Whats New PsA? (4.3.2026) Save

It's 04/03/2026. This is the RheumNow podcast. Hi, I'm Doctor Jack Cush with RheumNow. This week on the podcast, a lot of reports from the American Academy of Dermatology annual meeting being held this week. A number of reports on psoriatic arthritis and psoriasis, and safety warnings from the FDA on avacopan.

Let's start out with a little bit on pregnancy. There were a few interesting reports on pregnancy this week. One comes from the LUNA registry. This is a registry of lupus patients, followed during pregnancy, and this was a retrospective analysis of first pregnancies, and sought to establish whether there was an association between, fetal loss and, autoantibodies. And, what they found in the study, which was, you know, a sizable study: two forty seven pregnancies, one hundred and ninety four live births, fifty three fetal losses.

They showed that fetal loss was definitely and significantly associated with the antiphospholipid syndrome, or antiphospholipid antibodies. Patients who were positive for those antibodies had a two and a half fold higher risk. Same for patients requiring pulse steroids. Pulse steroids is always associated with bad things because of the reason you're giving the pulse steroids. But there was no significant association with SSA or Rho antibody positivity and fetal loss.

It was an odds ratio of one point three, but it overlapped one, making it not significant. Similarly, other types of analyses showed that when you compared rho positive versus rho negative pregnant outcomes, was no difference in live births, no difference in preterm births. I think the live births were about seventy percent in both groups, and preterm births were about twenty percent in both groups. So again, and I remember this question from my fellowship that was SSA, we know it's associated with, you know, congenital heart block, neonatal lupus syndrome, but, is it associated with fetal loss? And there are some papers that do suggest this.

I do think that this is probably the right answer, that SSA does not increase the risk of fetal loss. An analysis of pregnancy in patients with myositis, either polymyositis, dermatomyositis, five retrospective cohorts showed that myositis patients have significantly higher risk of hypertensive disorder associated with pregnancy, almost a three fold higher risk, and a higher risk, two fold higher risk of c sections. The infants born to women with myositis also had a higher risk of preterm birth, small for gestational age, and intrauterine growth retardation. And those were all significant. You know, there was another study that I think we reported from past meetings, I want to say EULAR last year, and now it came around to publication.

This is a comparison of the pre Cara and the para pregnancy cohorts. And what they did here was they looked at these two cohorts from two different eras. The para registry cohort was two forty five pregnancies, followed from two thousand and two to twenty ten. The pre Cara was two fifteen pregnancies from 2011 to 2023. The pre Cara group were being managed in a treat to target manner, so it was reflecting two different eras of RA pregnancy management, and they looked at time to pregnancy, to conceive and become pregnant in both these cohorts as signs of success.

And it turns out that the median time to pregnancy was two fifty one days in the para group and ninety one days in the pre para group, meaning it was better when women with RA who wanted to be pregnant or were pregnant were being treated in a treat to target manner. Being pregnant within the first year of trying was, also, much higher in the treat to target group, the pre Cara group seventy seven percent versus forty two percent in the para group. And in that pre carer group it was noted that sixty one percent of patients were in remission. So again, smart vigilant management of pregnancy leads to better outcomes. You have to have a healthy mom to make a healthy baby, do you not?

A number of reports on psoriatic arthritis. The Affinity trial was published recently. It was a combination biologics therapy study. It was a pilot study. It was in there a few very large combination biologic studies that are out there.

This one, this was a Jose Scheer's group put this together. It was '91 patients who were active and incomplete responders to prior therapy, and they were given either guselkumab monotherapy or gosselcumab plus galimumab combination therapy. And the primary endpoint in this was going to be the minimal disease activity at, I think it was week 24, MDA. It did not meet its primary endpoint, and that was surprising because most of the new combination trials, especially in psoriasis, look really good, and this is a psoriatic arthritis trial of course, ninety one patients. The MDA was twenty nine percent with combo and twenty two percent with guselkumab, the twenty three inhibitor alone.

Not significant. But all other articular outcomes, including, well, let's put it this way: MDA response was significant when you looked at the patients who had an elevated CRP of greater than 0.3 milligrams per deciliter. And there the odds ratio was like, you know, before it was only one point four, not significant, but if you had the CRP proviso, high CRP, odds of having an MDA response was 12 fold higher. But ACR50, ACR20, ACR70 responses were significantly higher with combination versus monotherapy. ACR50 was thirty two versus five percent, p.

