初治老年类风湿关节炎患者血清IL-33/ST2轴水平与达标治疗的关系及其预测价值

Relationship between serum IL-33/ST2 axis levels and treat-to-target outcomes in treatment-naïve elderly patients with rheumatoid arthritis and their predictive value

摘要:

目的 探讨初治老年类风湿关节炎（RA）患者血清白细胞介素-33（IL-33）/抑制肿瘤源性2（ST2）轴水平与达标治疗的关系，并评估其对治疗结果的预测效能。方法 选取2024年5月—2025年2月河南医药大学附属濮阳市人民医院的初治老年RA患者208例作为研究对象，根据治疗结局是否达标分为达标组和未达标组。治疗前检测患者血清IL-33及可溶性抑制肿瘤原性2（sST2）水平，并分析其与达标治疗结局的关系及预测价值。结果 未达标组与达标组性别构成、年龄、体质量指数、发病至就诊时间、用药情况、血沉、类风湿因子阳性率、抗环瓜氨酸肽抗体抗体阳性率、抗核抗体阳性率、C反应蛋白水平比较，差异均无统计学意义（P >0.05）。未达标组晨僵时间长于达标组（P <0.05），压痛关节数、肿胀关节数、视觉模拟评分法、28个关节疾病活动度（DAS28）评分、年龄调整查尔森指数（aCCI）评分等级均高于达标组（P <0.05），8条目Morisky用药依从性量表（MMAS-8）评分等级低于达标组（P <0.05）。未达标组IL-33、sST2水平均高于达标组（P <0.05）。多因素一般Logistic回归分析结果显示，基线DAS28评分高［O^R=1.523（95% CI：1.035，2.242）］，aCCI评分高［O^R=1.926（95% CI：1.120，3.312）］，IL-33水平高［O^R=1.117（95% CI：1.070，1.165）］和sST2水平高［O^R=1.249（95% CI：1.145，1.361）］是治疗未达标的独立危险因素，MMAS-8评分高［O^R=0.533（95% CI：0.335，0.849）］是治疗未达标的独立保护因素（P <0.05）。经受试者工作特征曲线分析，血清IL-33、sST2联合预测治疗未达标的曲线下面积为0.859，敏感性为80.0%（95% CI：0.722，0.878），特异性为78.6%（95% CI：0.706，0.866）。当血清IL-33>86.21 pg/mL，血清sST2>51.44 pg/mL时，治疗未达标风险随IL-33、sST2水平升高而增加。结论 初治老年RA患者血清IL-33、sST2水平是治疗未达标的独立危险因素，在预测达标指标结局中具有较高价值。

Abstract:

Objective To investigate the relationship between serum interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis levels and treat-to-target (T2T) outcomes in treatment-na?ve elderly patients with rheumatoid arthritis (RA), and to evaluate their predictive value for treatment response.Methods A total of 208 treatment-na?ve elderly RA patients admitted to Puyang People’s Hospital Affiliated to Henan Medical University between May 2024 and February 2025 were enrolled. Patients were divided into a T2T-achieved group and a non-achieved group according to treatment outcomes. Serum IL-33 and soluble ST2 (sST2) levels were measured before treatment. The association between IL-33/sST2 levels and treatment outcomes was analyzed, and their predictive value was evaluated.Results There were no significant differences between the T2T-achieved and non-achieved groups in sex distribution, age, body mass index, time from onset to consultation, medication use, ESR, RF positivity rate, anti-CCP antibody positivity rate, ANA positivity rate, or CRP levels (all P > 0.05). The non-achieved group had significantly longer morning stiffness duration (P < 0.05), higher tender joint count, swollen joint count, visual analogue scale (VAS) score, Disease Activity Score in 28 joints (DAS28) score, and age-adjusted Charlson comorbidity index (aCCI) score, and lower Morisky Medication Adherence Scale-8 (MMAS-8) score compared with the achieved group (all P < 0.05). Serum IL-33 and sST2 levels were significantly higher in the non-achieved group than in the achieved group (both P < 0.05). Multivariable logistic regression analysis showed that higher baseline DAS28 score [O^R = 1.523 (95% CI: 1.035, 2.242) ], higher aCCI score [O^R = 1.926 (95% CI: 1.120, 3.312) ], higher IL-33 level [O^R = 1.117 (95% CI: 1.070, 1.165) ], and higher sST2 level [O^R = 1.249 (95% CI: 1.145, 1.361) ] were independent risk factors for failure to achieve T2T, while higher MMAS-8 score [O^R = 0.533 (95% CI: 0.335, 0.849) ] was an independent protective factor (all P < 0.05). Receiver operating characteristic (ROC) curve analysis showed that the combined IL-33 and sST2 model yielded an area under the curve (AUC) of 0.859, with a sensitivity of 80.0% (95% CI: 0.722, 0.878) and specificity of 78.6% (95% CI: 0.706, 0.866). When IL-33 > 86.21 pg/mL and sST2 > 51.44 pg/mL, the risk of failing to achieve T2T increased with rising levels of IL-33 and sST2.Conclusion Serum IL-33 and sST2 levels are independent risk factors for failure to achieve T2T in treatment-na?ve elderly RA patients and have good predictive value for treatment outcomes.