Published online Jun 15, 2022. doi: 10.4239/wjd.v13.i6.454
Peer-review started: January 14, 2022
First decision: April 18, 2022
Revised: April 18, 2022
Accepted: May 28, 2022
Article in press: May 28, 2022
Published online: June 15, 2022
Processing time: 144 Days and 18.3 Hours
An increased risk of insulin resistance (IR) has been identified in rheumatoid arthritis (RA), a chronic inflammatory disorder with elevated levels of pathogenic cytokines. Biologics targeting proinflammatory cytokines can control the disease and improve insulin sensitivity in RA. Although Janus kinase (JAK) signaling can regulate cytokine receptors and participate in RA pathogenesis, it remains to be elucidated whether there is a reduction of IR in such patients under JAK inhibitor (JAKi) therapy.
To study the effect of JAKi treatment on the reduction of IR in RA patients with active disease.
A retrospective study was carried out from April 1, 2017 to March 31, 2021 in a population of non-diabetic patients with active RA who were undergoing tofacitinib (TOF) therapy with 5 mg twice-daily immediate-release formulation.
Fifty-six RA patients, aged 30 years to 75 years (mean ± SD: 52.3 ± 11.1) with disease activity score 28 values ranging from 4.54 to 7.37 (5.82 ± 0.74), were classified into high-IR (> 2.0) and low-IR (≤ 2.0) groups based on their baseline homeostatic model assessment (HOMA)-IR levels. They had no previous exposure to JAKi, and received TOF therapy for no less than 6 mo. In 30 patients who were naïve to biologics, after a 24-week therapeutic period, the high-IR group showed reduced HOMA-IR levels (3.331 ± 1.036 vs 2.292 ± 0.707, P < 0.001). In another 26 patients who were exposed to tumor necrosis factor-α or interleukin-6 blockers, the high-IR group, despite having achieved a decrease but with lower magnitude than in naïve patients, showed reduced HOMA-IR levels (2.924 ± 0.790 vs 2.545 ± 1.080, P = 0.018).
In this retrospective study, reduced IR was achieved in non-diabetic active RA patients following 24 wk of TOF therapy.
Core Tip: An increased risk of insulin resistance (IR) has been identified in rheumatoid arthritis (RA), a chronic inflammatory disorder with elevated levels of pathogenic cytokines. In addition to controlling RA activity, biologics targeting proinflammatory cytokines have been shown to reduce IR, while it remains to be elucidated whether Janus kinase inhibitor therapy can cause IR reduction in such patients. This retrospective study carried out in non-diabetic active RA patients classified into high-IR and low-IR groups before tofacitinib (TOF) therapy demonstrated reduced IR by 24 wk of TOF treatment in the active RA patients with high baseline IR status.