A JAKi in GCA- Phase 3 Results Through 2 Years Save
A JAKi in GCA- Phase 3 Results Through 2 Years
Sponsored by AbbVie Medical Affairs + Health Impact
Transcription
Welcome to RheumNow. This podcast is sponsored and developed by AbbVie US Medical Affairs. My name is Anisha Dua. I'm a professor of medicine at Northwestern University and one of the vasculitis center there. And I am joined today by doctor Boone.
Welcome to the podcast. Can you introduce yourself for us?
Hello. My name is Ben Boone, and I'm a private practice rheumatologist based in Louisville, Kentucky.
Thanks, Doctor. Boone. I'm looking forward to our discussion on the two year outcomes from the Phase III SELECT GCA trial. This trial compared the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, with a twenty six week steroid taper to placebo with a fifty two week steroid taper for the treatment of patients with active giant cell arteritis. So the data we're discussing today was recently presented at ACR Convergence in 2025.
But before we get into the details, let's hear about the indications and limitations of use for upadacitinib in GCA.
Upadacitinib is a Janus kinase JAK inhibitor indicated for the treatment of adults with giant cell arteritis. Limitations of use for GCA. Upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants, such as azathioprine and cyclosporine.
Alright. With that, let's get into some of the new and exciting data. We know that there are so many difficulties in treating these complex patients with GCA. So I'm excited to talk about what we can do next. So, you know, we know that this disease has historically been very difficult to treat and that glucocorticoids have really been the first line treatment for GCA, but there's so many significant adverse effects, and there's a lack of steroid sparing treatment options.
We know that relapses have been a major problem with this disease, and they tend to occur during the first two years. But there's still a lot of uncertainty around long term disease management in GCA. And since glucocorticoids are used to treat flares, relapsing disease can lead to more glucocorticoid related side effects. There's the short term side effects of trouble sleeping, weight gain, mood changes, just feeling really jittery and uncomfortable to the longer term things like high blood pressure, osteoporotic hip fractures, new onset diabetes, glaucoma. It's such a long list, and every patient comes in with one of these other things.
So, I think it's an important area of study and so really clinically impactful. What are some of the issues that you encounter, Doctor. Boone, when you're treating patients with GCA?
Yeah, I mean, course, GCA is one of those diseases where a relatively high amount of steroids is a necessary evil. I tell my patients they're a blessing, but they're also a curse. And I, just like you said, I've experienced my own fair share of patients for whom steroids have had tremendously harmful impacts, having fractures, or inability to sleep, gaining lots of weight, having to start insulin for the first time. Steroid sparing or targeted therapy can certainly help us get off steroids more quickly, and stay off steroids more reliably long term. I think most rheumatologists have an inclination that one year of targeted therapy in GCA just isn't enough time, with most people likely using it a minimum of two or three years.
Some may even treat people indefinitely, as long as they can tolerate the treatment, especially for those who had some of those severe manifestations. I think we'll see today how the Select GCA two year data really validates this inclination we have to use targeted therapy for longer periods of time. But before we get there, let's remind ourselves of how things went with year one, or what we've called period one of the study. As we know, upadacitinib was recently approved for the treatment of GCA. Period one of select GCA, which was reviewed in a previous Rx update, was a fifty two week randomized double blinded study.
YUPPA fifteen plus a twenty six week glucocorticoid taper met the primary endpoint, demonstrating superior efficacy compared to placebo plus a fifty two week glucocorticoid taper, and attaining sustained remission at week fifty two. This was achieved at forty six percent in the YUPPA group versus twenty nine percent in the placebo group. Sustained remission here was defined as the absence of signs or symptoms of GCA from week twelve through week fifty two while adhering to the protocolized glucocorticoid taper. The question that period two of select GCA answers is, does continuing YUPA compared to withdrawing it after a year result in better efficacy outcomes for maintaining remission while also demonstrating a consistent safety profile. So, let's take a look now at how patients made their way from period one into period two.
