Activity Transcript

Bruce Kirkham, BA, MD, FRCP, FRACP: Hello, everyone. It's a pleasure to have you join us for this program. I'm Bruce Kirkham. I'm a professor of translational rheumatology at King's College London and a rheumatologist at Guy's Hospital, London, and it's a pleasure for you to join us with the program today called, "Optimizing Outcomes for Spondyloarthritis: Focus on IL-23/-17 Inhibitors."

We've got a great panel today, and it's a real pleasure to introduce Dr Fabian Proft. Fabian's a rheumatologist and senior researcher in the Department of Gastroenterology, Infection and Rheumatology at the famous Charité University Hospital in Berlin. And Fabian's currently a young ASsessment in Ankylosing Spondylitis (ASAS) leader and the inaugural chair of the Young Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Group. So it's great to have him with us.

And also it's a real pleasure to introduce associate professor Alexis Ogdie, who's associate professor of medicine epidemiology at the University of Pennsylvania in Philadelphia in the USA.

So let's get on. We're going to talk about spondyloarthritis, which is a great thing for rheumatologists to look after because it's so complicated. It's a mixture of different things which are all joined together by clinical and genetic and immunological factors. So we have nonradiographic and radiographic axSpA, we've got reactive arthritis, undifferentiated peripheral SpA, which is a real challenge and no one really knows too much about it. We've got psoriatic arthritis and arthritis associated with inflammatory bowel disease.

So these things are all linked and they're linked in many ways. But one of the great things is they're linked because many of the treatments we use actually can be used for the whole group. So Alexis, could you just run through some of the treatments we have available to us at the moment?

Alexis Ogdie, MD, MSCE: Sounds great. So the framework that I'll use is actually one from the American College of Rheumatology and the National Psoriasis Foundation Therapeutic Groups. And so in that situation, the oral therapies are called oral small molecules. These include things like methotrexate, sulfasalazine, cyclosporine, leflunomide, and apremilast. Next, we have the TNF inhibitors, of which there are 5 of them now: etanercept, infliximab, adalimumab, golimumab, and certolizumab.

We have IL-12/23 inhibitor, ustekinumab; and then IL-17 inhibitors, secukinumab and ixekizumab; cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig), abatacept; JAK inhibitors, tofacitinib, and upadacitinib; and finally interleukin-23 inhibitors, guselkumab and risankizumab.

Now those are the psoriatic arthritis ones. If you look at what's available for axSpA, it's specifically the TNF inhibitors, the IL-17 inhibitors, and the JAK inhibitors. The remainder don't have much impact on the axial disease, which we'll talk about more as we get into this, but only those 3 classes if the patient has axSpA.

Dr Kirkham: Thanks, Alexis. So just turning to, why do these drugs work in spondyloarthritis, and why do they work across different things? Well, the things that link it, like I said, are the genetics and the biology that comes from it. And I work with a professor of immunology, Leonie Taams, and we put our ideas together to link the biology with the genetics. And you can see here that you've got this great big cell at the bottom, which is the antigen-presenting cell. And this is all to do about the class 1 genetics, such as human leukocyte antigen B (HLA-B) and that would then interact with CD8 cells. So you probably remember a little bit of immunology. Class 1 genes react with CD8 cells, and it's obvious that maybe these cells are probably important in spondyloarthritis.

Also, the other genetics have quite strong links that lead to the CD8 cells with say the RUNX3 genetics. But also a lot of the genetics relates to pathways, particularly in the IL-23 pathway, where the genes seem to show that cells either make more IL-23 or they're more responsive to it. So you can see that some of the genes also relate to the IL-17 receptors where they seem to give the cells a more reactive response to IL-17. Just fitting in the class 2 genes, there is a sort of idea that maybe HLA-B27 could form this homodimer and interact directly with CD4 cells, but that's still a bit of a theoretical concept.

So if we move into the IL-17, it has this very important role where it interacts in a synergistic way with TNF. And we show that IL-17A and the other one of the family members called IL-17F, both interact synergistically with TNF to really exacerbate or to amplify the immune response. You can see that IL-6 and IL-8, for instance, are strongly related to the synergistic action.

When we look further back, we've also got a synergistic action of IL-17 and TNF in joint damage. But also IL-17 may have a role in SpA, in particular with new bone formation. So that's how you get your syndesmophytes. So this is where the biology actually translates into what we see in the patients.

