Focus on Guidelines Save

I'm Jack Cush with RheumNow. As you know, in this month, we are featuring TNRs that are addressing issues of importance to advanced practice providers. It's part of our campaign this month called APP Partners in Care. Last week, we had a great discussion on hiring, onboarding and training. Tonight, we're going to discuss more importantly, room cases and how nurse practitioners and physician assistants, advanced practice providers manage cases that we all see, and how you interact with either your rheumatologist or your APP colleagues.

I'll have our great panel introduce themselves. I'm Jack Cush in Dallas, Texas. Audrey?

Hi, thank you for having me. I'm Audrey Gibson. I'm a physician assistant in Gainesville, Georgia.

Ben.

Hi, good evening everyone. I'm Ben Smith, a physician assistant rheumatology in Thomasville, Georgia.

Emma. Hi

everyone, I'm Emma Babbage. I'm a Rheumatology nurse practitioner from Tasmania, Australia.

Yes, just right around the corner from Georgia. So let me start with our slides and our cases. I want to thank our sponsor for this campaign month. There's five great sponsors AbbVie, J and J, Lilly, Novartis and Sanofi. It's really great that they stepped up and underscore the importance of APPs in rheumatology practice.

So this is our panel for tonight. I wanna remind all of you that again, this month we're doing Tuesday night rheumatology on these important topics. Tonight, room cases and the importance of guidelines and co management. Week, APP controversies and misconceptions, that's gonna be a great session. And our final week, right before Christmas, comorbidity and health management.

So, I wanna begin with our first case. This comes from, Audrey Gibson. Audrey, do you wanna present this or do you want me to present it?

I can present it. We can start there. All right. Let's see if I can move this out of my way though, so I can see the whole slides. Okay.

So this is kind of a classic presentation, I think of a patient with psoriatic arthritis and I'll kind of take you through his journey and what treatment decisions were made and how we got to kind of hopefully a level where he was at low disease activity, hopefully remission. So this is a 34 year old male. He was referred to our office actually by a dermatologist, but he was referred to our office for new onset joint pain, swelling, increased morning stiffness lasting greater than an hour. He described episodes of bilateral wrist swelling, as well as he also had swelling in the right third toe. So, when we started talking about his history, he had had a history of psoriasis for the past four years and had failed topical corticosteroids and UV light.

He had also had a trial and fail of a Primilast. He had also been on ixekizumab for about a year which initially he did very well with but then he started having some breakthrough psoriasis. So at that point the dermatologist initiated Rizikizumab where he had a really great psoriasis response with about 90% resolution. Unfortunately after being on Rizikizumab for about a year, this is when his joint symptoms started. And that's what prompted the referral to our office.

So, on physical exam, he had evidence of synovitis at the wrist, the PIPs. He'd had a normal Sjogren's test and he did have evidence of dactylitis at the right third toe. So, past medical history includes history of psoriasis. Otherwise, no other relevant past medical history. And based on his exam and findings, we diagnosed psoriatic arthritis with the evidence of psoriasis there.

So, you know, at that first visit really talking with the patient, his psoriasis was doing quite well on his current regimen. So really it was that joint inflammation that started to become a problem and what we decided initially was to add methotrexate to his current regimen and use this in combination. Unfortunately, at his follow-up visit about six weeks later, his labs indicated that he had elevated LFTs and we had to discontinue his methotrexate therapy. So again, we really had to consider which pathway we were gonna go for this patient. He still had active joint inflammation, but the skin was relatively well controlled.

And what we decided at that time was to switch his IL-twenty three to TNF adalimumab, forty milligrams every other week. We got him back for his follow-up visit and unfortunately he still had persistent risk synovitis and unfortunately he had worsening of his psoriasis as well. So again, we kind of had to take a step back, have a discussion with the patient you know which were the aspects that were really predominant really active and interfering with his day to day activities and then what treatment options did we have for this particular patient who had a history of you know peripheral arthritis, psoriasis, as well as dactylitis. At that point, we made the decision to switch him to a JAK inhibitor. Thankfully, with his follow-up, he was doing much better.

His psoriasis had about 90% improvement. His synovitis had resolved, his stactylitis had resolved. And so now we're just monitoring him closely, monitoring his labs and for any kind of recurrent of skin and joint inflammation.

So this is a great case. It's got so many left turns, right? And it really challenges you. I'm going to ask a few questions that I want to know where you guys sit as far as practice. Methotrexate and psoriatic arthritis, do you use it?

Is it the evil you have to go through to get to the therapies you want? Audrey, what do you do?