Period two of select GCA was a blinded fifty two week extension period coming out of period one. Patients who attained remission in period one for at least twenty four consecutive weeks before that fifty two week visit were re randomized to either get on YUPA fifteen milligrams or switch to placebo in a two to one ratio. In this group, there were sixty eight patients in the YUPA fifteen milligram arm, which we'll call the continued YUPA group, and thirty five patients switched to placebo, which we'll call the withdrawn YUPA group. These two groups were assessed for efficacy comparing continuing YUPA fifteen versus withdrawing YUPA from week fifty two through week one 104. So, Doctor.
Dua, do you mind telling us a bit about the study population and efficacy results in period two of select GCA?
Okay, yes. So, for the patients that were originally in the YUPPA fifteen plus twenty six week taper group and continuing in period two, eighty seven percent of those in the continued YUPPA group and sixty nine percent of those in the withdrawn YUPPA group completed the trial. About three percent of patients in the continued UBA group had prior use of an IL-six inhibitor compared to eleven percent of those in the withdrawn UBA group. The demographics were generally similar across groups. Most of these patients were female.
The mean age was around 70 to 71 years old, and about three fourths of them had new onset disease. And so let's talk a little bit about some of the efficacy endpoints and starting off with one of the most important ones, which is remission. We know that remission is super important since GCA is a relapsing disease, and up to fifty to eighty percent of these patients relapse when glucocorticoids are tapered. So these patients in select GCA entered period two in a state of remission, but the question is how did they do over this next year? When we think about maintenance of remission from week 52 to week one zero four, we can just briefly review the definitions.
Remission was defined as the absence of GCA signs and symptoms and remaining glucocorticoid free from week fifty '2 to 01/2004. So sixty seven percent of patients in the continued UPDA group remained in remission through week one hundred four, compared to only twenty eight percent of patients in the withdrawn UPDA group. And when we shift over to complete remission from week fifty two to 01/2004, that's defined as remission, as we just discussed, with the additional normalization of ESR and CRP from week 52 to 01/2004. In this case, patients in the continued UPDA group were more likely to remain in complete remission through week one zero four compared to those in the withdrawn upa group, with fifty eight percent in the continued upa group maintaining complete remission compared to only fourteen percent of those in the withdrawn upa group. I think this really is pretty impressive and kind of aligns with what we thought would happen, but again, important to have the data to show us that really continuing patients on this maintenance of targeted therapy with upadacitinib really does improve their outcomes regardless of kind of which outcome you're looking at of remission or complete remission in the entire second year of their treatment.
So I think this is gonna be very important because, of course, when you withdraw YUPLA and if you fall out of remission, then, of course, that you're re exposing patients again to high doses of prednisone. So from a quality of life standpoint and from a re exposure to high doses of glucocorticoids, I think this is pretty compelling data that makes us understand the importance of continuing upadacitinib for longer than a year and at least throughout that second year.
Yeah. I agree for sure.
So in terms of outcomes, Select GC also looked at disease flare outcomes in period two. Doctor. Boone, can you tell us a little bit more about the time to disease flare and the relevance of that outcome in your practice?
Absolutely. Time to first disease flare was assessed in period two from week fifty two through week one hundred and four. And disease flare was defined as the recurrence of GCA signs or symptoms, or elevated ESR that required initiation of glucocorticoids. Patients continuing on YUPLA had a ninety percent reduction in risk of disease flare compared with those withdrawing YUPLA, with only fifteen percent in the continued group experiencing at least one flare compared to fifty nine percent in the withdrawn YUPA group. And if you look at the Kaplan Meier curve on the Rx update page for this data, you'll see that flare started occurring relatively soon after stopping YUPA in the withdrawn group.
And I really would encourage you to take a look at this. I think this is probably the striking visual that shows just how different these groups performed. Doctor. Dua, can you talk a little bit about in Select GCA how they fared in terms of cumulative glucocorticoid amounts?