Now when we're talking about the drugs, again, this is all linked to the biology because monoclonal antibodies either inhibit the cytokines, and we can see here in this very good schematic from Chris Ritchlin, the little blue dots is IL-17A and there's the drugs we all known about with secukinumab and ixekizumab inhibiting that, and there's the new kid on the block, bimekizumab, which actually is a monoclonal which very smartly interacts with IL-17A and -F. These are different types of IL-17. So you get additive activity there, and also you will get synergy with TNF with IL-17A and IL-17F. So the question is, does it give us more efficacy?

We have another drug which inhibits IL-17 pathways called brodalumab. We'll have a little talk about that later. But brodalumab inhibits the receptor, IL-17 receptor A. So as well as inhibiting IL-17A and -F, it'll also inhibit IL-17C and -E. And so brodalumab certainly has quite a wide reaction.

On this slide, you can also see how ustekinumab actually works at the p40, so that'll inhibit IL-12 and -23. Then we have the new p19 inhibitors, risankizumab, tildrakizumab, guselkumab, and these inhibit IL-23 specifically.

And then finally the JAK inhibitors, they inhibit IL-23, but interestingly, they don't actually inhibit TNF directly, and also, they indirectly inhibit IL-17. So we put our heads together with this publication as to how JAK inhibitors are so effective. The JAK1, -2, -3 inhibitors we're used to didn't really directly inhibit IL-17 or TNF, but they're very effective in all these conditions. And we see that there's multiple pathways where they can actually inhibit IL-23, like I said. But also, they can inhibit some of these other cytokines, like IL-9, IL-7, which actually have indirect effects through cells called innate immune cells, which then can reduce IL-17. And also there's the new JAK inhibitor called TYK2, which stands for tyrosine kinase 2.

So we have all these drugs which have really quite effective inhibition on these pathways. And I'm going to pass over to Alexis, who's going to tell us a little bit about some new data on a TYK2 inhibitor. Thanks, Alexis.

Dr Ogdie: The TYK2 inhibitors are now approved for psoriasis. So we're starting to see these in our rheumatology clinic. Deucravacitinib is the first one to market, and in one of the studies presented at the American College Rheumatology Conference, they examined in the phase 2 trial for psoriatic arthritis, whether or not there was an impact on response to therapy, for ACR20 response for example, and the PASI response, the psoriasis response in terms of baseline levels of biomarkers. So they looked at people who had high levels of IL-17, for example, and high CRP, and they found that patients who had higher IL-17 levels at baseline actually did better both from the skin perspective as well as from the joint perspective in terms of response. So it was interesting, mirroring exactly what you just said, that TYK2 does seem to have some impact on IL-17 levels.

Dr Kirkham: That's really interesting. So now we've talked a lot about all these different drugs and we've talked about some of the biology, but how does this all fit together? So the good news is we have these really well thought out guidelines coming from international bodies. Fabian, could you take us through a couple of the latest guidelines coming up?

Fabian Proft, MD: Absolutely, with pleasure because I think this is very unique that in 2022, we had the GRAPPA guidelines for clinical decision-making in PsA patients, but also the ASAS-European Alliance of Associations for Rheumatology (ASAS-EULAR) guidelines for axial SpA patients, where we have some guidelines on how to best select the treatment for our individual patients.

And when we are looking for the GRAPPA guidelines, with which we are quite familiar, that here the domain of the patient that is mostly affected, is driving the treatment decision. And that we can check if our patient that we see in the clinical routine is mainly suffering from peripheral arthritis, and then we have some evidence-based decision-making. Which treatment would be best for this specific patient or is it rather the axial disease that is having the strongest impact on my patient that I'm seeing in clinical routine? And what was new in the GRAPPA guidelines that also the associated comorbidities had a stronger role and that also comorbidities were taken into account.

And when looking at the ASAS-EULAR guidelines or treatment recommendations, they were quite similar in the phase 1, which was very important. I think this is important to highlight here that in the ASAS-EULAR guidelines, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was totally taken out. So only Ankylosing Spondylitis Disease Activity Score (ASDAS) is recommended as a tool assessing disease activity in our axial SpA patients in clinical routine and clinical trials. And I think this is something that we should highlight and give to the audience that, in the future, please use the ASDAS score when assessing disease activity in your axial SpA patients.

