Arthritis Research & Therapy (Oct 2024)

Predictive biomarkers for low-dose IL-2 therapy efficacy in systemic lupus erythematosus: a clinical analysis

  • Ruiling Feng,
  • Xian Xiao,
  • Bo Huang,
  • Kai Zhang,
  • Xia Zhang,
  • Zhanguo Li,
  • Yuan Jia,
  • Jing He

DOI
https://doi.org/10.1186/s13075-024-03388-5
Journal volume & issue
Vol. 26, no. 1
pp. 1 – 11

Abstract

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Abstract Background Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. Methods We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Results Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. Conclusions These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

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