So in period two of Select GCA, patients continuing YUPPA had lower median cumulative glucocorticoid exposure of zero milligrams. Zero. That's amazing. Compared to those withdrawing YUPPA who had a median cumulative glucocorticoid dose of over a thousand milligrams. And I know we've touched on this a little bit so far, but the implications of this lower glucocorticoid exposure is huge.
I mean, especially after that first, you know, year where they are exposed, so many of my patients are just terrified of having to be put back on steroids. So the implications of how little steroids or glucocorticoids were needed in the second year in patients who continued to use back is really important.
Agreed. Yeah. It's one of the most important things we can do is try to get steroids down. I mean, we're seeing this in various clinical trials, various disease states. Some of the trends is how little steroids can we use while achieving the same or better outcomes?
Yeah. Of course. And I think that leads us kinda nicely into safety. Right? Because we we're talking about the safety of these medications.
So in this second year, what is the safety in this population? We know that this is an elderly population, so it's important to discuss benefit risk equation, especially in this patient population. The key outcomes in terms of safety, they retract over about two years for the patients patients who took YUPPA fifteen and for those who received placebo and never took YUPPA. For patients on YUPPA, only side effects that happened while they were on YUPPA or within thirty days after stopping were counted. Overall, the safety profile of YUPPA in GCA was consistent with the profile in period one, and no new clinically significant safety risks were identified with the use of YUPPA for two years.
There were some higher rates of herpes zoster observed in those on YUPPA 15 compared to placebo, and that was 5.9 versus three point zero events per a 100 person years respectively. And, you know, in terms of the herpes zoster data, we know that this is something we are concerned about in elderly population in general, in those on glucocorticoids, and then also in those who are getting JAK inhibitors. So I think this really does sort of highlight the need to discuss vaccinations in our patients. Right? So we have to make sure we have good strategies in place or good alerts when we're in a busy clinical practice to try to make sure we're discussing vaccinations in our patient population.
Do you have any thoughts, Doctor. Buena?
Yeah. I mean, I think this reinforces our need to make sure our patients are getting vaccinated against zoster when they're going on JAK inhibitors. And now, it's not just zoster that we need to think about, but there's other adverse events we need to think about when it comes to JAK inhibitors, and so, let's talk about VTE and MACE. Rates of thromboembolic events were similar in those in the YUPA fifteen group compared to the placebo group with three point three versus three point zero people per one hundred person years experiencing a thromboembolic event, respectively. Looking at the major adverse cardiac events, there were no reports of MACE in the YUPA fifteen group, but there were two in the placebo group, and these both occurred during period one when people were on higher doses of steroids.
So, doctor Dua, how did these patients fare in terms of malignancy or serious infections?
Yeah. Again, really important questions in terms of things that come up in clinic a lot. So the rates of malignancy, excluding nonmelanomatous skin cancer, were similar between YUPPA fifteen and placebo, with one point nine versus one point five people per a 100 person years experiencing a malignancy, respectively. YUPPA fifteen had lower rates of serious infections compared to placebo with five point nine versus ten point five events per a 100 person years, respectively. And so, you know, in terms of how this impacts patients and their tolerability, these are important discussions to have with the patients.
Right? These are the kind of scary new concepts to them. So discussing these are the risks of clots, these are the risks of cancers, these are the risks of prolonged glucocorticoid exposure, these are all really important clinical conversations to have with our patients. But I think this data is really reassuring that in, you know, over a two year period, we really weren't seeing new safety signals in this continued UPPA arm. Doctor Boone, do you have any other thoughts on safety data that's come up here?
I know it's a a huge question that patients are always asking about.