And what was also very important, that here again, it was changed a little, the most recent evidence about IL-17A inhibition was also taken into account. So all 3 modes of actions, TNF inhibition, IL-17A inhibition, and JAK inhibition, can be prescribed as first-line treatment options in our clinical routine in our axial SpA patients.

But, it is also mentioned that current practice would be to start with a TNF inhibitor or IL-17A inhibitor. And especially also some circumstances are specified because if we have a patient suffering from recurrent uveitis, we should prioritize a monoclonal anti-TNF antibody in those patients. And it's the same for patients suffering from active inflammatory bowel disease (IBD). So here again, we should choose a monoclonal anti-TNF antibody.

And it is different if we have a patient with axial SpA, but also significant psoriasis which is causing a reduced quality of life for our patients. And here an IL-17A inhibitor should be prioritized in those patients.

And what was also important is that if a patient is failing to respond to 1 or all of those therapies, we should take a moment and reconsider if our primary diagnosis was correct or if we maybe misdiagnosed this patient because fibromyalgia is the main clinical symptom that is in the picture, or we have rather other causes for seeing inflammation in the magnetic resonance imaging (MRI) [scan], mimicking axial SpA, and I think this is also very important for our clinical routine.

And because we are speaking today about the whole concept of spondyloarthritis, and Alexis already mentioned some specifics about PsA and I was speaking about those, I think it is also very important that we go into detail about which are effective in both of those phenotypes and also where are the differences because we know that TNF and IL-17A, they seem to be effective in both specific diseases, in PsA and axial SpA. It is also the same for the JAK inhibitors, but when we are speaking about IL-23, here it seems to differ, because we know that IL-23 is not effective in axial SpA, but it seems to be also effective in the axial manifestation of psoriatic arthritis. And I think this is a very important point for discussion that we'll touch a little later, as well.

Dr Kirkham: Thanks very much, Fabian. Very important. So with all these new drugs coming through, we are getting quite a lot of things. In some ways in the old days you just had TNF. You didn't have to think, you just choose 1. What are some of the reasons why you think we need some of these new drugs?

Dr Proft: I think we can be very happy about the treatment armamentarium that we are currently having, because this really much improved over the last years. And I think that still we are looking enviously to the dermatologists because they have PASI responses of PASI 90 or PASI 100 in a really substantial part of their patients. So they cannot cure it, but they can treat it such that the patient is not affected from the disease at all.

And when we are looking at our axial SpA, and it's quite similar also for PsA patients and we are comparing the treatment response rates from clinical trials, we can say that roughly 50% of the patients are having the treatment response that we are aiming for. But this also means that the other 50% are not reaching the treatment goal that we are setting. And I think this makes it very important that we are still trying to improve our treatment options and that in those patients not responding to therapy, we are trying to find a way to also improve their lives.

Dr Kirkham: Alexis, what have you got for us?

Dr Ogdie: I think that's exactly right. Still, a large number of our patients aren't reaching remission, and so we need different options for them and sometimes you don't hit the right one the first time and so you have to cycle to a new one. So I think having those options is really important. Down the road, we may look at combining some of the biologics. I think that's something that’s coming up in gastroenterology [GI] and starting to come up in PsA. So there's lots to come in how to pick up therapy, but at least for now we do need all these options for the right patient.

Dr Kirkham: Yes, it's interesting because we're looking at a big, big survey of all our drugs and all our patients, and it's interesting that spondyloarthritis in particular is a real challenge, because you're treating 2 or 3 things at once sometimes. So sometimes the joints are great, but their skin's no good, so you'll have to change drugs. And then sometimes, this is where your point is really important, that actually one of these days, we'll be able to use more than 1 drug, which will be pretty nice to do, I think.

So look, Alexis, we’re here to talk about some of the new drugs. There’s an opportunity to share with us a bit of insight into one of the new drugs coming through, the IL-17A and F inhibitor I mentioned, bimekizumab.

Dr Ogdie: Yes, so bimekizumab -- they recently presented their data over the last year and published some of the findings from their phase 3 trials in psoriatic arthritis and axial spondyloarthritis. In the psoriatic arthritis trial, it was called BE-OPTIMAL. This was a 16-week, double-blind, placebo-controlled trial with an extension as well in which they examined the response of bimekizumab compared to placebo in biologic-naive patients with active PsA.

