Hydroxychloroquine in Stage 1 Type 1 Diabetes
Objective: Innate immune responses may be involved in the earliest phases of type 1 diabetes.
Research Design and Methods: To test whether blocking innate immune cells modulated progression of the disease we randomized 273 individuals with stage 1 type 1 diabetes to treatment with hydroxychloroquine (n=183, 5 mg/kg/d to a maximum of 400 mg) or placebo (n=90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e. two or more islet autoantibodies with abnormal glucose tolerance).
Results: After median follow up of 23.3 months, the trial was stopped prematurely by the Data Safety Monitoring Board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic exams. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and a reduced titer of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (p=0.032).
Conclusions: We conclude that hydroxychloroquine does not delay the progression to stage 2 type 1 diabetes in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.