Yeah, I like the way you talked about these sort of trade offs that we face. That's actually one of the things that I often tell my patients, especially when they have a disease that requires more intense therapy. Say there's no solutions, there's only trade offs, and so weighing these trade offs is super important. And it's tough with rare diseases to generate huge numbers of patients over a long period of time, but I think we have a good amount of patients here, and it's reassuring that we aren't seeing any obvious signals from many of these major adverse events compared to placebo with the exception of zoster.
Yeah. And patients are used to hearing the word, you know, steroids or prednisone, and they're not familiar necessarily with a lot of these other sort of targeted therapies. And so being able to really explain that even though you've heard about steroids before, it doesn't mean that it's safe and that there is actually an associated risk of infection is really important to be able to communicate that message and having the data behind it. Having this information is really critical in in terms of educating our patients. So I think those are all super important points.
And just to summarize what we know now from this period two data, the continued use of upadacitinib was associated with maintenance of remission, a lower likelihood of flares, and reduced cumulative glucocorticoid exposure in period two. And as we just talked about, no new safety risks were identified. I think, you know, this is a new mechanism of action that has been approved for this disease, and it's being increasingly used across practices. And I have patients on the treatment, and they ask me how long am I gonna be on it. And now we have good information that lets us know that, you know, if we stop it after that first, you know, year, there's a concern for flare that happens pretty quickly after stopping it.
And so what about you? What do you think?
Yeah. I agree. I mean, kinda similar themes here. We knew from the period one data and the New England Journal publication that YUPLA is an effective steroid sparing therapy for GCA. And while we had some reassuring safety data at the time, the one year time frame had us wondering whether over two years we would start to see some new signals of concern.
Especially, and as you said, this older population that has more comorbidities, and they're at higher risk for complications. So, this two year data really provides some reassurance to me. My biggest takeaway otherwise is just how impressive the sustained benefit of YUPPA was during period two. Eighty five percent of patients having no flares over a whole year is just a really compelling number to me, and probably impacts my desire to use YUPPA and GCA the most. This flare rate was also expressed by the continued use of YUPA reducing the flare rate by ninety percent compared to withdrawing YUPA.
We would probably have been pretty impressed if this number was about fifty percent reduction, but such a big relative reduction by ninety percent really speaks highly of the durability of response to this drug. We're talking about such a high stakes disease like GCA that many people need treatment for for several years. This durability of response is just so important to how I think about treating my patients.
Thank you for joining us to learn more about Select GCA. And listeners, if you would like to learn more about Select GCA period two, take some time to visit roomnow.com and view the therapeutic update on this data. And thank you, doctor Bundo. Was really fun talking with you about this.
Absolutely. Yeah. Glad to be here. This is great.
It is important to note that upadacitinib has a boxed warning for serious infections, mortality, malignancies, major adverse cardiovascular events, and thrombosis. Patients treated with upadacitinib are at an increased risk for developing serious infections that may lead to hospitalization or death. Malignancies have been observed in upadacitinib treated patients. In RA patients treated with another JAK inhibitor, a higher rate of lymphomas and lung cancers was observed when compared with TNF blockers. Non melanoma skin cancers have also been reported.
Periodic skin examinations are recommended in patients at increased risk, and patients should wear protective clothing and use sunscreen. Additionally, a higher rate of all cause mortality, including sudden cardiovascular death, as well as major adverse cardiovascular events, pulmonary embolism, and venous and arterial thrombosis, were observed with another JAK inhibitor compared with TNF blockers in RA patients 50 years of age and older with at least one cardiovascular risk factor. Thromboses have also been observed in upadacitinib treated patients. Avoid upadacitinib in patients at risk of thrombosis. Consider the individual patient's risks and benefits prior to initiating or continuing therapy.
The most common adverse reactions in GCA greater than or equal to five percent are upper respiratory tract infections, headache, fatigue, peripheral edema, cough, anemia, rash, herpes zoster, and nausea. Please also read the additional safety information within AbbVie's November 2025 Rx update on roomnow.com regarding hypersensitivity reactions, other serious adverse reactions, avoiding live vaccines and the importance of immunizations, and medication residue in stool. Review upadacitinib full prescribing information for additional information at www.rxabvi.com/pdf/rinvoke_pi.pdf.