What they found, and you can see the results here, that the ACR50 was actually their primary outcome. So this is one of the first trials to push beyond ACR20 to ACR50. And then they also reported PASI 90, again pushing the bar a little bit further in PsA trials for psoriasis where usually PASI 75 is reported. So what you can see is the ACR50 and PASI responses here. And as expected, bimekizumab was significantly better than placebo.

The nice thing is we have an adalimumab comparator arm here and so this is a side-by-side comparison. No statistical comparisons, but you can see that it's at least as good as adalimumab for the ACR50 for those joint outcomes. And then it does better than adalimumab for the skin outcomes, which we would expect with this IL-17A and -F inhibitor. So nothing terribly new there.

And we also see that it does have a relatively quick onset time, compared to placebo at the very least. And this was also true in biologic-inadequate responders. So among patients who had an inadequate response to at least 1 TNF inhibitor, they also tested bimekizumab vs placebo and actually founded quite strong responses. So the response was similar to that seen in the biologic-naive patients, which is unusual in PsA. Usually we do see a drop-off. So at least that's the first look at bimekizumab. In the US, we're still waiting for this, but I know that you guys have had this for some time available.

Dr Kirkham: Yes, our dermatologists are using it, so that means we get friendly with them and we can share it with our patients sometimes.

So, Alexis also, I mentioned the drug called brodalumab, which has been around for a little while. There were some really successful clinical trials, but it was put on hold because of an adverse event of low mood and depression. But it's coming back with more studies now. So could you take us through some of those studies?

Dr Ogdie: So back several years ago, brodalumab was being developed for psoriasis and concomitantly being developed for PsA and axSpA. So they were running those phase 3 trials having had some relatively strong phase 2 trials. The phase 3 studies for psoriasis closed, while the phase 3 studies were ongoing for axSpA and PsA. And what they found in those psoriasis trials, that there was an increased risk for suicide and suicidal ideation. And because of that they actually stopped the trials for PsA and axSpA. And then it took a long time for them to publish that resulting data. And so this has been recently published now both for both PsA and axSpA, the brodalumab data. And what they found is it looks really identical to any one of our other IL-17 inhibitors and in these smaller populations of PsA and axSpA, there was really not much of a signal for the suicidal ideation as had been seen in this very few number of patients in this very large psoriasis population.

So as far as I know, this is not going to be available to us, at least in the United States, for PsA and axSpA, but at least for our patients with psoriasis who are using this drug, we know now that it works quite well for PsA and axSpA. So the data are at least out there now.

Dr Kirkham: And then one of the things coming through is the head-to-head studies, they're starting to come through. So maybe take us through a couple of the ones we've seen in psoriatic arthritis.

Dr Ogdie: Right, so after the initial guidelines in which IL-17 inhibitors were incorporated, they were incorporated after a TNF inhibitor, because there really hadn't been a head to head to say is 1 better than the other. And so since then we've seen 2 different head-to-head trials of an IL-17 inhibitor vs adalimumab. So we have ixekizumab vs adalimumab, that's the SPIRIT head-to-head trial, and then secukinumab vs adalimumab, and that's the EXCEED trial.

And so what we're seeing first is the SPIRIT head-to-head trial and they had a primary outcome that was different than most of the other primary outcomes. So it was an achievement of a composite of ACR50 and PASI 100 at week 24. So you had to achieve both in order to achieve the outcome. And if you use this outcome, as would be expected, because the psoriasis we know that the IL-17 inhibitors do a better job with the psoriasis than the TNF inhibitors, you'll see that the patients who were on ixekizumab did better than adalimumab with that combined outcome.

When you pull those 2 outcomes apart, you see really what we saw with bimekizumab and what we will see with EXCEED, is that ACR50 responses were quite similar for ixekizumab and adalimumab, but the PASI 100 and PASI 90, for example, were much better for ixekizumab compared to adalimumab. So that really drove that overall composite outcome response.

So when we look at EXCEED, they use ACR20 as their primary outcome and as would be expected, they were quite similar in terms of secukinumab vs adalimumab. They had similar ACR20 responses in this head-to-head trial. Interestingly, the P value was .07. If they would've analyzed it just another way, it would've been statistically significant, but overall I think really still tells the story that IL-17 inhibitors were quite similar for the joints to adalimumab, and they're just much better for the skin. So that helps us also know where and how to use these medicines, as well.

Dr Kirkham: But I think at the time, particularly in the SPIRIT head to head, there was still a lot of discussion about, "Oh, these IL-17 inhibitors, they're great for the skin, but they're no good for the joints," but I think that really put that to bed. Now the same thing is happening in axSpA, Fabian. So could you run through some of the things there?

