Therapeutic responses and predictors of low-dose interleukin-2 in systemic lupus erythematosus.

Miao Miao, Yimin Li, Dan Xu, Ruijun Zhang, Jing He, Xiaolin Sun, Zhanguo Li

Clinical and experimental rheumatology 2022 May

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Interleukin-2 (IL-2) is effective and well tolerated in patients with systemic lupus erythematosus (SLE). However, patient response to IL-2 therapy varies. Therefore, biomarkers are needed to efficiently identify patients who may respond well to IL-2 treatment. We investigated clinical and immunological biomarkers to predict low-dose IL-2 responses. A pooled post-hoc analysis was performed in SLE patients who received low-dose IL-2 treatment in two clinical trials. Factors predicting responses in clinical and T-cell subset changes were evaluated by logistic regression. Good response (GR) and poor response (PR) were defined according to whether patients achieved or did not achieve an SLE Responder Index-4 (SRI-4), respectively. A good response at 68% was achieved in patients with lower Treg, compared to 0% in patients with higher Treg. In comparison to PR, GR was more strongly associated with low Treg proportions at baseline (12.85±6.07% vs. 9.43±2.82%, p<0.01). There were more patients with skin rash in the GR group than in the PR group (68.75% vs. 30.77%, p=0.042). Multivariate analysis showed that low Treg proportions and skin rash presence were both independently associated with GR to low-dose IL-2 treatment. A nomogram to identify GR probability exhibited a clear discrimination (concordance index, 0.812; 95% confidence interval, 0.64-0.97). Based on the area under the receiver operating characteristic (ROC) curve (AUC) of 0.813, the specificity of a low regulatory T cells (Tregs) proportion (≤13.35%) plus skin rash to predict GR to IL-2 therapy was 100%, with a sensitivity of 68.75%. A low Treg proportion and skin rash indicate GR to low-dose IL-2 treatment in SLE patients.

Citation

Miao Miao, Yimin Li, Dan Xu, Ruijun Zhang, Jing He, Xiaolin Sun, Zhanguo Li. Therapeutic responses and predictors of low-dose interleukin-2 in systemic lupus erythematosus. Clinical and experimental rheumatology. 2022 May;40(5):867-871