Health Insurance Database (SNDS)

RMD Open. 2023;9(4):e003570 doi: 10.1136/rmdopen-2023-003570

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.

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December 2023

Real-world Comparative Study of the Efficacy of Janus Kinase Inhibitors in Patients with Rheumatoid Arthritis: The ANSWER Cohort Study

Rheumatology 2023 doi 10.1093/rheumatology/kead543

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.

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MACE and VTE across Upadacitinib Clinical Trial Programmes in Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis

RMD Open 2023; 9(4):e003392 doi 10.1136/rmdopen-2023-003392

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.

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Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis

Rheumatol Ther 2023;11(1):97–112 doi 10.1007/s40744-023-00621-6

Rates of malignancy were similar between upadacitinib, adalimumab, and MTX. They were also consistent across RA, PsA, AS and nr-axSpA. A dose-dependent increased rate of NMSC was observed with upadacitinib in RA. For RA and PsA, being older (≥65 years) and male was associated with
an increased risk of malignancy excluding NMSC.

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