So I definitely have found that over the past few years, I'm using less methotrexate in my psoriatic arthritis patients, mostly because, you know, we know that it has limited response, especially in certain domains. We also know that these patients have a high level of comorbidities. And so you really run the risk of metabolic syndrome, liver toxicity, risk of infection. And then of course, even with this patient, he's 35 year old male, he's still in this child bearing age. So, that is also a component that you have to consider.

I still use it sometimes in combination with patients that have more peripheral arthritis that maybe are just not goal or not to that remission state. And then I still find some pushback from insurance companies that we have to kind of jump through that hoop in order to get other therapies approved.

Right, so it's in the insurance and that the whole thing that often drives it. Ben, do you do this differently? Do you always just go through methotrexate and try to move on as soon as you can?

No, not necessarily. Certainly maybe in milder psoriasis cases we might consider methotrexate, but I think the 2018 ACR guidelines together with NPF guidelines, if you wanna say gave permission to think about biologics first and others, I think we have that opportunity, of course, often limited by insurance. But I think working with other specialists in this realm often helps with that because patients come having tried other things prior to seeing the rheumatology team.

Yeah. The derms are great to work with because they have the clear hierarchy of drug response where we don't. All of our drugs seem to do the same in psoriatic arthritis, but their drugs clearly are very differential responses with IL-twenty three inhibitors on top challenging now by the dual IL-17AF inhibitors that are being developed, the one that's currently on the market. Then IL-17s and then TNFs, then JAKs, as far as skin responses. Emma, you have the same availability of drugs, do you not?

We do, but we are restricted by our funding source. Here in Australia, we use methotrexate first line for everyone who comes through with psoriatic arthritis, unless there is a contraindication. Our guidelines say we have to trial two DMARDs for at least a three month period before we get access to any of the biological agents or a JAK inhibitor. So certainly we use it and we do see some good responses and we see some good responses with both skin and joints. I think it's still a worthwhile medication to use.

I certainly still in a 35 year old male, I would use it. I would start off at a lower dose and work up to twenty. That would be my-

The reproductive guidelines do say, although I have a recent report on RheumNow that argues against this, and it comes from one of the Southeast Asia registries like Korea, that male exposure to methotrexate in all DMARDs really is not a risk factor to the fetus. It's always been a worry and a concern, but male exposure generally shouldn't be and there are guidelines that support that. But a recent report out of Korea said, Oh, no, not so fast. I don't know what that means when the preponderance of observational evidence says otherwise.

I think that's when it comes back to you need to have a really good history on these patients. Where are they in their fertility? What are they doing with their family life? We know we can wash out methotrexate as well.

Right, exactly. I think we're allowed to use methotrexate really because of the PSA seen data, which really defined the efficacy of it in at least half the patients. It's a good idea. But when it comes to moving on like this case, the patient had been on a Primalas, IL-seventeen, IL-twenty three, and then methotrexate. What did you use, Audrey, in choosing your next?

Do you think about the domains and GRAPA guidelines or do you just have your hierarchy of what you're going to use next?

No, I definitely refer to the GRAHPA guidelines and definitely I look at that domain based approach when taking care of patients with psoriatic disease. And I think the domain based approach, it really does help give you a clinical framework to really help structure real world decision making. So, you look at the GRABA guidelines, they don't give recommendations about which drug to use first. They just say these are the drugs that you can use in these specific domains. So then it comes down to really that shared decision making with the patient.

They prefer a pill? Do they an injection? Does their lifestyle accommodate or does it fit better with maybe an infusion? So you kind of use that information and really what the goals of the patient are to make the best decision that you can about how to proceed forward if a drug is not working or a patient is failing therapy.

Yeah. So Ben, I think you pointed this out that they're all equal and they're all equal because one, there's no head to head trial that says one's better than the other and two, they all played by the rules that say you can use it whenever you wanna use it. How else have you used these guidelines?

Yeah, thank you for that point. I think the image that you're projecting now is artwork in medicine because I returned to this image often and the previous version of the guideline as well, because I think this is very, very helpful. And I really commend Audrey's approach on the case, how she really went step by step mechanism of action by mechanism of action to try to find what was the right fit for individual patient. In the future with precision medicine, perhaps this image is gonna look much different possibly. But I think thinking in these domains, there's an application not only for psoriatic arthritis, but also other rheumatic diseases as well, as we think about how persons present with manifestations.

But my approach is very similar to describe, I highly use this GRAPA image as a reference, as we think about how to approach it for the patient.

I love it too. I think it's the best of all the guidelines out there because it's so clear. May not say that you should use an IL-seventeen AF inhibitor ahead of an IL-twenty three, but at least it lays out maybe what you shouldn't be doing. Emma, when it comes to making this next choice or your third choice or your fourth choice, what's gonna guide you? Is it going to be patient request, your preference and experience, or the patient's underlying comorbidities that really limit you one way or the other.

