Recombinant Soluble TNF-α Receptor Fusion Protein Therapy Reduces Insulin Resistance in Non-Diabetic Active Rheumatoid Arthritis Patients

Objective: Current evidence highlights a link between insulin resistance (IR) and disease activity in rheumatoid arthritis (RA), suggesting that insulin sensitivity can be improved by treating patients with TNF-α blockers. Although reduced IR has been shown in RA patients who receive monoclonal antibody treatment, the efficacy remains to be elucidated when using recombinant soluble receptor fusion proteins. In particular, etanercept (ETA) is capable of blocking lymphotoxin-α, a cytokine-related to IR-associated disease status. Methods: A prospective study was carried out in nondiabetic active RA patients receiving a 25-mg subcutaneous ETA injection twice weekly. Results: Thirty patients aged 31 to 73 years (50.9 ± 10.6), naïve to biological and targeted synthetic disease-modifying antirheumatic drugs with DAS28 scores of 5.17 to 7.49 (6.11 ± 0.66), were classified into high-IR and low-IR groups based on their baseline homeostatic model assessment (HOMA)-IR levels. No differences were found between the two groups in terms of age, sex, weight, body mass index, seropositivity, and medication profiles before the injection. After a 24-week therapeutic period, there were reduced HOMA-IR levels in all patients in the high-IR group (3.390 ± 0.636 to 2.234 ± 0.870, P < 0.001). A greater decrease in DAS28 values was found in patients with reduced IR than those without a reduction (2.54 ± 0.67 versus 1.46 ± 0.46, P = 0.006) in the low-IR group. Conclusion: We observed an improvement in insulin sensitivity in nondiabetic active RA patients following 24-week recombinant soluble TNF-α receptor fusion protein therapy.