1. In this randomized, double-blind, phase two trial, the use of golimumab led to more C-peptide production, indicative of improved endogenous function, compared to placebo in new type 1 diabetics.
2. Patients that received golimumab used less exogenous insulin compared to placebo.
Evidence Rating Level: 2 (Good)
Study Rundown: TNF-α has been implicated in the pathogenesis of type 1 diabetes. Golimumab is an antibody directed against TNF-α that has been approved for various other autoimmune diseases such as ulcerative colitis and rheumatoid arthritis. This was a randomized, double-blind, placebo-controlled trial of newly diagnosed type 1 diabetics treated with golimumab. The 4-hour C-peptide area under concentration-time curve (AUC) measured at 52 weeks was higher in the golimumab treated group compared to placebo which indicated a higher endogenous insulin production. At 52 weeks, there was a greater increase in insulin use in the placebo group. The trial was limited by the smaller number of participants. Furthermore, clinically relevant endpoints such as reductions in hypoglycemic events and quality of life were not investigated. Understandably given the short duration of the trial, diabetic complications such as retinopathy, neuropathy and nephropathy were not investigated but this will be important information to justify changes in practice in the future. Overall, the authors have demonstrated promising C-peptide responses with the use of golimumab which is indicative of improved beta-cell health but clinically relevant endpoints will be important investigational endpoints in further studies.
In-Depth [randomized controlled trial]: This was a phase two, double-blind, placebo-controlled, randomized trial examining the the use of golimumab to preserve beta cell function in 84 persons aged 6-21 who were newly diagnosed with type 1 diabetes (randomized within 100 days of diagnosis). The primary endpoint was assessed at 52 weeks. The mean 4-hour C-peptide AUC was higher in the golimumab group (0.64±0.42 vs. 0.43±0.39 pmol per milliliter; p <0.001). The least-squares mean change from baseline for insulin use was lower in the treatment group (0.07 U vs. 0.24 U per kilogram per day, p = 0.001) while HbA1c glycemic targets were similar (7.3±1.5% vs. 7.6±1.2%). The Hodges–Lehmann estimate of the median difference between treatment and placebo for fasting proinsulin to C-peptide was 0.124 (95% CI, 0.064 to 0.184), which indicated the treatment group may have had better beta-cell health. Infections were found in 71% of the treatment group, and 61% of the placebo group; a baseline decrease in neutrophil was higher in the treatment group (29% vs. 19%) where 4 patients had grade 3-4 neutropenia in the golimumab group. Hypoglycemia was higher in the golimumab group (23%) compared to the placebo (7%).
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