APLAR Congress 2025 Save

From Griffith University of beautiful Downtown Brisbane reporting for RheumNow at Bluffley Coker twenty twenty five. There was a very interesting session on hot topics in XBA presented by me, We went through 12 hot topics. One was about early diagnosis. Everybody talks about a window of opportunity as defined by Nigel LaRune's study where erosive disease and drug free remission were greatly impaired if there'd been a long delay in treatment and function disability also twice as bad. And it highlighted a number of studies, including a study that from The US claims data, looking at 97,000 patients, one in three experienced time to diagnosis of over six years and then often seen at least five different healthcare professions annually with an average of 21 back pain related visits before the penny dropped and the diagnosis was made.

In PSA in Britain, a nice study from an English and Welsh audit data set at least four months before the diagnosis between symptoms and diagnosis in that particular data set. Secondly with gender, had been established clearly that females have a higher baseline disease activity, They have a lesser response to therapy, and it's important in trials going forward to stratify for gender at baseline. Females both showed worse or higher levels of BASDI, ASQOL, ASASI, MACI's at baseline compared to males, and they did worse in response to therapy. But it wasn't just sex hormones. GRAP is doing a big study on trying to understand this gender difference.

There was a nice study from group presented at Washington DC at ACR led by Krug et al, which showed some transcriptomic sex specific differences in response to biologics in PSA. So the story looks a little more complicated than just a pain differentiator or a sex hormone differentiator. We moved on to the importance of obesity and how there's a large epidemic of obesity across the Asia region. Upwards of thirty odd, thirty five percent of patients now meet the definition of obesity with a BMI over thirty, and the trend is even on the rise in Japan. We show the similar rising trend in both obesity rates and type two diabetes up to about one in three in The Middle East as well.

We showed that the health impact of being obese, adversely affected, AXPA with high disease activity, greater spinal stiffness, poorer mental health, and we showed also as a risk factor for the development of psoriatic arthritis. And it was the first large scale epidemiological evidence that put those increased risk together. More importantly, a nice study from British Columbia presented at a previous EULA looked at eleven thousand patients with immune mediated inflammatory diseases who happened to have type two diabetes and they compared the patients who were on the GLP-one receptor agonists, about three and a half thousand of them, and this potential weight loss and reduced risk of other illnesses, and they compared them with the DPP-four inhibitors, which don't have the weight loss propensity of the GLP-1s, and they're quite easily able to show that the incident rate of death, stroke and heart attack were significantly reduced if GLP-one was used to treat these autoimmune patients who had diabetes. So we've been encouraging all our patients with a BMI over thirty to seriously consider using these agents for a number of months, lose a certain period of weight, stop the medication if they don't have diabetes, and see if they can fight to keep the weight off.

And the benefit is seen in many areas from lupus flares, gap flares, knee osteoarthritis, rehab and pain across the board now. The number of studies are underway in psoriatic arthritis itself. Recent England Journal paper showed four glycerin, an oral small molecule GLP-one receptor agonist, effective in type two diabetes at controlling sugar, but also significantly and also normalising lipids, improving HDL, reducing LDL and improving the ratio. Further, weight loss has been shown to increase the chances of achieving MDA by a factor of six times. We talked about stopping the patient smoking, the metabolic syndrome, and a cardiovascular risk factor calculation for patients with psoriatic disease as developed by Lihi Eder that showed the disease specific factors that are associated with prediction of risk and the traditional cardiovascular risk factors, and the importance of being a clinician and working on smoking, controlling weight, blood pressure, lipids, fatty liver drugs, depression, and alcohol excess.

One of the hot topics is the prevention of progression of PSO to PSA. We talked about the screening tools for, dermatologists. The PRESTO tool, also developed by Lihi either for psoriatic psoriatic arthritis for patients with, psoriasis. We talked about the PAMPUS study and the ultrasound abnormalities in patients with psoriasis at high risk of progression. We talked about how difficult it would be in a prospective study going forward because each year a patient loses psoriasis, there's about a three percent risk of developing psoriatic arthritis.

So you need big numbers over a long period of time to make a very significant difference. We talked about the increasing recognition of the role of joint fibroblasts in joint damage and about some PET imaging that can differentiate patients who progress and who won't progress, PET showing differentiated by the PET uptake at the synovial entheses using GA FAPI O4 PET uptake at baseline to decide and differentiate. We talked about biologics that may reduce the risk of progression. The phototherapy versus biologic study where the incidence rate was halved in those per thousand patient years, was halved in those patients who received last study where different biologics compared to TNFs showed some advantage in the 23, twelve, twenty three and seventeen inhibition compared to TNF in preventing progression of psoriatic arthritis to psoriatic arthritis. We talked a little about, blood biomarkers in early axSpA and about a panel of biomarkers being investigated in PSA.

