So Michelle, Vogrin Sara, Waibel Michaela, Kay Thomas W H, Wentworth John M
Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Diabetes Care. 2025 Aug 1;48(8):1370-1376. doi: 10.2337/dc25-0565.
Baricitinib preserves β-cell function in people with recently diagnosed type 1 diabetes. We aimed to determine whether simple routine clinical measures could be used to assess β-cell preservation and predict treatment response.
Measures of β-cell function derived from clinical and biochemical measures were calculated using data from the BAricitinib in Newly DIagnosed Type 1 diabetes (BANDIT) randomized trial of baricitinib in recent-onset type 1 diabetes. Measures that reported and predicted treatment efficacy were determined using linear regression and receiver operator characteristic analysis, respectively. Therapeutic predictors were validated using data from trials of rituximab, abatacept, and antithymocyte globulin.
Quantitative response score (QRS), fasting C-peptide, and model-estimated C-peptide (CPest) most reliably differentiated placebo-treated from baricitinib-treated participants at 24 and 48 weeks. The Beta2 score, derived from fasting glucose, C-peptide, HbA1c, and insulin dose at 12 weeks, was optimal for predicting QRS >0 following 1 year of treatment with baricitinib and the other immunotherapies (areas under receiver operator curve 0.864 and 0.765, respectively). A 6.2% decrease in the Beta2 score at week 12 predicted significant improvement in HbA1c (-0.6% or -6 mmol/mol) and insulin use (-0.26 units/kg/day) in combined data from the rituximab, abatacept, and antithymocyte globulin trials.
QRS, fasting C-peptide, and CPest could be used as more efficient, less burdensome primary outcome measures for future immunotherapy trials. The ability of the Beta2 score to predict treatment responses could facilitate adaptive trial designs and help guide treatment decisions in the clinic.
巴瑞替尼可保留新诊断1型糖尿病患者的β细胞功能。我们旨在确定是否可通过简单的常规临床指标来评估β细胞的保留情况并预测治疗反应。
利用巴瑞替尼治疗新诊断1型糖尿病（BANDIT）随机试验的数据，计算从临床和生化指标得出的β细胞功能指标。分别采用线性回归和受试者工作特征分析来确定报告和预测治疗效果的指标。使用利妥昔单抗、阿巴西普和抗胸腺细胞球蛋白试验的数据对治疗预测指标进行验证。
在24周和48周时，定量反应评分（QRS）、空腹C肽和模型估算的C肽（CPest）最能可靠地区分接受安慰剂治疗和接受巴瑞替尼治疗的参与者。由12周时的空腹血糖、C肽、糖化血红蛋白（HbA1c）和胰岛素剂量得出的Beta2评分，对于预测接受巴瑞替尼及其他免疫疗法治疗1年后QRS>0最为理想（受试者工作特征曲线下面积分别为0.864和0.765）。在利妥昔单抗、阿巴西普和抗胸腺细胞球蛋白试验的合并数据中，第12周时Beta2评分下降6.2%可预测糖化血红蛋白显著改善（-0.6%或-6 mmol/mol）以及胰岛素使用量减少（-0.26单位/千克/天）。
QRS、空腹C肽和CPest可作为未来免疫治疗试验中更高效、负担更小的主要结局指标。Beta2评分预测治疗反应的能力有助于适应性试验设计，并有助于指导临床治疗决策。