And I think it's all three of those things. I think the first thing I'd ask the patient, as what Audrey did, is what's bothering you the most? Because sometimes they'll come to you and you'll think that their dactylitis is going to be their issue, but actually it's the psoriasis they've got on their upper arm and they can't wear their strapless dress that they want. So I really feel like when we're making these decisions, has to be involving the patient at every choice. I would also in someone like this, I'm really lucky I work in a really fabulous multidisciplinary team.

I would get them into the physio as well, get them moving. This is a psoriatic arthritis patient. We know they're going to have metabolic dysfunction. They're most likely going to be overweight. Let's get them moving as well.

Yeah. I want to first remind the audience if you have any questions, put them in the Q and A box and that way we'll be able to address your questions on these cases. And I think we certainly would love to engage you on anything that you think is important. I wanna go back and look at this case and let see if I can get this back. So we're at the point of good control of synovitis with upadacitinib and risankizumab, the the IL-twenty three inhibitor?

No, just upa.

Okay. So I guess that's the question. Synovitis has done great, dactylitis has done great, but you're not quite at 100%. How hard do you fight and would you go further, Audrey?

So again, I think it really is patient driven. I think probably the location of that residual psoriasis, can you manage that with topical corticosteroids? Can you manage that with some, know, other non pharmacological agents or is it in an area that the patient is not really bothered by it? Because I think just like Emma had mentioned earlier, you know, I have some patients that they, you know, they get that joint inflammation under control. Maybe they have a little bit of psoriasis, but maybe it's behind the ear, you know, maybe it's not in a very prominent area and they say, Hey, I can live with this.

You know, and if that's the case, then I think that, you know, I would be okay monitoring and managing the patient as they are. Now, if you have a patient that says, No, you know, this is in a prominent area, maybe it's, you know, face or scalp that's pretty, you know, debilitating for a patient, you may work to, you know, be a little bit more aggressive with how you treat it.

Do any of you have a combined rheumatology dermatology clinic? I wish I did.

I did too. Yeah,

like on this case, you have your ideas, but this is where in my community, have incredible world class, famous medical dermatologists who do all the psoriasis trials and drug development. And I just text them, well, okay, on our patient, you know, X, Y, Z, how do you manage? That seems to work out well. Any last comments on this case? Any other options?

Would anybody do combination biologic targeted synthetic therapy?

I will say I have in certain cases with really refractory joint inflammation and skin involvement. I have used combination therapy in those patients when necessary. Now that's a handful of cases, not very many. And then of course there's always the issue with payer coverage in those patients, but I have done that with quite good success.

Yeah, I'll give you a little clue on how to handle payer coverage of let's say the JAK inhibitor for the arthritis and an IL twenty three inhibitor for the psoriasis and they're automatically denying it and you have to do the phone call and all that crazy stuff. And the tact that has worked at least in Texas, where it's a little bit more liberal, is that you say the patient has two different diseases. The patient has psoriatic arthritis, which is not psoriasis. To assume that one magic bullet is going to treat two devastating diseases, that's horrible of you to think that, and I sometimes get away with that. I don't know any other tricks that might work there, but I think it is reasonable.

And the good news is that there are combination trials that are well designed trials that are in progress, and there are going to be more head to head trials in the future that will also help us. Again, I can strongly recommend the audience to get this figure, take a picture of it, we'll put it in the slide downloads, but to print this out and have it on your desk, it's really useful to refer to. Ben, this is your case.

Okay, thanks so much. So we'll tackle RA next with a fairly straightforward case, but with some questions to be answered.

Ben, let me interrupt you a second. I just got a late breaking question and I'm sure maybe some of you do this. Peter Trujillo asked the question, do you use ultrasound guided injections to peritendinous injections to manage dactylitis? He's tried it and it's worked really, really well. What we do know is that when you look at all the drugs that we've listed and that are on those lists, there's no preference drug for dactylitis or enthesitis.

It's going to be luck or draw. Has anybody used that number one ultrasound to manage these people or two, used local injections? Emma, do you do that?

I don't I don't do them myself and certainly we have done it within our practice. We'll often get it done under ultrasound with one of our radiologists and it does work quite well.

Interesting to note. Anybody else? Okay. All right. We're gonna move on to RA.

Sorry, Ben, go right ahead.