Welcome to the podcast. Can you introduce yourself for us?
Hello. My name is Ben Boone, and I'm a private practice rheumatologist based in Louisville, Kentucky.
Thanks, Doctor. Boone. I'm looking forward to our discussion on the two year outcomes from the Phase III SELECT GCA trial. This trial compared the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, with a twenty six week steroid taper to placebo with a fifty two week steroid taper for the treatment of patients with active giant cell arteritis. So the data we're discussing today was recently presented at ACR Convergence in 2025.
But before we get into the details, let's hear about the indications and limitations of use for upadacitinib in GCA.
Upadacitinib is a Janus kinase JAK inhibitor indicated for the treatment of adults with giant cell arteritis. Limitations of use for GCA. Upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants, such as azathioprine and cyclosporine.
Alright. With that, let's get into some of the new and exciting data. We know that there are so many difficulties in treating these complex patients with GCA. So I'm excited to talk about what we can do next. So, you know, we know that this disease has historically been very difficult to treat and that glucocorticoids have really been the first line treatment for GCA, but there's so many significant adverse effects, and there's a lack of steroid sparing treatment options.
We know that relapses have been a major problem with this disease, and they tend to occur during the first two years. But there's still a lot of uncertainty around long term disease management in GCA. And since glucocorticoids are used to treat flares, relapsing disease can lead to more glucocorticoid related side effects. There's the short term side effects of trouble sleeping, weight gain, mood changes, just feeling really jittery and uncomfortable to the longer term things like high blood pressure, osteoporotic hip fractures, new onset diabetes, glaucoma. It's such a long list, and every patient comes in with one of these other things.
So, I think it's an important area of study and so really clinically impactful. What are some of the issues that you encounter, Doctor. Boone, when you're treating patients with GCA?
Yeah, I mean, course, GCA is one of those diseases where a relatively high amount of steroids is a necessary evil. I tell my patients they're a blessing, but they're also a curse. And I, just like you said, I've experienced my own fair share of patients for whom steroids have had tremendously harmful impacts, having fractures, or inability to sleep, gaining lots of weight, having to start insulin for the first time. Steroid sparing or targeted therapy can certainly help us get off steroids more quickly, and stay off steroids more reliably long term. I think most rheumatologists have an inclination that one year of targeted therapy in GCA just isn't enough time, with most people likely using it a minimum of two or three years.
Some may even treat people indefinitely, as long as they can tolerate the treatment, especially for those who had some of those severe manifestations. I think we'll see today how the Select GCA two year data really validates this inclination we have to use targeted therapy for longer periods of time. But before we get there, let's remind ourselves of how things went with year one, or what we've called period one of the study. As we know, upadacitinib was recently approved for the treatment of GCA. Period one of select GCA, which was reviewed in a previous Rx update, was a fifty two week randomized double blinded study.
YUPPA fifteen plus a twenty six week glucocorticoid taper met the primary endpoint, demonstrating superior efficacy compared to placebo plus a fifty two week glucocorticoid taper, and attaining sustained remission at week fifty two. This was achieved at forty six percent in the YUPPA group versus twenty nine percent in the placebo group. Sustained remission here was defined as the absence of signs or symptoms of GCA from week twelve through week fifty two while adhering to the protocolized glucocorticoid taper. The question that period two of select GCA answers is, does continuing YUPA compared to withdrawing it after a year result in better efficacy outcomes for maintaining remission while also demonstrating a consistent safety profile. So, let's take a look now at how patients made their way from period one into period two.
