Beta cell function derived from routine clinical measures reports and predicts treatment response to immunotherapy in recent-onset type 1 diabetes.
Objective
Baricitinib preserves beta cell function in people with recently-diagnosed type 1 diabetes. We aimed to determine if simple routine clinical measures could be used to assess beta cell preservation and predict treatment response.
Research Designs and Method
Measures of beta cell function derived from clinical and biochemical measures were calculated using data from the BANDIT randomised 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 anti-thymocyte globulin.
Results
Quantitative response score (QRS), fasting C-peptide and model-estimated C-peptide (CPest) most reliably differentiated placebo- from baricitinib-treated participants at 24 and 48 weeks. Beta2 score, derived from fasting glucose, C-peptide, HbA1c and insulin dose at 12 weeks, was optimal for predicting QRS>0 following one 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 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 anti-thymocyte globulin trials.
Conclusions
QRS, fasting C-peptide and CPest could be used as more efficient, less burdensome primary outcome measures for future immunotherapy trials. The ability of Beta2 score to predict treatment responses could facilitate adaptive trial designs and help guide treatment decisions in the clinic.