Oh, great. All good. Great question. Yeah, so this is a story of a 37 year old female who has a seropositive rheumatoid factor, CCP positive rheumatoid arthritis. Symptoms for six months and she's been on methotrexate orally twenty milligrams weekly, but still is having breakthrough symptoms, joint pain and active synovitis objectively on exam.

And we know from her plain film x rays of hands and feet, she has erosive changes. In a very short period of time has very damaging changes radiographically that we note. Her history indicates she's post hysterectomy and has this past medical history feature of a positive PPD skin test five years ago, negative chest x-ray, but her positive PPD was not previously treated. No other major medical problems, no other medications. So we can really focus on her rheumatic disease in this situation.

So methotrexate, moderate dose, twenty milligrams weekly with the folic acid.

So I guess the first question is on the right. If she still is, I think this goes to what Emma pointed out, which is you ask the question what they want. Are they going to get pregnant? Are they done with pregnancy? Pregnancy?

Are Are they they using birth control or whatever? But let's say though, it is a woman of childbearing potential who doesn't want to be without the option of future childbearing. Will you still use methotrexate to get control or will you avoid that and leflunomide at the outset? Ben, what would you do?

Yeah, so it really does depend on the timing of when pregnancy is hoped for, is expected. That's a conversation we tend to have very frequently and often. So it's very patient centered and very patient directed in terms of that. Certainly methotrexate we may have a lower threshold for use if someone's planning pregnancy in years that are still to come. A leflunomide may be less so, again, although we know we can wash leflunomide out, there's a process that we can use and protocols that can be used in that case.

But we're gonna have the discussion with the patient and that was really the highlight of this, bringing this forward for this patient.

Well, I think we all use methotrexate initially, but when methotrexate fails, the question is, what do you move on to? We have lots of choices here that we can use there are differences between ACR and UR guidelines. Here's the ACR guideline. If the patient doesn't do well with methotrexate, they've always endorsed the idea of moving on to another conventional DMARC. But that's not the case in EULAR, especially if you have aggressive disease.

After methotrexate, you should be going on to the most aggressive therapy. Here they take you on to whether poor prognostic factors are present or absent. Actually both ACR and EULAR have recently done away with this. Some will consider if they don't have those poor prognostic factors, rheumatoid factor erosions, many joints involved, high disease activity, extra articular manifestations, there's like five or six of them, They say it's okay, but I think really most of us are thinking now you've got to go to a combination and the combination should be a more advanced therapy than hydroxychloroquine, sulfasalazine or leflunomide. Ben, is there a situation where you would stick with the conventional DMRs as opposed to really stepping up with more aggressive therapies?

Yeah, possibly. Again, patient preference may factor into this, but I'm gonna have very long discussions, risk benefits, expectations with that patient. Maybe infection risk or history of recurrent or protracted infections might be an opportunity to lead towards triple therapy. But here's a 37 year old with aggressive disease, seropositive, erosive changes. She's affected, her function is definitely affected here.

So I'm gonna do everything I can to encourage her to utilise the treatment that we think will be most effective and joint sparing and, you know, over time.

Ben, can I ask, would you consider using Subcut Methotrexate in that initial period when this lady has been diagnosed? She's got erosions. She needs treatment fast and quickly.

Certainly

here in Australia, again, because of our funding model, we actually do need to use two DMARDs. So for a six month period. So for somebody like this, we would I would if she was not doing well on the methotrexate, we may switch to Subcut hoping to get a little bit more efficacy and we would start leflunomide, sulfasalazine or hydroxychloroquine. And again, we would have that conversation about what's happening with her fertility. She's 35, if she hasn't had children that's a huge thing to consider.

And she may have finished and in that case I wouldn't have a problem with starting leflunomide. And I would suspect she's going to need some steroids to get her through this period.

Yeah, I completely agree. I think there's opportunity to perhaps maximize methotrexate but another key point and it's really highlighted in this diamond shape here is this is a very urgent situation I would think of in rheumatology to act quickly, to be very closely observing and we need to take action. We need to take steps. We're in 2025, we have multiple arrows in our quiver to help make a difference for this patient.

So if you wanna step up your methotrexate, Emma is recommending subcutaneous methotrexate where you're gonna get a 100% absorption. I did this today in my clinic. I had a guy that was on oral methotrexate fifteen milligrams a week for seven weeks. He's 50% better, but he's still on gigantic mess. He has no money, no insurance, no nothing.

And that was my big move. I changed him, but I go with split dose oral. So split dose oral does the same as subcutaneous. So instead of being I increased him to twenty. So I gave him ten in the morning on Wednesday and ten in the evening on Wednesday.

And I'm gonna get 85% absorption just as I went to twenty sub q. He's still already on prednisone. I put him on another DMARD because it's cheap, and I'm bringing him back in a month. If not, I'm gonna have to get him compassionate use drug. Let me ask Audrey.

