Baricitinib works by interfering with signaling pathways inside immune cells, to reduce inflammation and lower the immune system. It is part of a class of drugs called Janus kinase (JAK) inhibitors. JAK comes in two forms, JAK1 and JAK2, and Baricitinib targets both of them.
Baricitinib is not a new drug; it was first approved by the US Food and Drug Administration (FDA) in 2018. It is taken as a once-daily oral pill and used to treat other autoimmune diseases, such as rheumatoid arthritis and alopecia areata (an autoimmune form of hair loss). Because it has been in use for several years for other autoimmune conditions, its safety profile is well-understood.
Since the drug works on other autoimmune diseases, it seems reasonable to try it on type-1 diabetes. Also, there has been the usual success with nonobese diabetic mice, which are commonly used to test potential type-1 diabetes cures.
This Study
This study is a phase 2, double-blind, randomized, placebo-controlled trial. A total of 91 patients were enrolled, with 60 individuals assigned to receive Baricitinib and 31 to the placebo group. Participants were honeymooners, having been diagnosed within 100 days before the start of the treatment. They took one Baricitinib pill daily for almost a year.
The primary end point was the C-peptide level after a year. C-peptide is a substance released when the body produces insulin, serving as a reliable indicator of remaining beta-cell function.
Secondary endpoints included several practical measures of diabetes management, average daily insulin dose, A1c levels, and various metrics of glycemic control gathered from continuous glucose monitors. Tertiary end points included measuring things inside the immune system to see how Baricitinib affected them, especially what are called "effector memory CD8+ T cells".
The Results
The grey, placebo line shows the normal progression of T1D during the honeymoon phase. C-peptide generation falls steadily until it hits some small residual levels, where it stays constant. The amber, treatment line shows pretty much the opposite. C-peptide generation goes up, but then plateaus out. There is no doubt in my mind that this is a good outcome. Generating more C-peptide is good, and this is not just holding constant; at the beginning it is going up.
But there are two big questions here. First, is the difference important. Untreated people leveled out at a level around 0.43, but treated people leveled out at about 0.65 and that is still way below healthy. Second, this plateau was constant for the last 6 months of the study. and while the people were continuing to get Baricitinib. This tells me that at this dose, it is not just a matter of time to get more improvement.
Discussion
To me, the obvious next question is: will a higher dose show more improvement? This study shows improvement, but not enough to cure anyone, or even make much difference in treatment. Would a higher dose of Baricitinib have a bigger impact?
Another follow on question is: will earlier treatment prevent T1D? This is harder to study, and we will need to wait longer for the results. However, any treatment which preserves beta cells might prevent T1D, if given in the pre-honeymoon phase. And it is important to remember, this treatment did more than just preserve C-peptide production, it increased it.
The findings also support the concept that JAK inhibitors, as a class of drugs, may hold promise for treating type 1 diabetes. This could lead to further exploration of other JAK inhibitors in future clinical trials for this condition.
One other clinical trial testing JAK inhibitors is being run now. It is testing both abrocitnib and ritlecitinib. It started in 2023 and they hope to finish in 2026. It is recruiting in several sites in California, Other USA locations, Australia, and one in Canada. You can see details here:
(click on the grey space to see a map of study locations)
For More Information
- US Clinical Trials Registry (ClinicalTrials.gov): https://clinicaltrials.gov/study/NCT04774224
- Australian New Zealand Clinical Trials Registry for BANDIT study: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380252
- Study Web Site: https://www.trialnet.org/events-news/blog/study-finds-jak-inhibitor-baricitinib-slows-t1d
Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!
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