ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This phase 2, double-blind, placebo-controlled trial, randomized 91 people (10-30 years-old) diagnosed with type 1 diabetes (T1D) within the previous 100 days to receive either oral baricitinib (n=60) or placebo (n=31) for 48 weeks. Baricitinib was safe and preserved the capacity of β-cells to secrete insulin.

Baricitinib is a Janus kinase (JAK) inhibitor blocking cytokine signalling and is already an effective disease-modifying treatment for other autoimmune diseases, such as alopecia areata and rheumatoid arthritis (1,2). It is a plausible treatment for T1D because a key pathophysiological feature of T1D is the JAK-mediated destruction of β-cells by CD8+T cells. Preclinical data suggested JAK inhibitors might influence β-cell function by blocking this pathway (3).

BANDIT (Baricitinib in New-onset Type 1 Diabetes) was a phase 2 trial conducted in 4 Australian sites. It successfully achieved its primary endpoint, higher mixed-meal-stimulated C-peptide levels in the baricitinib vs. placebo group (0.65 vs. 0.43 nmol/L/min). Baricitinib slowed the decline in C-peptide known to occur after T1D diagnosis; in the placebo arm the decline was on average 30% vs. only 4% with baricitinib. Insulin requirements were lower in the group on baricitinib as well as glucose variability on continuous glucose monitoring. Of note, HbA1c was similar between groups, which could reflect a similar standard diabetes management through insulin therapy and glucose monitoring in both groups.

The study is limited by its relatively small sample size and Caucasian-predominant demographics. Nevertheless, it is the first trial demonstrating oral baricitinib as a safe and effective potential disease-modifying drug for T1D. Several immunotherapy trials have been conducted in people with T1D within the first 100 days from diagnosis, which is an important window to protect residual endogenous β-cell function. However, most other immunotherapy agents require intravenous or subcutaneous injections. Baracitinib has the advantage of its oral route of administration.

Next step, will be to confirm the trial findings in a larger, more diverse population with T1D, explore whether benefits persist over time, and assess whether some subgroups of T1D might benefit more from this treatment.

References: 1. Nash P, Kerschbaumer A, Dörner T, Dougados M, Fleischmann RM, Geissler K, et al. Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis. 2021;80(1):71-87.2. King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, et al. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022;386(18):1687-99.3. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;17(1):78.