Dr Proft: Yes, absolutely. And I think here again we can say that we are not only enviously looking at the dermatologists, but also enviously looking at the PsA specialists because they are always a little bit ahead of us as axial SpA experts, because here they already have the head-to-head data, they have data that we were looking for, for years and also treat-to-target data. So we are running a little behind, but I think it's great that we can also speak about these data now today.

And as Alexis just mentioned for bimekizumab and PsA, we also have axSpA data now published and presented over the last year from the BE MOBILE 1 and 2, phase 3 studies. What was quite important was that we have not only focused on the progressed phenotype of radiographic axial SpA but we included patients with nonradiographic in the BE MOBILE 1 and with radiographic axial SpA in the BE MOBILE 2 study.

And we saw quite similar treatment response rates in both subcategories. And recently, we also saw the week 52 data, so also some longer-term data. And we can conclude that bimekizumab is quite effective also on the axial skeleton in axial SpA. And we can also say that it is almost the same effective in nonradiographic as it is in radiographic axial SpA.

And we also have now the long-term data from the phase 2 studies up to 3 years and we can say that it is quite safe in our patient population with the known side effects, which were especially nasopharyngitis, upper respiratory tract infections, and fungal infections that were also known from the PsA and psoriasis (PsO) patients.

And also because Alexis was highlighting also brodalumab and there was the phase 3 study just recently published of brodalumab in axial SpA from Japan, Korea, and Taiwan. And it was exactly like Alexis has mentioned, that here in Europe and also the US, the study program has stopped because of the safety concerns. But when we are looking at the data that was published from Asia, we can say that brodalumab seems to be effective in axial SpA, which is quite relevant for us. And also that there were no suicidal behaviors and also no significant depression differences when compared to placebo.

Dr Kirkham: Thanks Fabian. So these drugs are very close to getting into clinics and probably everywhere, so it's great news, but the other thing is there are more drugs coming in the pipeline. So, Fabian, do you want to just run us through some of these new drugs? We've heard a little bit about the TYK2 inhibitor. What about the other ones there?

Dr Proft: Yes, and I think this was a really fascinating year, 2022, when we were looking for new treatment options in SpA in general, because as we have already discussed on deucravacitinib as a TYK2 inhibitor with promising data in PsA. And then we have also new modes of action and new IL-17 inhibitors with izokibep and sonelokimab. And I think the data that were presented were also very interesting and here again also, because they seem to have a higher penetration of the different specific tissues.

And here, very interesting data on enthesitis were presented for izokibep at the ACR and I think this is still one of the very challenging clinical patients that we are seeing with refractory enthesitis and we cannot really go through it. And to have a mode of action that is specifically targeting enthesitis, would be of very high relevance in our clinical practice in the future.

Dr Kirkham: Thanks, Fabian. And so these are very small particles? They can get into places that the big molecules can't. Is that the theory?

Dr Proft: Yes, exactly.

Dr Kirkham: Fabian, the p19 and IL-23 inhibitors, they've been tested in axSpA, so what's the current view about their role in treatment of axSpA at the moment? 

Dr Proft: Thank you, Bruce. Yes, well, we know that IL-23 inhibitors, we are having them now for PsO patients and for PsA patients with quite satisfying results, and my patients that are treated with it, they really like it. But when we are looking at the clinical trial data in axial SpA, we need to say that was not showing the results that we hoped for, and therefore, I think that most likely, the IL-23 inhibition mode of action in axSpA will not come to our clinical routine in the future.

Dr Kirkham: Yes. Now, you were talking longingly about a head-to-head study in axSpA. So the great news is we've got data you can present to us. So tell us about that.

Dr Proft: Yes, as mentioned before, we are from a time aspect, a little bit behind PsA. So we have at the ACR, this was presented as a late-breaking abstract. The SURPASS study data, which was comparing secukinumab with adalimumab and the main target was the radiographic progression, still a very hot topic in axial SpA. And I think this is important because also the inclusion criterion was that the patient needed to have radiographic axial SpA, but they were preselected, also having high risk for radiographic progression. So having high disease activity and having either high CRP and or syndesmophytes at a study inclusion.

