Baricitinib (trade name Olumiant) is a drug which targets the immune system, and is already approved for Rheumatoid Arthritis (since 2018) and Alopecia Areata (since 2022). Since these two diseases are both autoimmune diseases, like T1D, it makes sense that this drug would be tried for T1D as well. This drug is called a JAK inhibitor, and it blocks both JAK variants: JAK1 and JAK2. JAK inhibitors have been an active area of research because of some case studies where they seem to impact T1D when people took them for other conditions. I blogged on this once before:
https://cureresearch4type1diabetes.blogspot.com/2021/02/ruxolitinib-case-study.html
About This Study
People were recruited in their honeymoon phase, within 100 days of diagnosis. A total of 91 people participated, 60 got treatment and 31 were in a control group. The age range was 10 to 30, and about half were under 18 and half over. They took a 4mg pill of Baricitinib (or placebo) once a day for 48 weeks. The study was blinded for both participants and researchers.
The study was funded by JDRF and JDRF Australia.
Results
The key results for me are C-Peptide numbers, which are shown in the graph below. The treated group (Baricitinib) actually rose in C-Peptide generation, going from 0.6 to 0.65, a rise of 8%. That is not huge, but it is in the right direction, and it is not just "preserving" beta cells, it is growing them.
Discussion
For me, these are good results in a first-in-T1D clinical trial, but it definitely needs follow-on work. At this point, I think it is pretty clear that any treatment that helps C-Peptide numbers in the honeymoon phase should be tried in at-risk people. To use TrialNet terminology, if it works in stage 3, it should work better in stage 2.
You can see the confidence bars in the image above, they are the little horizontal bars above and below the measurements, and the same color. Confidence bars represent the uncertainty in measurement, and the uncertainty in averaging a small number of data points. We talk about an average as though it were one, exact number. But an average is a statistical combination of many numbers. Each one of those numbers has a measurement error (was it really 0.6 or was it 0.62 or maybe 0.59)? Hopefully those errors cancel out as we measure more data points, but it is possible they combine to get worse. Also, the average of a small number of data points might be different than the average of a large number of data points even if they are measuring the same thing. Researchers summarize these uncertainties on their graphs with confidence bars. Two data points within each other's confidence bars might be the same, even if they appear different.
If you look at the diagram, the placebo and treatment are
within confidence interval of each other, until the last measure. Even then, the treatment group is just barely outside the confidence interval of the placebo. (And the placebo is clearly inside the confidence interval of the treatment.) All this means, to me, that a bigger study is needed to get a strong signal. I'm hoping that would also lead to more data on how much beta cell growth there is.
Finally, it is important to remember that, although Baricitinib is approved for use already, it comes with black box warnings, which are the most serious warnings that the FDA has. These need to be considered before off-label use is considered, and right now, using Baricitinib on people with T1D is off label.
There are two other JAK inhibitors approved for use in the US: Tofacitinib (sold as Xeljanz) and Upadacitinib (sold as Rinvoq).
JAK inhibitors are very different medicines than Tzield (Teplizumab), or Diamyd, or Verapamil, so it is entirely possible that two or more of these treatments could be used together in the future.
Trialnet is running a clinical trial on JAK inhibitors (Abrocitinib and Ritlecitinib) which I will blog on in the future. It is enrolling people between 12 and 35 year olds during the first 100 days of their honeymoon period. You can read more about it here: https://trialnet.org/our-research/newly-diagnosed-t1d/jakpot-t1d
News Coverage: https://www.medicalnewstoday.com/articles/rheumatoid-arthritis-drug-shows-promise-as-type-1-diabetes-treatment
Journal Article: https://www.nejm.org/doi/full/10.1056/NEJMoa2306691
Clinical Trial Registry: https://www.clinicaltrials.gov/study/NCT04774224
Wikipedia: https://en.wikipedia.org/wiki/Baricitinib
A Note About Naming Drugs
In the medical world, it is common to capitalize the name brand of drugs, like Olumiant, but not capitalize the generic names for drugs, like baricitinib. I have never understood this. To me, they are both proper names of specific things, and both should be capitalized. Therefore, I do capitalize both.
1 comment:
It is also terribly expensive. It is unlikely that in its present form it might be far to expensive for the minor outcome. Also in the US it is largely not prescribed because the manufacturer is not allowed to have the medication prescribed in the two pill pill dose that is used all across the world except the US. Still it is in the right direction and that is seriously good.
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