Three. ACR20: 20: sixty six versus forty four percent ACR70: twenty seven versus sixteen percent. So this is highly significant, this is going to go in that list of trials you'll be hearing about where combination therapy, which previously you weren't allowed to combine biologics, right? It's thought to be risky, it was thought to not have additional efficacy and may increase the risk of infections. It is not yet approved, right?

But we're going to see more of these trials coming out, and you know, how you use them has to be, again, with patients with conformed consent. I again, I think this is early data that is encouraging, but not yet paradigm shifting. AXIS was an international prospective study of over four hundred psoriatic arthritis patients looking at rates of axial involvement, depending on how you really defined it. But they found using imaging in twenty seven percent of patients with psoriatic arthritis had axial disease. Patients with axial PSA were significantly younger by only two years, more likely to be male by five percent, more likely to be twenty seven positive twenty two percent versus eleven percent, and have inflammatory back pain not surprisingly seventy five percent versus forty three percent, and they had higher CRP levels.

So this is a different animal, right? And we certainly know that there's some subset we've always said it was I think we always said it was around twenty percent of PSA patients would have axial disease. This one by imaging said it was twenty seven percent. When that's present that might change the paradigm on how you treat them. And we have trials going on in that going forward.

I don't know if you saw this recent data, I want to say this was covered in JAMA, but I read about this on Medscape. Psychiatrists are number one, there's a shortage of psychiatrists. And they use as evidence of that that psychiatrists have a Medicare opt out rate of eight percent. I thought, well gee, that's not that bad. But when you look at all other specialties, all MDs, it's only one point two percent.

If you look at rheumatologists, it's like two to three percent. Medicare opt out rates in psychiatry are eight percent, and that's leading led to a critical shortage of psychiatrists. What are the consequences of that? Well, antipsychotic prescriptions, forty percent of them are being written now by advanced practice providers, nurse practitioners and physician associates. Forty percent.

And why? Well, they're filling the gap that psychiatrists are unable to fill. This is important to medicine overall, health care overall, but it's important to rheumatology. This is going to happen. You can't take care of all RA patients, or all lupus patients, or all spondylitis patients.

And I think APPs are going to be filling that gap, which means that: a) you should be working with APPs b, there should be serious, great educational, onboarding educational programs for APPs when they work with you or in your system, and you should really be demanding that. I know that they're gonna like it. They'll have greater comfort in managing their patients, managing your patients. Another trial, this week looked at RAILD, and you know it's a difficult issue, we don't know what the right therapy is, you know, there are new drugs, there's nintedinib, parfanidone, nirandomolast, but what about DMARDs and biologics? Well, what we've talked about in the past, coverage of ACR and EULAR, is that RA patients who are treated aggressively with DMARDs and biologics have less ILD and less severe ILD, so there is a role.

But which is the best? Or which is the safest? So a target emulation trial was done, and, in this trial they had they found cohorts, six ninety four on abatacep, one hundred and fifty six on a JAK inhibitor, almost 400 on IL-six, seven thirty four on TNF, and after propensity matching, and they compared safety outcomes to patients who were on rituximab. So, are RAILD patients taking those drugs, rituximab, abatacep, JAK inhibitors, IL-six inhibitors and TNF inhibitors, and they found no significant differences when it came to important outcomes like respiratory hospitalization, lung transplant and death. The hazard ratios on these range from 0.74 to 1.09, with no significant difference between them.

The only standout here was that patients treated with abatacept and JAK inhibitors had less death compared to rituximab. Interesting. How much less death? Sixteen percent less with abatacep, thirty eight percent less with JAK inhibitors. Again, is that casual or causal?

Again, this is what you get with target trial emulation trials. They're just taking large cohorts and then subsetting patients and doing comparisons and trying to get a take home message. At best these are not proof of principle, these are hypothesis generating, or they're meant to make you feel good about yourself when no other data is available. Again, at AAD this week, they presented new data on another new TYK2 inhibitor. We have ducravacitinib, recently approved for psoriatic arthritis, approved for psoriasis.

We have behind it another TYK2 inhibitor in play called Zazocitinib, and at this meeting they presented two, large phase three randomized controlled trials called ONWARD I and ONWARD II, and the drug is called envoducitinib. Envoducitinib. Interesting. And it was superior to, in these trials, being compared to placebo and apremelast in seventeen hundred plaque psoriasis patients. So it was superior to apremelast and superior to placebo.