And so secukinumab in both dosages, with 150 mg or 300 mg, were compared with biosimilar adalimumab in a relevant number of patients, and then after 2 years, the primary outcome was the radiographic progression as the modified Stroke Ankylosing Spondylitis Spinal Score (mSASSS) change from baseline, was assessed. And when looking at the radiographic progression, there was almost no difference between the different dosages of secukinumab, but also not when compared to adalimumab.

So I think that we can conclude, regarding radiographic progression in radiographic axial SpA patients or at least in high-risk patients for radiographic progression, both modes of action, IL-17A and TNF, were equally effective for inhibiting or slowing the radiographic spinal progression in those patients.

Dr Kirkham: That's great. Really interesting data. Looking forward to the full publication with all the other secondary outcomes as well, too.

So Alexis, Fabian has briefly mentioned psoriatic axSpA. There are some data here about MAXIMISE, which we're briefly going to talk about, and then we'll probably have a little discussion about this because this is becoming a little bit of a hot topic in the spondyloarthritis field. So walk us through that, and then we'll have a discussion.

Dr Ogdie: Perfect. MAXIMISE was the first trial of psoriatic axial disease or axial PsA. In order to get into this trial, which was secukinumab vs placebo, but these patients had to have psoriatic arthritis but also clinician assessed spondyloarthritis and a BASDAI of greater than 4. On the BASDAI of greater than 4, they had to have a spinal pain of greater than 4.

So really still clinically based. I guess you could say consistent with how we might make clinical decisions in clinical practice. I think some of us rely more on imaging than others. Not everybody had to have MRI evidence, for example, to come in, but they did do an MRI at baseline for at least a subset of the patient population here.

And so what we see is that as you would expect for an ASAS 20 response, patients who received secukinumab did better than patients who received placebo. And as also would be expected, the MRI scores improved more in patients who received secukinumab, compared to placebo, and that was also statistically significant.

So this, like you said, opens the bigger can of worms, which is what is axial PsA? How do we define it, and how do we know when it's getting better? I will turn back to you to start that conversation.

Dr Kirkham: Well I think, Fabian, it would be great to have your view over here, because there's the clinical assessments which you mentioned, the BASDAI is maybe not the one we should be using and is the ASAS outcome measure being tested in psoriatic SpA at all?

Dr Proft: I think you just gave me a perfect pass because I think we still don't know what is axial PsA and everybody defines it in a different way, because for me, to really say this patient is having axial involvement of his or her psoriatic arthritis, I want to see imaging prove that there is something and I would not make it only based on a clinical assessment.

Because we just recently had a screening study where we saw patients with psoriasis having back pain that was chronic and started before the age of 45 years. And then we had in 100 patients, we saw them clinically and had MRI of the whole spine and sacroiliac joints and we saw that neither back pain nor inflammatory back pain was specific for having inflammatory changes in the spine or the sacroiliac joints. And so I think if we would only use the clinical assessment, we would overestimate the number of patients having axial manifestation of psoriatic arthritis.

And on the other side, if we would only take x-rays into account, we would underestimate it because we know that some patients do not show any signs of structural changes in the x-rays, but we see active inflammation in the MRI. So for me, MRI of the spine and the sacroiliac joints needs to be taken into account when making the diagnosis of axial PsA.

And here, there's a collaborative project ongoing from ASAS and GRAPPA, the AXIS study. And this is aiming to define classification criteria for axial PsA. And I think that we all are really much looking forward for those data because I think this will really enlighten us on how to define and how we see axial psoriatic arthritis.

Dr Kirkham: Yes, that's very important. So here, we've also got some studies coming up because the bottom line is secukinumab works in psoriatic SpA. Okay well it works in axSpA, so it's not a big surprise. TNF blockers probably work as well. Well, we do use it in the clinic.

But it's the p19 inhibitors, that's the big thing. They don't really work in axSpA. Do they work psoriatic SpA? So there's a study coming on, so we'll find out about that. I think we could talk about it for a long time, but I think most of us probably would just wait and hope the study is being done properly and we'll see the outcomes. And also we've got a JAK inhibitor study, but I think if we start to wrap up a bit here.

We've talked about a lot of biology, we've talked about a lot of drugs. So what do you think about IL-17 vs TNF blocker drugs in terms of efficacy, safety? Are there any differences? Is any of the new evidence giving us some different way of weighting that combination because the head-to-heads were pretty similar, weren't they, Alexis? Do you think there are any differences coming through maybe?