Period two of select GCA was a blinded fifty two week extension period coming out of period one. Patients who attained remission in period one for at least twenty four consecutive weeks before that fifty two week visit were re randomized to either get on YUPA fifteen milligrams or switch to placebo in a two to one ratio. In this group, there were sixty eight patients in the YUPA fifteen milligram arm, which we'll call the continued YUPA group, and thirty five patients switched to placebo, which we'll call the withdrawn YUPA group. These two groups were assessed for efficacy comparing continuing YUPA fifteen versus withdrawing YUPA from week fifty two through week one 104. So, Doctor.
Dua, do you mind telling us a bit about the study population and efficacy results in period two of select GCA?
Okay, yes. So, for the patients that were originally in the YUPPA fifteen plus twenty six week taper group and continuing in period two, eighty seven percent of those in the continued YUPPA group and sixty nine percent of those in the withdrawn YUPPA group completed the trial. About three percent of patients in the continued UBA group had prior use of an IL-six inhibitor compared to eleven percent of those in the withdrawn UBA group. The demographics were generally similar across groups. Most of these patients were female.
The mean age was around 70 to 71 years old, and about three fourths of them had new onset disease. And so let's talk a little bit about some of the efficacy endpoints and starting off with one of the most important ones, which is remission. We know that remission is super important since GCA is a relapsing disease, and up to fifty to eighty percent of these patients relapse when glucocorticoids are tapered. So these patients in select GCA entered period two in a state of remission, but the question is how did they do over this next year? When we think about maintenance of remission from week 52 to week one zero four, we can just briefly review the definitions.
Remission was defined as the absence of GCA signs and symptoms and remaining glucocorticoid free from week fifty '2 to 01/2004. So sixty seven percent of patients in the continued UPDA group remained in remission through week one hundred four, compared to only twenty eight percent of patients in the withdrawn UPDA group. And when we shift over to complete remission from week fifty two to 01/2004, that's defined as remission, as we just discussed, with the additional normalization of ESR and CRP from week 52 to 01/2004. In this case, patients in the continued UPDA group were more likely to remain in complete remission through week one zero four compared to those in the withdrawn upa group, with fifty eight percent in the continued upa group maintaining complete remission compared to only fourteen percent of those in the withdrawn upa group. I think this really is pretty impressive and kind of aligns with what we thought would happen, but again, important to have the data to show us that really continuing patients on this maintenance of targeted therapy with upadacitinib really does improve their outcomes regardless of kind of which outcome you're looking at of remission or complete remission in the entire second year of their treatment.
So I think this is gonna be very important because, of course, when you withdraw YUPLA and if you fall out of remission, then, of course, that you're re exposing patients again to high doses of prednisone. So from a quality of life standpoint and from a re exposure to high doses of glucocorticoids, I think this is pretty compelling data that makes us understand the importance of continuing upadacitinib for longer than a year and at least throughout that second year.
Yeah. I agree for sure.
So in terms of outcomes, Select GC also looked at disease flare outcomes in period two. Doctor. Boone, can you tell us a little bit more about the time to disease flare and the relevance of that outcome in your practice?
Absolutely. Time to first disease flare was assessed in period two from week fifty two through week one hundred and four. And disease flare was defined as the recurrence of GCA signs or symptoms, or elevated ESR that required initiation of glucocorticoids. Patients continuing on YUPLA had a ninety percent reduction in risk of disease flare compared with those withdrawing YUPLA, with only fifteen percent in the continued group experiencing at least one flare compared to fifty nine percent in the withdrawn YUPA group. And if you look at the Kaplan Meier curve on the Rx update page for this data, you'll see that flare started occurring relatively soon after stopping YUPA in the withdrawn group.
And I really would encourage you to take a look at this. I think this is probably the striking visual that shows just how different these groups performed. Doctor. Dua, can you talk a little bit about in Select GCA how they fared in terms of cumulative glucocorticoid amounts?