I think that's encouraging data. We'll look forward to more TYK2 development in the world of psoriatic disease. Speaking of psoriatic disease, the big report that we made a big report about about a month ago and when I mentioned the Together PSO trial and the Together PSA trial, the Together PSA trial was presented at AAD and it was also published this week in and rheumatology. So, ixekizumab with tirzepatide is more effective than ixekizumab alone in psoriatic arthritis patients who are either overweight or obese. It's called a Together PSA trial, a phase 3B trial of fifty two weeks.

I think they looked at a thirty six week endpoint, and the primary endpoint in this trial was an ACR 50 plus achieving 10% weight loss. The patients that were enrolled had active disease, they had to have either obesity by BMI 25 to 30 plus a risk factor, or be obese at a BMI of greater than 30 to be enrolled. The primary endpoint, ACR fifty plus weight loss, was achieved in thirty two percent in the combination arm, and only zero point eight percent in the ixekizumab group alone. Many other secondary endpoints also favored the combination. ACR fifty responses alone were higher with the combination, so ixekizumab alone in psoriatic arthritis was twenty percent, ACR 50.

Not bad, but it was thirty three point five percent when you added tirzepatide to ixekizumab, suggesting there may be either the additional clinical benefit because of the weight loss, or there's another additional anti inflammatory or immunologic benefit when you use the combination. Same thing, ACR twenty was significantly higher, as was the MDA response, POSI scores, HAC scores, and FACET scores, the, fatigue, outcome measure. So this is important data, and this will, I think we'll be seeing more of this kind of data in the future, and you know this is another kind of combination therapy, is it not? So The other big report this week in New England Journal was Brepocitinib, a TIC-two JAK1 inhibitor. Two forty one patients in a phase three trial, double blind, randomized, placebo controlled trial in patients with active skin and muscle disease that was felt to be refractory, meaning they did not respond to standard treatments with steroids, DMARDs like methotrexate or IVIG.

So the patients were enrolled, they were treated with the oral drug versus and the oral drug was given as either thirty milligrams of breprositinib once a day oral pill, or brepocitinib fifteen, or placebo. And the Brepo thirty milligrams had a significant response of 46.5, compared to placebo response of 31.2. The low dose brepocitinib was basically equivalent to placebo, so the higher dose was needed. This was very encouraging, great data, but there was one small, Achilles heel to that, and that's serious there was more serious infectious events on the Brepo thirty milligram dose group, a ten percent SIE rate. That's high!

Versus the one percent SIE rate with placebo. That's about what you like to see. We need to see more trials like this, but this seems to be pivotal data that will be used probably in an application for use, right? Last report is the FDA came out this week with a safety warning letter about avacopan and serious liver injury. We had talked about this in the past.

It's in the package insert, it's not really a big surprise, but when they looked at an analysis going up to late October twenty twenty four, just reporting it now, I'm not sure why there's a delay here other than well, it's just it's an FDA safety bulletin. But as of October 2024, the FDA identified seventy six cases of drug induced serious drug drug induced liver injury with that with evidence of reason the wording they used was reasonable evidence of a causal association with avacopan use. Seventy four of the seventy six cases had a serious outcome, including fifty four with hospitalization and eight deaths. Amongst the seventy six were seven cases of biopsy confirmed vanishing bile duct syndrome, VBDS. Never heard of it before this report.

It's a rare disease, a rare complication, and when you look at VBDS on PubMed it's associated with malignancies, and it's been associated with checkpoint inhibitor therapy. It's not been associated with vasculitis, the indication for which you would use avacopan, right? Avacopan approved in twenty twenty one-twenty twenty two, I think, for ANCA associated vasculitis VBDS is not associated or a consequence of that or the other therapies that are used to treat that. So that's sort of bad news, and something, you know, it's still a rare event. There were seven of these cases of VBDS amongst two forty one, sorry, no, among seventy six reports FDA identified.

So one tenth of all drug induced liver injury could have this problem. Three of those seven VBDSs did have a fatal outcome, and that's a little scary, is it not? Anyway, interesting news this week on the podcast. You can go to the website, check out these citations and more. We'll talk to you next week.

Take care of yourself.