Dr Ogdie: Yes, that's a great question. In terms of safety, I think that IL-17 and TNF inhibitors, I think they're really on a similar spectrum. I think the 1 difference is that IBD portion or multiple sclerosis (MS), when we have to talk about demyelination with patients on the TNF inhibitors. So those 2 conversations are basically the only differences in my conversation about the therapies.

And then with the IL-23 inhibitors, that's something different, I think, in terms of safety. Those studies have been really long-term data suggesting no real major safety outcomes. I think every one of the listed side effects was equally present in the placebo arm, in terms of prevalence. So it's an interesting difference between the IL-23 inhibitors and the IL-17 and TNFs. Now in a head-to-head study, I wonder if that would look different. So I think that's a question that will come up eventually, too.

Dr Kirkham: That'd be a great anchor drug to add things to, wouldn't it really? Because safety is the problem when you add biologics together. Up to now, the IL-1 and TNF is a real fail; abatacept and TNF is a fail in rheumatoid arthritis (RA). So everyone's a little concerned. Cost obviously could be an issue, but if the biosimilars come in, then obviously that's changed.

So let's move along because we're heading towards the end of our great discussion here. So overall, there's an idea, when you're choosing drugs for patients . . . so Fabian, if you've got a patient in front of you, what are the key things you're thinking about in choosing a specific drug for a patient? Say they haven't had a biologic before already? I'll ask Alexis about the biologic experience.

Dr Proft: I think that when we have a patient that is having axSpA and has no comorbidities and is not having any psoriasis or extramusculoskeletal manifestations, we can choose either of those modes of actions that are available. But when we have extramusculoskeletal manifestations, here are some differences. So I would really, if a patient is having in addition to the axSpA, having significant skin psoriasis, I think that we can clearly say from the PsA study, but also from the PsO studies, that IL-17 is more effective on the skin, and therefore I would choose this mode of action. And when we are having IBD or recurrent uveitis, I think it's quite clear that we are choosing TNF and especially a monoclonal anti-TNF inhibitor. And I think these are the main reasons for me to choose one or the other.

Dr Kirkham: So Alexis, you've got a patient who's failed a TNF. What are the considerations there?

Dr Ogdie: Exactly what Fabian said. So, how severe is the psoriasis, is there IBD, is there uveitis? And then maybe switch. And generally, if they've done very well on that first TNF inhibitor and they were on it for 5 years, let's say, then we might try another TNF inhibitor, because that mechanism clearly worked for them. So I think that's the other aspect is, how long were they on that first TNF? How did they do with that? And then think about switching.

And there are a couple of switching studies now that suggest that this is something, that switching to a new mechanism of action (MOA) is generally going to be better, but they're not statistically significant. We're actually launching the first trial soon to actually test this question. Hopefully in the next quarter here, we'll be enrolling patients in that trial.

Dr Kirkham: Sounds great. And one other thing that's coming through is, the whole axSpA field is becoming more aware of gender issues in terms of diagnosis of axSpA, but also some of the treatment outcomes. Fabian, are there any updates on that you could share with us? Because we're just wrapping up in the last few minutes, but what would you like to share with us on that?

Dr Proft: I think the main important point that I wanted to highlight is what also comes out from the ASAS-EULAR recommendations, that if we have a patient who is not responding to one of our modes of action, I think it's very important to make sure that the initial diagnosis was correct.

And the risk of making a wrong diagnosis is I think, partly higher in female patients because of concomitant fibromyalgia, but also for other reasons that making a positive MRI, because we saw that patients, female patients that just gave birth, they have an MRI bone marrow edema that can mimic axial SpA. And I think it makes very much sense to really confirm the diagnosis.

And there were also very interesting data that were just presented at the ACR [conference] that for a specific mode of action, there can be differences in the treatment response according to the gender. But I think this is something that we need to focus on in the future and better also assess. And I think also in axSpA, trying that in our clinical studies, we have enough representation of female patients.

Dr Kirkham: Brilliant. It's important. So it's all part of the new look. Looking ahead. A lot of things to do. It's been great. We could talk for hours as you could probably imagine. So thank you very much Alexis and Fabian, it's been really great to be able to have a talk with you today and talk about all this really great data. So thank you.

And I'd like to say thank you very much for all the participants. Thanks for being with us. I hope you've enjoyed the session and we're going to log off now, but if you could stay on and answer some questions and also feedback so we can make this even more valuable in the future. So thanks very much for being with us.

This transcript has not been copyedited.