So in period two of Select GCA, patients continuing YUPPA had lower median cumulative glucocorticoid exposure of zero milligrams. Zero. That's amazing. Compared to those withdrawing YUPPA who had a median cumulative glucocorticoid dose of over a thousand milligrams. And I know we've touched on this a little bit so far, but the implications of this lower glucocorticoid exposure is huge.
I mean, especially after that first, you know, year where they are exposed, so many of my patients are just terrified of having to be put back on steroids. So the implications of how little steroids or glucocorticoids were needed in the second year in patients who continued to use back is really important.
Agreed. Yeah. It's one of the most important things we can do is try to get steroids down. I mean, we're seeing this in various clinical trials, various disease states. Some of the trends is how little steroids can we use while achieving the same or better outcomes?
Yeah. Of course. And I think that leads us kinda nicely into safety. Right? Because we we're talking about the safety of these medications.
So in this second year, what is the safety in this population? We know that this is an elderly population, so it's important to discuss benefit risk equation, especially in this patient population. The key outcomes in terms of safety, they retract over about two years for the patients patients who took YUPPA fifteen and for those who received placebo and never took YUPPA. For patients on YUPPA, only side effects that happened while they were on YUPPA or within thirty days after stopping were counted. Overall, the safety profile of YUPPA in GCA was consistent with the profile in period one, and no new clinically significant safety risks were identified with the use of YUPPA for two years.
There were some higher rates of herpes zoster observed in those on YUPPA 15 compared to placebo, and that was 5.9 versus three point zero events per a 100 person years respectively. And, you know, in terms of the herpes zoster data, we know that this is something we are concerned about in elderly population in general, in those on glucocorticoids, and then also in those who are getting JAK inhibitors. So I think this really does sort of highlight the need to discuss vaccinations in our patients. Right? So we have to make sure we have good strategies in place or good alerts when we're in a busy clinical practice to try to make sure we're discussing vaccinations in our patient population.
Do you have any thoughts, Doctor. Buena?
Yeah. I mean, I think this reinforces our need to make sure our patients are getting vaccinated against zoster when they're going on JAK inhibitors. And now, it's not just zoster that we need to think about, but there's other adverse events we need to think about when it comes to JAK inhibitors, and so, let's talk about VTE and MACE. Rates of thromboembolic events were similar in those in the YUPA fifteen group compared to the placebo group with three point three versus three point zero people per one hundred person years experiencing a thromboembolic event, respectively. Looking at the major adverse cardiac events, there were no reports of MACE in the YUPA fifteen group, but there were two in the placebo group, and these both occurred during period one when people were on higher doses of steroids.
So, doctor Dua, how did these patients fare in terms of malignancy or serious infections?
Yeah. Again, really important questions in terms of things that come up in clinic a lot. So the rates of malignancy, excluding nonmelanomatous skin cancer, were similar between YUPPA fifteen and placebo, with one point nine versus one point five people per a 100 person years experiencing a malignancy, respectively. YUPPA fifteen had lower rates of serious infections compared to placebo with five point nine versus ten point five events per a 100 person years, respectively. And so, you know, in terms of how this impacts patients and their tolerability, these are important discussions to have with the patients.
Right? These are the kind of scary new concepts to them. So discussing these are the risks of clots, these are the risks of cancers, these are the risks of prolonged glucocorticoid exposure, these are all really important clinical conversations to have with our patients. But I think this data is really reassuring that in, you know, over a two year period, we really weren't seeing new safety signals in this continued UPPA arm. Doctor Boone, do you have any other thoughts on safety data that's come up here?
I know it's a a huge question that patients are always asking about.
Yeah, I like the way you talked about these sort of trade offs that we face. That's actually one of the things that I often tell my patients, especially when they have a disease that requires more intense therapy. Say there's no solutions, there's only trade offs, and so weighing these trade offs is super important. And it's tough with rare diseases to generate huge numbers of patients over a long period of time, but I think we have a good amount of patients here, and it's reassuring that we aren't seeing any obvious signals from many of these major adverse events compared to placebo with the exception of zoster.
