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

Carla J. Greenbaum, Elisavet Serti, Katharina Lambert, Lia J. Weiner, Sai Kanaparthi, Sandra Lord, Stephen E. Gitelman, Darrell M. Wilson, Jason L. Gaglia, Kurt J. Griffin, William E. Russell, Philip Raskin, Antoinette Moran, Steven M. Willi, Eva Tsalikian, Linda A. DiMeglio, Kevan C. Herold, Wayne V. Moore, Robin Goland, Mark HarrisMaria E. Craig, Desmond A. Schatz, David A. Baidal, Henry Rodriguez, Kristina M. Utzschneider, Hendrik J. Nel, Carol L. Soppe, Karen D. Boyle, Karen Cerosaletti, Lynette Keyes-Elstein, S. Alice Long, Ranjeny Thomas, James G. McNamara, Jane H. Buckner, Srinath Sanda

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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 β 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 during the first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6-17 years). 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 β cell function in newly diagnosed individuals with type 1 diabetes.

Original languageEnglish (US)
Article numbere150074
JournalJCI Insight
Volume6
Issue number21
DOIs
StatePublished - Nov 8 2021
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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