RA BRIDGE and RA BRANCH trials: Baricitinib and VTE Risk Save
Drs. Mrinalini Dey and Jon Giles discuss abstract LB0009 presented at EULAR 2026 in London
Transcription
Hello, my name is Malani Day and I am a rheumatology fellow here in London. I'm delighted to be reporting from EULAR 2026, also here in London. I am joined by Dr. John Giles from Cedars-Sinai Medical Center in California in the US, and we are going to be discussing the very last abstract to be presented at this congress, LB0000009, which is looking at the long-term safety data — really exciting stuff — looking at baricitinib versus TNF inhibitors in an enriched cohort. Specifically, we're going to be discussing results of VTE. So, Dr. Giles, thank you very much for joining me. Can you just give us a brief overview of the study?
So, this is a phase 4 safety trial. It was mandated by the FDA. The FDA had a lot of input into the design of the trial. The primary outcome was venous thromboembolic events, based on some signals from their randomized clinical trials, some issues about a class effect as well. There were more than 3,600 patients who were randomized to two doses of baricitinib — 2 mg, 4 mg — versus TNF inhibitors, which could be etanercept or adalimumab. The trial — there were two different trials put together: one was a standard global randomized clinical trial, and then the other was more of a pragmatic trial that was done in the US with less data collection, but still adjudicated events.
Okay. It was an events-based trial, so there were a certain number of venous thromboembolic events that were supposed to occur. It turned out that the trial was stopped early because if the trial had continued and they had accrued all those events, they still would not have been underneath the non-inferiority margin of 1.8 for the upper bound of the 95% confidence interval.
Okay. So there was numerically higher venous thromboembolic events in both of the arms of baricitinib, and it was basically equal for the 2 mg versus the 4 mg, but it was not statistically significantly higher — but certainly did not meet the criteria for non-inferiority.
Great. And I guess we're all looking at this through the lens of ORAL Surveillance and the warnings we've been receiving since that study came out. How do you think clinicians should view the data from RA-BRIDGE and RA-BRANCH now that we have this, for their clinical practice?
Well, I think it's important to note that this is really a very adventurous trial because the population was enriched for venous thromboembolic risk factors. So they could even have had a venous thromboembolic event in the past — now that was the minority of patients that had had those, but they are included in that group. And then the other risk factors like higher BMIs and older ages are included there. So I think this gives us an idea about what the actual risk is. And this is comparative risk too. So we're talking about the difference between TNF inhibitors and baricitinib. We're not talking about overall risk, and we're not talking about compared to not treating people with anything or treating them with other things.
So I think it gives us a good idea about what the actual numbers are. And subsequent analyses will be able to interpret what the risk factors are for those people who had the venous thromboembolic events. We'll be able to look at the other outcomes of secondary interest that were there, will be able to come up with numbers needed to harm and what the bounds on those are.
So I think there's more to come here, but I think when we're trying to put baricitinib as a single drug into context, and then also put the greater context of the risks of JAK inhibitors as a class, I think this is very, very important information — because we've been talking about ORAL Surveillance for about 5 years now, it has an impact on our practice as well. It potentially has an impact on our practice and allows us to kind of compare and contrast between the two different trials.
And then just speaking about the risk factors and the fact that it was an enriched cohort — able to comment on any of the other outcomes that we were looking at in ORAL Surveillance?
May well — so the interesting thing that's different from RA-BRIDGE and RA-BRANCH compared with ORAL Surveillance is that there's absolutely no signal for major adverse cardiovascular events or malignancies. And they're equivalently powered on those. They're not enriched for those, but they have basically the same number of patients and basically the same amount of follow-up time. So there's no real difference there. Now why that is, we don't know. We'll have to dig into that a little bit more. They're not enriched for those things, but people who have VTE are also enriched for risk factors for cardiovascular disease. So I think as we dig into the data a little bit more, we'll be able to compare and contrast, maybe doing some subgroup analyses with more of a
subgroup that looks like the inclusion criteria for oral surveillance and see if anything comes out of there. Um, it certainly does maybe lower the concern about those — whether that's a class effect or it's a drug specific effect, you know, we don't know. Um, remember that uh oral surveillance included a standard dose and a double dose. Yes. Um, and this includes a half dose and a standard dose. So, that could be part of what we're seeing too. And a different target as well. And a different target. Yes. Yeah. Um, so really not able to comment maybe on the whole class of how we use JAKs in general. Um, so interpret with caution maybe at this point. Interpret with caution I think.