Audrey, what would your recommendation to Ben have been with the failure of methotrexate?

Yeah, I mean, I think kind of Emma pointed or may comment on this, you know, again, you've got a young patient here who already has erosions. And I think in that patient population, I tend to be very aggressive in those patients, unless there are some other contraindications or reasons not to use biologic therapy in those patients. I always just think, I think about how that time, we're trying to preserve that joint space. So, I would really have encouraged that patient probably to consider biologic therapy. Again, it's all about that conversation, shared decision making, what the patient prefers, if you can have that conversation with the patients about the importance of joint preservation and aggressive treatment, You know, if they had some reservations that might help them, you know, feel a little bit more at ease about that decision.

Yeah, so what would be your next step, Ben, in this guy? What you going to do?

Yeah, at this point, for all practical purposes, we'll begin talking about biologics with this patient. If we need to, we'll maximize methotrexate, say we'll add combination therapy. But I'm gonna be teeing up the patient long term through that relationship that we're developing for breast biologic approach.

We do know clearly that once you have This guy is not just severe disease, this is deadly disease. He's got all the markings of someone who has an early mortality in his future. And having erosions, the only thing that really addresses erosions really well, first are TNF inhibitors, but then all the other biologics are targeted synthetics. And then lastly, I'd say, I wouldn't shy away from a JAK inhibitor in this guy because he's young. He's not one of these people in oral surveillance that had a risk.

Let's say he had a family history of cancer or something like that, which is I think an idiotic reason to consider, he's not his uncle Louie who died of gastric cancer. It's a really remote thing that shouldn't be factored in. So on a young person, you don't even really have to worry about the JAK inhibitor equation. Anybody what's good Let's ask each of you, what's your next drug that you're adding to methotrexate that's been optimized? Emma, what's the drug?

If I didn't have to worry about funding, I would consider either a JAK inhibitor or a TNF in this woman.

Okay. Audrey?

I would probably go TNF, but I'm not opposed to using a jack. But in here where you have restrictions where you have to step through a TNF in order to get a jack.

Right. And Ben, what would you do?

Yeah, similar to what's been described earlier, I certainly would consider TNF opportunities, but JAK inhibitors would also be part of the discussion as well. We have a fair subset of patients that certainly prefer oral to an injectable weekly just for ease and such as that. So that comes into consideration also, but there's also something we have to consider here. Perhaps our next line of discussion will be about the positive PPD skin test.

Exactly. So our audience had made comments that they would use a TNF or a JAK and that's all good, mainly for the joint benefits and I would concur. But now I wanna ask you the harder question is, are you gonna do the switching within class when you fail your next choice? Are you gonna swap to another class? So are you gonna change MOAs?

Are you a one and done or you use a second TNF or a second Jack? You're either one or the other. And then I'll tell you what I am. Let's start with Audrey. Which are you, one and done or you will sometimes stay within class?

I'm pretty much a one and done. If they fail one TNF and they don't get to remission or to that low disease activity, I'm gonna change to a different MOA.

Okay, Ben, what about you?

Yeah, agreed. But the other factor I think about this, did they get any response with initial MOA, the initial say TNF. And then that might factor into my decision. But generally we're gonna, again, this is aggressive disease. We're not getting what we need controlled.

I need to go to a different mechanism.

Yeah, Emma.

Yeah, and I would be the same. I'm in a little bit of a different situation because in Australia, I can't actually prescribe these and get funding, the patient gets funding for it. So I do get to work with one of my rheumatologists on this and we'll have a discussion, but certainly we would probably switch between classes. This person needs control quickly.

So beside the issue of being a childbearing potential as a woman, the other issue is this person had a positive PPD. I have had the good fortune of working with the world's best TB specialists and looking at guidelines on this. A few things, if you're positive by one test, you're positive period, don't waste time looking for other tests. If they're positive and they come from a country where they had BCG, don't blame it on BCG. People from BCG land, TB land, who are now positive many years later are likely to have latent TB more so than BCG related positivity.

Then the question is, what will you do? It's a slam dunk. Don't use a TNF inhibitor. Use everything else. Even though you have to do TB screening for everything else or want to use a bile, abatacep, IL-one inhibitors, IL-six, that's only because they were included in the clinical trials, I would use an IL-six abatacep, a JAK inhibitor much more quickly, rituximab, IL-one inhibitors, and I would never use a TNF inhibitor if TB was in play.

But you do need to do a chest X-ray, ask about symptoms. How are you going to handle it going forward? Do you know all you need to know at this point, Ben?