Talked about AI where there's some artificial neural networks to improve the detection of definite radiographic sacroiliitis with high specificity. We talked about similar measures in psoriatic arthritis to improve detection of disease. We talked about the development of deep learning algorithms to detect sacroilias on MRI in those patients. And we talked about the vector machine picking up and differentiating nevi from melanoma and the use of those imaging and the superiority of the machine in diagnosing melanoma that needs a biopsy and sent to the dermatologist. We talked about AI, Perplexity, a mobile app that includes multiple GPTs.

We talked about Google GPT, which is a more specific medical GPT, and we talked about hiding a scribing program, which will take notes of your consultation lab to be put into the file, clever enough to remove the niceties and the salutations, and stick to the medical details and a time saving and accuracy measure moving forward. We mentioned the multiple therapeutic recommendations and congratulated the APLAR PSA guidelines, and we talked about combination, sequential, and tapering therapy. Then we moved on to the increasing interest in defining those patients who are treatment refractory or difficult to treat, and the definition requiring objective evidence of inflammation either on sign of either some imaging or inflammatory markers to have failed a couple of biologics of two different mechanisms of action, and contrasted that with complex to manage, where there was no objective of evidence of inflammation, but ongoing symptoms that having failed a couple of methods of action of biologics and those ongoing symptoms due to problems like osteoarthritis, depression, central sensitization, chronic widespread pain, and the management just as valid but not with expensive biologics rather with pregabalin, amitriptyline, physical therapy, surgery, injections, etcetera. We talked about, combination therapy, PNF plus seventeen, TNF plus 23, Jack plus 17, Jack plus 23, with no additional safety signal.

But the rationale was that if you can identify a difficult to treat group early enough, perhaps needs testing of course, combination at baseline and then reduced to maintenance over time, that the evidence you should taper but not stop as all patients flare if you stop. We talked a little bit about being careful with imaging Physical therapy sorry, from physical exercise, from pregnancy can lead to a label that leads to cycling through expensive biologics without benefit, and that one of the rules of the new ASAS guidelines, if the patient does not respond as you would expect, reassess the diagnosis. We talked about the microbiome and the future role of that in management of axSpA and PSA. We talked about the fecal transplant study, unfortunately, did not meet its endpoints, but a nice study looking at the gut joint inflammatory T cell trafficking in a model of SPA and AXPA. And then we talked about, finally, novel targets, including a 17 ANF nanobody, which is said to have better tissue penetration by binding to albumin.

We talked about a new TYK2 inhibitor called Zazocitinib, 1,000,000 times more specific for TYK2 than JAK123. We talked about an antibody called ORCA, which is a 17A modified and allowed an extended half life so it only had to be given every six months or so. We talked about an oral IL-twenty three antagonist, if you like an oral version of guselkumab, and the benefits of this oral agent, poorly absorbed, poorly bioavailable, but so potent that it's still effective in psoriasis, and the PSA studies are underway. We talked about checkpoint inhibition that can induce PSA and that TNF, methotrexate, IL-six, and guselkumab and the JAKs have been shown to be effective in that situation. And we talked about the Asia Pacific region with billions of patients and the advantages now of generic JAKs to allow excellent treatment in poor countries which can't afford access to these advanced therapies.

So I hope you enjoyed that and over to looking forward to catching up at another time. Thank you very much. Peter Nash reporting for RheumNow, APLAR twenty twenty five Fukuoka. One of the very interesting presentations by Doctor Mia Gawat and his group was talking about precision medicine in PSA in particular. He talked about a wide clinical spectrum of disease, he talked about the impact of treatment and he talked about the study they had previously presented where they were able to use flow cytometry to define a number of different phenotypes and then assist in picking which biologic agent would be most suitable for which patient.

