A 2-year follow-up of the randomized, placebo-controlled BANDIT trial shows that stopping baricitinib leads to a loss of therapeutic benefit, supporting its evaluation in earlier stages of type 1 diabetes to determine whether it can prevent or delay clinical onset.
In 2023, researchers in Australia launched the pioneering BANDIT (Baricitinib in New Onset Type 1 Diabetes) trial, which showed that a daily dose of baricitinib, a medication already used to treat rheumatoid arthritis and alopecia, could help newly diagnosed patients with type 1 diabetes (T1D). The study found that the drug was able to protect the body’s own insulin production and slow the progression of the disease.
The latest update from the blinded BANDIT trial, presented at this year’s Annual Meeting of The European Association for the Study of Diabetes (EASD) in Vienna, shows what happened after treatment was withdrawn.
Once participants stopped taking baricitinib, their condition worsened. They produced less insulin and experienced more unstable blood sugar levels, with results that were not significantly different from those seen in the placebo group.
“Among the promising agents shown to preserve beta cell function in T1D, baricitinib stands out because it can be taken orally, is well tolerated, including by young children, and is clearly efficacious,” said author Dr. Michalea Waibel from St Vincent’s Institute of Medical Research, Fitzroy, Australia.
She added, “These latest data support our previous clinical trial data by showing that the therapeutic effect is lost when baricitinib is stopped and justify further trials to determine if treatment benefit can be sustained over many years on treatment and if treating earlier stages of disease can prevent or delay clinical diagnosis.”
Understanding Type 1 Diabetes and Baricitinib
T1D is caused by the immune system mistakenly attacking the insulin-producing cells in the pancreas. Over time, this leads to the need for lifelong insulin injections to manage blood sugar levels.
Baricitinib, a Janus kinase (JAK) inhibitor, works by blocking signals in the body that lead to overactivity of the immune system, and helps to protect the remaining insulin-producing cells in people who are newly diagnosed with T1D, thus delaying progression of full-blown symptoms. It is already prescribed to treat several autoimmune diseases, including rheumatoid arthritis, ulcerative colitis, and alopecia.
The BANDIT trial enrolled 91 people aged between 10 and 30 years old who had been diagnosed with T1D in the previous 100 days. Participants were either given a baricitinib pill (4mg) or a placebo, once daily for 48 weeks.
At the beginning of the trial and at weeks 12, 24, and 48, researchers measured participants’ C-peptide levels (a marker of insulin secretion) to find out how much insulin participants could make themselves. They also used continuous glucose monitoring and HbA1c (a marker of longer-term blood sugar levels) to assess the need for injected insulin and how well blood sugar levels were managed.
The findings revealed that taking a daily pill of baricitinib for 48 weeks preserved insulin-producing beta cell function, decreased blood glucose fluctuations, and reduced the need for insulin in people with newly diagnosed T1D. The researchers also found that baricitinib was safe, with no side effects attributed to the drug.
What Happened After Stopping Treatment
In this study, researchers report the findings from the off-drug follow-up period, with assessments done at weeks 72 and 96.
At 48 weeks the C-peptide level was 0.65 in the baricitinib group and 0.43 in the placebo group. After treatment was stopped, C-peptide levels fell to 0.49 in the baricitinib group and 0.36 in the placebo group at 72 weeks, and then to 0.37 and 0.26, respectively, at 96 weeks, demonstrating reduced insulin production.
The fall in insulin-producing beta cell function after baricitinib treatment was stopped resulted in the need for more insulin treatment, with insulin requirements at weeks 72 and 96 that were not significantly different between the groups.
Baricitinib cessation also led to a deterioration in glucose control, with differences in the time spent in the safe glucose range and blood glucose fluctuations between the groups in the first 48 weeks, no longer statistically significant at weeks 72 and 96.
Further analyses were unable to identify any characteristic at the start of the trial that predicted treatment response, including age, specific immune system genes known as human leukocyte antigens (HLA), body mass index (BMI), or number of autoantibodies. Moreover, drug adherence (at least 80% of study drug taken) did not distinguish responders from non-responders. Overall, around two-thirds of participants taking baricitinib met the criteria for response.
Notably, there was no additional safety concerns raised in the follow-up period.
“This is a really exciting step forward. For the first time, we have an oral disease-modifying treatment that can intervene early enough to allow people with T1D to be significantly less dependent on insulin treatment and provide time free from the demands of the disease’s daily management, and which could also lower rates of long-term complications,” said Dr. Waibel.
She added, “If we can identify people at high risk of developing type 1 diabetes with genetic tests and blood markers, they could be offered treatment even earlier to prevent the disease taking hold in the first place. We are hopeful that larger phase III trials with baricitinib are going to commence soon, in people with recently diagnosed T1D as well as in earlier stages to delay insulin dependence. If these trials are successful, the drug could be approved for T1D treatment within 5 years.”
Meeting: Annual Meeting of the European Association for the Study of Diabetes (EASD)
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