I do. And Doctor. Cush, I actually have a question I want to ask about your last comment, if that's okay. Sure. I wanna attack the arthritis quickly and I wanna address the positive TB skin test quickly as well.

And the question I have, which I'd love to hear what others think is, you've got the positive TB test, we need to address that, but we also need to address treatment. What's the timing on adding that next medication with the methotrexate? I've read, I've looked at the literature, I wonder what others do in that regard.

Again, literature is made up by people who are giving you their best guess. It's below expert opinion because they're not experts and they don't know what the world's leaders in TB would say. And they taught me the following. If I had a, and this is a true story, you're gonna roll your eyes when you hear this. I had a woman that was gonna enter an infliximab trial.

She was from Korea. We did the screening visit. She's on background methotrexate. She's got 13 swollen joints. I need to get her into this trial.

I'm praying she's gonna get on the high dose infliximab at, like, ten milligrams and then maybe the five, but I'm really she comes in, like four days after we screen her so we can read her PPD and it's gigantic positive. She comes from a country where they did BCG vaccination. She was due to not just have the PPD read, but also start infusion that day. I wrote a prescription, I gave the prescription to my nurse practitioner, she went downstairs to the pharmacy, got one pill of three hundred milligram INH. We put the INH in her hand, in her mouth.

She took it, we gave put the IV in, and we started therapy. You are safe. Anyone who tells you that you need to wait a month or three months, and this is for latent TB. This woman had negative chest X-ray, no signs or symptoms, it's the positive PPD. Anyone tells you you gotta wait two months, three months, whatever, wrong.

That's not what the world's experts would tell you. And these are people from Princeton and from Johns Hopkins and from Yale. And it's a little different with someone who you think may have active disease. If they have active disease, they should stay on some kind of background RA therapy, but not a biologic. Suspend the biologic for at least three months and then restart it.

Those are the rules. If they're not on, again, your person doesn't have active disease, at where she has nothing or latent TB, as long as she's covered with rifampin or INH or some of the new combination drugs, you're able to start right away with really no risk and you would not lose. And the more important thing is, what did we lose in a court

of

law? That's the whole thing, right? And that's what leads to a lot of prescribing. That's why I threw in this slide that we talked about comorbidities with Emma and on Audrey's case that sometimes the comorbidities play a role and someone has a history of cancer or they're pregnant or they have TB or non tuberculous mycobacterial infection. There are certain drugs you don't want to use.

There are certain drugs that you can use. This is my slide, you blame me, I'll go to court for you on these slides, and this is a download that you can get this month or on RheumNow. But that's kind of what you end up prescribing. You end up backing into what may be the appropriate treatment option. So, any other questions for Ben on this case before we move on?

Ben, what did you end up going with for your next agent?

So we treated and, I believe we use abetacept or JAK for this patient, again, avoiding the TNF.

Yeah, think in someone that's doing shift work, think it's really important to talk about compliance with the JAKs. We've certainly had issues with people doing shift works, being able to take their JAK inhibitors regularly because they fall asleep on night shift and forget. So yeah, I think maybe an injectable would have been a great option for this woman.

Yeah, thanks Emma. So let me ask each of you, I can tell you no rheumatologist that I know of really spends any time really dealing with polypharmacy and or patient compliance, which are gigantic issues. Do you do this when you see your patients? Because I know that my nurse practitioner that I've worked with for so many years is so much better at this than than I am. How how do you handle those two issues, Emma?

I I certainly do, and it's it's good that you're pulling up a PMR case now because this is the sort of patient that I have the really long conversations with about polypharmacy and how they're going to dose. And it's options when I get a pharmacist involved to help package their medications. And on the flip side, for the younger patients, especially in the inflammatory spinal clinic with all the boys who've got AS, they're a younger cohort. We know that their compliance is not great. Their compliance at turning up is not great.

So we spend a lot of time counselling these patients, not only about medications, but also about their lifestyle. Can we get them to stop smoking? It would make such a big difference to them. Yeah, certainly.

Audrey, how do you handle it?

Well, I think I'll speak to like compliance. I, you know, this is something that I go through every visit with patients. You know, are you taking your medications? Are you taking them correctly? Are you taking them the amount that you're supposed to?

I'll ask patients in multiple ways during one office visit, you know, about their methotrexate and how they're taking it. You know, come to find out maybe they haven't had it refilled or they're taking it incorrectly or they're taking half the dose that they're supposed to. You know, and especially in those patients that have persistent joint inflammation, you want to make sure that they're adhering to their therapy correctly. It's not that they failed the drug, it's that they're not taking the drug the way it's supposed to be taken. So I do spend a lot of time on compliance, with patients.