He defined a TNF phenotype, he defined a phenotype that responds best to sorry he defined an anti Th17 phenotype, an anti TNF phenotype, a combined phenotype that would be TNF and 17 inhibition, and an activated T1 phenotype that was more along the twelvetwenty lines. When they tried doing that in patients, they had superiority with the strategic group for DAPSA low disease activity or minimal disease activity, but there was no significant improvement in those patients who had the biologic suited to their phenotype compared to those patients who just had a random biologic for dapsa remission. So they went back and said well that's not good enough, it's going to be too complicated to apply in real world clinical situation, there's limited advantage of the strategic treatment, LDA and PASTAS wasn't particularly effective nor was it for DAPSA remission. So they went back and tried to study how they can fine tune this by doing a second study of a new treatment strategy. And the treatment strategy hinged on an identification at baseline which serum cytokines could predict treatment response using a univariate analysis and they looked at a number of options who had these patients with dapsular emission and they found how long do we hold IL-twenty three compared to interferon gamma IL-six TNF IL-17A IL-twenty three was significantly low when the others were unaffected and they set out to study this baseline serum IL-twenty two concentrations significantly lower in the dapsa remission group compared to the non remission group in that group of patients who were treated with IL-seventeen.

So they then set about dividing a group of patients into IL-twenty two low and IL-twenty two high and they looked at both TNF inhibition and IL-seventeen inhibition and the sensitivity of this IL-twenty two cut off was about 82%, the specificity 92% and the area under the curve using a rock analysis was 0.848, they're quite significant. So when they did that, when they compared the cytokine concentrations and the high and the low, they came up with a new treatment strategy based on the IL-twenty two concentration. The IL-twenty two high group were more of a TNA would receive TNF alpha inhibition. The IL-twenty two low group were more of an IL-17A dependent phenotype and they would receive IL-seventeen inhibition and then they did a retrospective validation of that effectiveness of the new treatment strategy comparing strategic treatment TNF1722 high, 22 low against a mismatched treatment group. They followed them for a year and they compared the outcomes over that twelve months and at the end of this study the bottom line was that if you were matched using your IL-twenty two process, as we just defined, the proportion of patients in remission was sixty nine percent.

If it was a mismatch, it was twenty five percent. So almost double better using the IL22 baseline cut off. And if they looked at minimal disease activity, the matched group, even though the numbers were not huge, had reached MDA compared to forty odd percent in the mismatched group. Interesting, something that hadn't been seen before, allowed to some improvement in treatment outcomes when you try and stratify your patient using a precision medicine approach. And I've not heard about this IL-twenty three baseline as a predictor in the past, and clearly bigger numbers, international studies take this a little bit further, but quite a very interesting approach and we're looking forward to the future with this kind of study.

Thanks very much for your attention. Professor Beda Nash reporting here for APLA Fukuoka twenty twenty five for RheumNow. And our first interviewee is Professor Arthur Cavanagh, current president of GRAPA, and he did a lovely presentation about an update in the management of psoriatic arthritis and its therapies. Over to you, Adi.

I said the easiest and the toughest topic, which was treatment selection. Easy because we have so many treatments available to us, but we still don't know which one is right for which person.

So tell us about combination therapy.

So many, many, options, but we're still not doing that much better. We do well with a lot of individual agents. And unlike our colleagues in dermatology who have really blown past what they were able to achieve with CNF inhibitors, we haven't. So combination therapy, which I think has been brought to us back now by the gastroenterologists looking at IL 20 three inhibition and TNF inhibition in combination, show that that can be not only, that it can be safe, which is crucially important, but it was more effective. They had more high level responses.

So I think the question is for psoriatic arthritis, what combinations are we gonna see? When are we gonna see them? And what kind of patient? And some of the audience questions were really great in that regard. Said if you have somebody and their skin is doing great, but they have a lot of enthesitis, what do you pick?

And we talked the whole gamut of adjunctive therapies, conventional synthetic agents,

different mechanisms. Using methotrexate as the first drug?

I think we may well be. I would like to say, you know, it's a drug of the past, but you look at the data, and I showed the data from SEEM PSA and methotrexate. Although we can't really say the there's no placebo group,

so I

can't determine effect size, methotrexate was not that less effective seemingly than the TNF inhibitor or tantorcept or the combination of the two. So I may object to it, patients don't like it, but I think it's not going to go away completely.

And there was a very good question about head to head studies and about the use of placebo rather than active controls. What do

you think?

Head to head studies are absolutely great because it really gives us a chance to say, we can't compare studies done in different periods of time, different countries. This gives us a chance to compare them. But, really you without a placebo, it's hard to get the effect size because that really locks it. We've had problems with placebo responses. When they're high, it's hard to know what to do with the efficacy of a medication.

So I think they're here. I think they're for a short period of time, but I would love to see more head to head studies. Awesome.

Thank you for that, and we really enjoyed your talk. Thanks, Adi.

