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.

December 2023

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.

November 2023

This study by Meissner, et al. estimated the effects of JAKi, TNFi, bDMARDs and csDMARDs on the risk of MACE in RA patients. The authors found no significant difference in MACE risk by treatment group, even among patients at increased CV risk.

Keywords:

Risco de Eventos Cardiovasculares Adversos Maiores em Distúrbios Inflamatórios Imunomediados com Biológicos e Moléculas Pequenas: Meta-análise em rede

Clin Gastroenterol Hepatol. 2023 Oct 9:S1542-3565(23)00767-X doi 10.1016/j.cgh.2023.09.033 Epub ahead of print

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.

September 2023

This meta-analysis by Wei, et al. found that JAKi therapy was not associated with a higher risk of MACE than treatment with adalimumab, abatacept, or placebo. However, a higher incidence of all-cause mortality was observed with tofacitinib treatment than with adalimumab treatment.

August 2023

High paraoxonase activity is associated with a significantly reduced risk of MACE and non-NMSC malignancies in white/European RA patients. The PON1 Q192R RR genotype had a significantly greater association with paraoxonase versus the QQ genotype, but had no significant association with MACE or non-NMSC malignancies.

March 2023

Baseline 10-year atherosclerotic cardiovascular disease risk and metabolic syndrome are potentially associated with the incidence of both MACE and malignancies in patients receiving TOFA in the PsA and PsO clinical trial programs. This post hoc analysis aimed to examine the baseline CV disease risk and its association with the occurrence of MACE and malignancies in TOFA-treated patients with PsA and PsO.

MACEs were observed in patients newly receiving compensation from the Long-term Illness Scheme for AS. The objective of this study was to describe the incidence of MACEs in French patients newly benefiting from the French LTI for AS. The study also sought to evaluate the effect of various treatments on the risk of MACE occurrence.

Analysis of pooled data from the baricitinib clinical development programmes finds a low incidence rate of MACE, myocardial infarction, lung cancer, VTE, and overall mortality in patients <65 years without risk factors.

February 2023

Data suggest that an important difference between P123LTE and ORAL Surveillance was the proportion of patients with a history of atherosclerotic CV disease (ASCVD).