Ben, last word on this.

Yes, similar push to Audrey. I remember a dear patient just a few years ago, retired, limited income. He needed a strong treatment for his rheumatoid and he just wasn't getting better. We continue to question in a very courteous and kind way. And ultimately we learned he just wasn't taking these medications because he could not get them.

So we took a different approach and ultimately we're able to help him over time. I think simply asking and building that relationship makes a tremendous difference.

You know, I always, many years ago, ten years ago, the longer you do this, the smarter you get in management. And I taped a little post it to each of my computers I worked on in front of the patient, said the same three things, hope, goals and rules. And what I do is I sometimes have to say, here's five things that I want you to do. But the most important of these five things is that you got to take the six methotrexate on Wednesday. You can't cut that corner, right?

Number five, you might cut the corner if you have to, you're giving them rules and putting things in perspective. We just think that they hold on to our every word and follow our every instruction. Boy, I know that's not true. So our last case is a PMR case. A 70 year old white male was diagnosed several years ago by the primary care doctor with polymyalgia rheumatica based on hip and shoulder girdle pain, aching, and stiffness.

There was an elevated set rate that was, I think it was greater than 80. At the time, he was given prednisone twenty milligrams. And of course, he went, skipping and jumping and ran a marathon after that because it's the best line I ever heard was when we were doing the polymyalgia rheumatica campaign from doctor Steve Paget at Hospital for Special Surgery. He used this line, he says, Giving steroids to PMR is like giving spinach to Popeye. I mean, as soon as they get it, boom, they are boundless and so thankful.

So this guy, that's exactly what happened to him. And over two years, there was the slow wean down to ten milligrams, but ten milligrams he flared, could not do well. Methotrexate was started. That looked like it might have had some promise, but the same time as creatinine, which was like 1.1 went to 1.3, went to 1.5. Methotrexate was stopped.

And when that was stopped, he even on ten milligrams, he was still with pain and stiffness and had the CRP that was elevated. And the question is, how do you manage these people? So, we can spend a lot of time, I won't spend time on what's your steroid regimen, but I think you to have in your mind a goal for steroids. I'm going to get off it within six months. I'm going get off it within eight months.

We always tell the patient, I think everyone's health, one to two years you'll be on this therapy, but eighty percent of people are on therapy for more than two years, more like five years. And the question is, if you set the expiration date on steroids, what are you going to do to get there? So does anybody have a magical formula for expectations with steroids, Ben?

I don't have a magic formula for steroid or steroid taper, but I do want to throw a bit of a curveball, Doctor. Cush here. And one of the things this case would cause me to do and our team rheumatologists, we would ensure, we would maybe do a bit more workup to ensure that the PMR truly is the primary diagnosis here. And not doubting it, we know there's resistant PMR and such as that. A 73 year old rheumatic disease may present atypically at this stage.

So I would be careful with that. Methotrexate certainly is something we're comfortable with using in this situation, but no magic potion as it relates to prednisone in this case for me. But I would ask a lot of review systems questions, maybe a little more workup just to be sure about the diagnosis.

PMR really, in my view, falls under the heading of seronegative RA. When you have a seronegative RA, you should constantly be thinking about what the real diagnosis might be. And I think that your point is brilliant. And so that wasn't done in this case, in which case, what could you have done? You could do ultrasound, a great history, another great exam.

You could do ultrasound to diagnose the tendinosis associated with that to further meet the criteria. You could spend a lot of money and do a PET scan. Anybody have another idea as to how to cinch a diagnosis? I wouldn't do genetics. They have the same genetics as RA, the HLA, Doctor, Beta-one alleles, Doctor-four, all of those.

That would maybe make you think it, but I don't know of another way other than the imaging techniques and a repeat history and physical. So Emma, your approach to steroid therapy and then when do you move on?

Well, I think if he's had over two years of steroid therapy, and you'd want to know that that taper was done correctly, you know, was he bouncing up and down? Because sometimes you see these patients, they go up to 20 and they go down to 10 and then they go to five and then of course they're going to flare. Has he been counselled correctly on how to wean this prednisolone correctly in a PMR situation? So I would, if I thought he hadn't weaned correctly over those periods, then yes, we could re trial it again, but he's also had a trial of methotrexate that hasn't helped. Of course, here in Australia, we can't get access to any of the other medications for PMR.