Yeah. And patients are used to hearing the word, you know, steroids or prednisone, and they're not familiar necessarily with a lot of these other sort of targeted therapies. And so being able to really explain that even though you've heard about steroids before, it doesn't mean that it's safe and that there is actually an associated risk of infection is really important to be able to communicate that message and having the data behind it. Having this information is really critical in in terms of educating our patients. So I think those are all super important points.
And just to summarize what we know now from this period two data, the continued use of upadacitinib was associated with maintenance of remission, a lower likelihood of flares, and reduced cumulative glucocorticoid exposure in period two. And as we just talked about, no new safety risks were identified. I think, you know, this is a new mechanism of action that has been approved for this disease, and it's being increasingly used across practices. And I have patients on the treatment, and they ask me how long am I gonna be on it. And now we have good information that lets us know that, you know, if we stop it after that first, you know, year, there's a concern for flare that happens pretty quickly after stopping it.
And so what about you? What do you think?
Yeah. I agree. I mean, kinda similar themes here. We knew from the period one data and the New England Journal publication that YUPLA is an effective steroid sparing therapy for GCA. And while we had some reassuring safety data at the time, the one year time frame had us wondering whether over two years we would start to see some new signals of concern.
Especially, and as you said, this older population that has more comorbidities, and they're at higher risk for complications. So, this two year data really provides some reassurance to me. My biggest takeaway otherwise is just how impressive the sustained benefit of YUPPA was during period two. Eighty five percent of patients having no flares over a whole year is just a really compelling number to me, and probably impacts my desire to use YUPPA and GCA the most. This flare rate was also expressed by the continued use of YUPA reducing the flare rate by ninety percent compared to withdrawing YUPA.
We would probably have been pretty impressed if this number was about fifty percent reduction, but such a big relative reduction by ninety percent really speaks highly of the durability of response to this drug. We're talking about such a high stakes disease like GCA that many people need treatment for for several years. This durability of response is just so important to how I think about treating my patients.
Thank you for joining us to learn more about Select GCA. And listeners, if you would like to learn more about Select GCA period two, take some time to visit roomnow.com and view the therapeutic update on this data. And thank you, doctor Bundo. Was really fun talking with you about this.
Absolutely. Yeah. Glad to be here. This is great.
It is important to note that upadacitinib has a boxed warning for serious infections, mortality, malignancies, major adverse cardiovascular events, and thrombosis. Patients treated with upadacitinib are at an increased risk for developing serious infections that may lead to hospitalization or death. Malignancies have been observed in upadacitinib treated patients. In RA patients treated with another JAK inhibitor, a higher rate of lymphomas and lung cancers was observed when compared with TNF blockers. Non melanoma skin cancers have also been reported.
Periodic skin examinations are recommended in patients at increased risk, and patients should wear protective clothing and use sunscreen. Additionally, a higher rate of all cause mortality, including sudden cardiovascular death, as well as major adverse cardiovascular events, pulmonary embolism, and venous and arterial thrombosis, were observed with another JAK inhibitor compared with TNF blockers in RA patients 50 years of age and older with at least one cardiovascular risk factor. Thromboses have also been observed in upadacitinib treated patients. Avoid upadacitinib in patients at risk of thrombosis. Consider the individual patient's risks and benefits prior to initiating or continuing therapy.
The most common adverse reactions in GCA greater than or equal to five percent are upper respiratory tract infections, headache, fatigue, peripheral edema, cough, anemia, rash, herpes zoster, and nausea. Please also read the additional safety information within AbbVie's November 2025 Rx update on roomnow.com regarding hypersensitivity reactions, other serious adverse reactions, avoiding live vaccines and the importance of immunizations, and medication residue in stool. Review upadacitinib full prescribing information for additional information at www.rxabvi.com/pdf/rinvoke_pi.pdf.