This is Peter Nash from Griffith University reporting for RheumNow at Fukuoka APLA twenty twenty five. CAR T flavor of the month, Georg Shet gave a couple of presentations. In one of them, he discussed again c d 19 CAR T blocks B cell evolution all the way to the plasma blast, which makes many of the autoantibodies that drive disease, such as SSA, double stranded DNA, j o one, etcetera, and leaves the plasma cell alone to reduce the risk of various immune deficiencies as we'll discuss. But BCMA CAR T, very commonly used in oncology, includes the long living plasma cells and has some detrimental effects downstream. To con confirm this, he showed the vaccinated related antibodies that were not suppressed because these come from plasma cells and CD nineteen CAR T did not interfere with measles, mumps, rubella, zoster, EBV, tetanus, also SARS CoV two vaccination antibody status and protection, a plus for CD nineteen CAR T inhibition.

He talked a little bit about a very interesting case of his with lupus who initially responded to c d nineteen CAR T therapy only to flare some months down the line. A repeat CAR T c d nineteen infusion did not result in long lasting remission. They tried one of the long acting autoantibodies to CD19. This also didn't help. But then they changed BCMA CAR T therapy and have had long term remission over a year subsequently.

Of events for those patients who have failed CD19 CAR T, there is another option. He also went on to talk about some allergenic options, which will mean off the shelf and will mean less cost and easier to access this otherwise expensive therapy. He talked about the advantages of CAR T, which include that the infection risk is low, the organ toxicity is low, cancer risk is low, and family planning is possible. He talked about one patient who delivered a normal baby, another patient who in her fourth year of drug free remission is pregnant at the present time. He also talked about the cons.

It's expensive. It's a complex procedure. The necessity for lymphodepletion, particularly using a genotoxic vidarabine, and the effect of repeated exposure is unknown. We talked about potential solutions for these methods, including allergenic c d nineteen CAR T, which they tried in one patient with severe myositis with good results. And they talked about a very interesting new method where they're making a nanobody a nanoparticle, sorry, with mRNA in the middle.

This is an animal, experiment. So they used this lipid nanoparticle with an mRNA payload to make the CAR T and to induce the remission. Problem, as always, is these are individual case series, individual cases. It's about time we had some controlled trials because we're not learning anything. We're not learning if lymphodepletion is a must.

We're not learning if lymphodepletion is exactly what causes the improvement rather than the CAR T. We're not learning about a control against, for example, CD 19 monoclonal antibody or against a T cell engager. We're just seeing individual case series who are doing well. Some of them up to four and a half years of drug free remission when they had very severe disease. And so we need to move this process further to define what's the absolute requirements and what we could get away without doing in some of these otherwise very young, patients with a lot I watch this space of an exciting intervention that may rewrite the way we treat some of these very, very difficult diseases in the appropriate patient.

Thanks very much. Professor Peter Nassi reporting for RheumNow in Fukuoka, APLA 2025, and we interviewed Lai Shantan, who did two fantastic presentations. The first one that we'll be discussing with her is the use of micro CT low radiation in imaging psoriatic arthritis.

Can you tell us a little bit about the QCT technique and whether you think it should replace x-ray, which is so insensitive in psoriatic arthritis?

So thank you, Peter. This is a wonderful question. So we've been using this HRP QCT for the past ten years. By just imaging three joints in the MCP, we can monitor the progress of firm damage in terms of erosion, as well as new bone formations. So we have just published our data using IL-seventeen compared to placebo, and we can see there is a significantly higher efficacy for IL-seventeen to prevent erosion progression as well as the enthesiophyte progression as well.

And the enthesiophytes is like pathognomonic of psoriatic arthritis. Yes. And you can see it so beautifully with your three d images that

you showed. Exactly. So this cannot be shown on x-ray. So basically, I think in the future, we definitely can replace CT using this new machine.

And the radiation is quite low?

Very low and very high resolution, yeah.

And can you see healing? Can you see change in a positive way?

So this is actually the most interesting question. So previously using x-ray, we can't actually, well damage is damage, okay? But now using this sensitive imaging technique and powerful medication, we are actually seeing a partial erosion healing in patients treated with ileocephinin inhibitors or patients who can achieve sustained remission or low disease activity.

So one of the things

we commonly get referred from the dermatologists are patients with primary nodal osteoarthritis long standing, they have psoriasis and painful fingers and they say, is this PSA? Is it not? Could your technique help us in that differential?

That's also a very good question. So using this new technique, we can actually differentiate new bone that are developing in the joint margin, in the cartilage margin. These are osteophytes, typically found in patients with OA. But for patients with psoriatic arthritis, we are seeing the new bone developing in the emphases. So this is a pathognomonic of PSA.

So the answer is yes.

That would be hugely helpful. So thank you very much, and congratulations again on the presidency of APLAR.

Thank you very much.