Don't have approvals for it to be subsidized. So we would maybe say that this person had a seronegative rheumatoid and go along that pathway to get access probably to an IL six would be our

Richard Conway from Dublin, Ireland gave a great lecture at RheumNow Live last year talking about PMR management and his schedule. Again, he's going to start usually at twelve point five, fifteen, mostly fifteen milligrams, sometimes twenty. But after two or I think it's three months, he says his schedule just to make it easy in everyone's mind is you make changes monthly and you're but you're only making changes at either two point five. And then when two point five milligram changes fail, now all changes are at one milligram.

Yeah, I listened to that one, Jack.

Yeah, I thought it was a really great lecture and I really liked his approach. And there's certainly the guidelines people, and there are no firm guidelines on this, by the way, that are recent. I think there will be recent guidelines coming up from either UR or ACR on how to better manage PMR in an era where you have now a lot of new choices. That would be good.

I think the EULA ones are ten years old now.

Yeah. I have that slide there for the 2015 is the last one. Right?

And I know they talk about parenteral, I think, also. Do they not? Parenteral what? Corticosteroids.

Yeah. I don't I don't think I can believe in that. They're they're on the list. We'll look at it later.

I I certainly wouldn't use it, but that's how old these guidelines are now.

Doctor. Yeah, because they have well, and they're so outdated and they only had steroids to play with. When they finally got down to the last bullet point on steroid sparing, it was like, and you could use methotrexate, which has been shown to be actually quite a failure. And they did that in this guy, but you got to move on. Let's see, who should manage PMR with survey done last year said we should be managing that.

That means you and I in rheumatology should be managing it. This was the guideline from 2010 where they said daily prednisone fifteen for three weeks, then twelve point five for three weeks, then ten for four to six. This is some crazy cockamamie scheme. And then over here, they have the 20, oops, sorry about that. The 20, fifteen, it's the same thing.

It's all steroids until you get down to this last bullet point. When it's methotrexate, they don't even have our current choices. So our current choices more look like this. You're going to choose an IL-six for which only ceruleanmab is FDA approved, but there are other IL-six inhibitors. Then there are other therapies that have been approved, tocilizumab and upadacitinib for giant cell arteritis, which I think it's the same disease, but extent of disease gives it the different label.

I'll go back to this, and ask Ben, what be your next choice?

Procerolizumab in this case, with the FDA approval and I think that's where I would go next.

In The United States when you have FDA approval, you can use that as the good reason and the proof that you can get a drug covered by insurance. But remember, FDA approval in The United States and other regulatory agencies, its main function actually is marketing. It's not the stamp of approval that the drug works. You can use any drug you want. But for the company to market it now, insurance companies will use that obviously as far as a justification for payment.

But you can send them the package insert for cerilumab, or you can send them 10 pages of research printouts on another IL-six inhibitor or on a JAK inhibitor as evidence as to why I can't use an IL-six inhibitor, I have to use something else. That's the way to get around that. I think there is a wealth of experience in the literature with IL-six and with JAKs, and luckily we have some approvals there that really will help therapy. But does anybody else use any other regimens here that might be advisable in the situation of difficult to manage or refractory or unweanable PMR? Audrey?

I have a few patients that have refractory PMR that I have used leflunomide, and they've done quite well. So, this might be perhaps an option for this patient who had, know, a mildly elevated CKD. If he patient wasn't interested or not a candidate for cerilumab. That might be an option.

I've done that as well. I use leflunomide. It's my steroid sparing drug of choice in polymyositis and dermatomyositis to be truthful. Of course, there's methotrexate and other drugs, but I like leflunomide. I've used it in psoriatic arthritis that's difficult and certainly in PMR.

The advantage of leflunomide in any condition, it's got an incredibly long half life. Once you get someone to a stable dose of twenty milligrams a day, I switch them over to eighty milligrams once a week, one hundred milligrams once a week, and now you just increase compliance without sacrificing toxicity. I think that really works. Emma, do you have a pearl on a case like this?

Yeah, I think we have also had experience with leflutamide in somebody like this. But I think also to say for this man, he's had a really high burden of steroid use over the last few years. His bones need checking. Need to do the whole We need to be looking after this person as a whole as well. He's probably sitting on some osteoporosis as well.

Right. I'm so glad you brought that up.

Because these are the people that are sitting ducks. Next time we see them is when they've done enough.

Because of his steroids, he's at risk for osteoporosis and fracture. He's at risk for PJP pneumonia. He's at risk for cardiovascular disease. He's at risk for infections. It is ugly and that should be the reason why steroid sparing should be certainly advocated.

That was really, really helpful. I want to everyone, I want to thank our panel for an excellent discussion and excellent cases. Next week on Tuesday night rheumatology, we'll be discussing APP controversies and misconceptions. I hope all of you will tune in and tell your friends to look at the recordings and the podcast on this. