IL-6 receptor blockade does not slow beta cell loss in new-onset type 1 diabetes

BACKGROUND. IL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade of IL-6R with monoclonal antibody tocilizumab would slow loss of residual beta cell function in newly diagnosed type 1 diabetes patients. METHODS. We conducted a multicenter, randomized, placebo-controlled, double-blind trial with tocilizumab in new-onset type 1 diabetes. Participants were screened within 100 days of diagnosis. Eligible participants were randomized 2:1 to receive 7 monthly doses of tocilizumab or placebo. The primary outcome was the change from screening in the mean AUC of C-peptide collected duringthe first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6-17years). RESULTS. There was no statistical difference in the primary outcome between tocilizumab and placebo. Immunophenotyping showed reductions in downstream signaling of the IL-6R in T cells but no changes in CD4 memory subsets, Th17 cells, Tregs, or CD4(+) T effector cell resistance to Treg suppression. A DC subset decreased during therapy but regressed to baseline once therapy stopped. Tocilizumab was well tolerated. CONCLUSION. Tocilizumab reduced T cell IL-6R signaling but did not modulate CD4(+)T cell phenotypes or slow loss of residual beta cell function in newly diagnosed individuals with type 1 diabetes.

Automated summary

The study found that tocilizumab did not slow the loss of residual beta cell function in newly diagnosed type 1 diabetes patients, despite reducing T cell IL-6R signaling. Additionally, there were no changes observed in CD4(+)T cell phenotypes.