• N. Engl. J. Med. · Nov 2020

    Randomized Controlled Trial Multicenter Study

    Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes.

    • Teresa Quattrin, Michael J Haller, Andrea K Steck, Eric I Felner, Yinglei Li, Yichuan Xia, Jocelyn H Leu, Ramineh Zoka, Joseph A Hedrick, Mark R Rigby, Frank Vercruysse, and T1GER Study Investigators.
    • From the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, and Diabetes Center, John R. Oishei Children's Hospital, Buffalo, NY (T.Q.); the Department of Pediatrics, University of Florida, Gainesville (M.J.H.); the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora (A.K.S.); the Division of Pediatric Endocrinology, Emory University School of Medicine, Atlanta (E.I.F.); Janssen Research and Development, Spring House (Y.L., Y.X., J.H.L.) and Horsham (R.Z., J.A.H., M.R.R.) - both in Pennsylvania; and Janssen Research and Development, Beerse, Belgium (F.V.).
    • N. Engl. J. Med. 2020 Nov 19; 383 (21): 2007-2017.

    BackgroundType 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells. Golimumab is a human monoclonal antibody specific for tumor necrosis factor α that has already been approved for the treatment of several autoimmune conditions in adults and children. Whether golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes is unknown.MethodsIn this phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was endogenous insulin production, as assessed according to the area under the concentration-time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52. Secondary and additional end points included insulin use, the glycated hemoglobin level, the number of hypoglycemic events, the ratio of fasting proinsulin to C-peptide over time, and response profile.ResultsA total of 84 participants underwent randomization - 56 were assigned to the golimumab group and 28 to the placebo group. The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter, P<0.001). A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level. Insulin use was lower with golimumab than with placebo. A partial-remission response (defined as an insulin dose-adjusted glycated hemoglobin level score [calculated as the glycated hemoglobin level plus 4 times the insulin dose] of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group (difference, 36 percentage points; 95% CI, 22 to 55). The mean number of hypoglycemic events did not differ between the trial groups. Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 13 participants (23%) in the golimumab group and in 2 (7%) of those in the placebo group. Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies.ConclusionsAmong children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. (Funded by Janssen Research and Development; T1GER ClinicalTrials.gov number, NCT02846545.).Copyright © 2020 Massachusetts Medical Society.

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