Rheumatology and Immunology | Prof. Li Zhanguo's Team Reveals New Treatment Regimen for Rheumatoid Arthritis

2022-04-02

In March, 2022, Prof. Li Zhanguo’s team from the Department of Rheumatology and Immunology at Peking University People’s Hospital published an article entitled “Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial” in Signal Transduction and Targeted Therapy (IF: 18.187). The research demonstrated that Low-dose interleukin-2 (Ld-IL2) is potentially a therapeutic approach to further improve outcomes for patients with rheumatoid arthritis (RA).

Rheumatoid arthritis is a prevalent autoimmune disease characterized by progressive articular destruction and is notoriously difficult to treat with poor remission. Current treatment regimens mainly rely on conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic agents, which are associated with substantial adverse effects including liver damage, cytopenia, nausea, and various infections. Methotrexate (MTX) is the most widely accepted initial therapy, but it is not efficacious in a large proportion of patients. The potential adverse effects limit the use of MTX.

In this study, researchers conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of Ld-IL2 in patients with active RA. Patients were randomly assigned (1:1) to receive Ld-IL2, defined as a dose of 1 million IU,placebo in a 12-week trial with a 12-week follow-up. Three cycles of Ld-IL2placebo were administered subcutaneously every other day for 2 weeks (a total of 7 doses), followed by a 2-week break. All patients received a stable dose of methotrexate (MTX). The primary outcomes were the proportion of patients achieving the ACR20, DAS28-ESR <2.6, and the change from baseline in CDAISDAI at week 24. Secondary endpoints included other clinical responses and safety. The primary outcomes were achieved in the per-protocol population. The improvements from baseline in CDAI and SDAI were significantly greater across time points for the Ld-IL2 + MTX group (n = 17) than for the placebo+MTX group (n = 23) (P = 0.018 and P = 0.015, respectively). More patients achieved ACR20 response in the Ld-IL2 + MTX group than those in the placebo+MTX group at week 12 (70.6% vs 43.5%) and at week 24 (76.5% vs 56.5%) (P = 0.014). In addition, low Treg and high IL-21 were associated with good responses to Ld-IL2. Ld-IL-2 treatment was well-tolerated in this study.

This study provided the first clinical evidence that Ld-IL2 combined with MTX results in improvements in clinical and immunological responses of RA. The results demonstrated that Ld-IL2 is a novel and practical therapeutic approach in RA.

Dr. Zhang Xiaoying is the first author of this article. Prof. Li Zhanguo and Prof. He Jing are the co-corresponding authors. This study was supported by the Macao Science and Technology Fund, the National Natural Science Foundation of China and the Tsinghua University-Peking University Center for Life Sciences Fund.

Paper link: https://www.nature.com/articles/s41392-022-00887-2