And it really shows that, you know, these are two of the largest clinical trials that have ever been done in RA. Yeah. And we still have uncertainty about, you know, what they mean. Um, and then when we look over into other clinical trials that have, you know, a few hundred patients, you know, it just makes us realize, especially for safety, that safety outcomes really require big numbers of patients and some of them that we're not able to actually get to.
Okay, great. Well, thank you for taking us through that study. Um, so if you want to catch up on that study, it is the very last abstract in the Congress. Um, thank you very much for joining us here on RheumNow. Uh, do follow along for further coverage.
So, this is a phase 4 safety trial. It was mandated by the FDA. The FDA had a lot of input into the design of the trial. The primary outcome was venous thromboembolic events, based on some signals from their randomized clinical trials, some issues about a class effect as well. There were more than 3,600 patients who were randomized to two doses of baricitinib — 2 mg, 4 mg — versus TNF inhibitors, which could be etanercept or adalimumab. The trial — there were two different trials put together: one was a standard global randomized clinical trial, and then the other was more of a pragmatic trial that was done in the US with less data collection, but still adjudicated events.
Okay. It was an events-based trial, so there were a certain number of venous thromboembolic events that were supposed to occur. It turned out that the trial was stopped early because if the trial had continued and they had accrued all those events, they still would not have been underneath the non-inferiority margin of 1.8 for the upper bound of the 95% confidence interval.
Okay. So there was numerically higher venous thromboembolic events in both of the arms of baricitinib, and it was basically equal for the 2 mg versus the 4 mg, but it was not statistically significantly higher — but certainly did not meet the criteria for non-inferiority.
Great. And I guess we're all looking at this through the lens of ORAL Surveillance and the warnings we've been receiving since that study came out. How do you think clinicians should view the data from RA-BRIDGE and RA-BRANCH now that we have this, for their clinical practice?
Well, I think it's important to note that this is really a very adventurous trial because the population was enriched for venous thromboembolic risk factors. So they could even have had a venous thromboembolic event in the past — now that was the minority of patients that had had those, but they are included in that group. And then the other risk factors like higher BMIs and older ages are included there. So I think this gives us an idea about what the actual risk is. And this is comparative risk too. So we're talking about the difference between TNF inhibitors and baricitinib. We're not talking about overall risk, and we're not talking about compared to not treating people with anything or treating them with other things.
So I think it gives us a good idea about what the actual numbers are. And subsequent analyses will be able to interpret what the risk factors are for those people who had the venous thromboembolic events. We'll be able to look at the other outcomes of secondary interest that were there, will be able to come up with numbers needed to harm and what the bounds on those are.
So I think there's more to come here, but I think when we're trying to put baricitinib as a single drug into context, and then also put the greater context of the risks of JAK inhibitors as a class, I think this is very, very important information — because we've been talking about ORAL Surveillance for about 5 years now, it has an impact on our practice as well. It potentially has an impact on our practice and allows us to kind of compare and contrast between the two different trials.
And then just speaking about the risk factors and the fact that it was an enriched cohort — able to comment on any of the other outcomes that we were looking at in ORAL Surveillance?
May well — so the interesting thing that's different from RA-BRIDGE and RA-BRANCH compared with ORAL Surveillance is that there's absolutely no signal for major adverse cardiovascular events or malignancies. And they're equivalently powered on those. They're not enriched for those, but they have basically the same number of patients and basically the same amount of follow-up time. So there's no real difference there. Now why that is, we don't know. We'll have to dig into that a little bit more. They're not enriched for those things, but people who have VTE are also enriched for risk factors for cardiovascular disease. So I think as we dig into the data a little bit more, we'll be able to compare and contrast, maybe doing some subgroup analyses with more of a
subgroup that looks like the inclusion criteria for oral surveillance and see if anything comes out of there. Um, it certainly does maybe lower the concern about those — whether that's a class effect or it's a drug specific effect, you know, we don't know. Um, remember that uh oral surveillance included a standard dose and a double dose. Yes. Um, and this includes a half dose and a standard dose. So, that could be part of what we're seeing too. And a different target as well. And a different target. Yes. Yeah. Um, so really not able to comment maybe on the whole class of how we use JAKs in general. Um, so interpret with caution maybe at this point. Interpret with caution I think.
And it really shows that, you know, these are two of the largest clinical trials that have ever been done in RA. Yeah. And we still have uncertainty about, you know, what they mean. Um, and then when we look over into other clinical trials that have, you know, a few hundred patients, you know, it just makes us realize, especially for safety, that safety outcomes really require big numbers of patients and some of them that we're not able to actually get to.
Okay, great. Well, thank you for taking us through that study. Um, so if you want to catch up on that study, it is the very last abstract in the Congress. Um, thank you very much for joining us here on RheumNow. Uh, do follow along for further coverage.
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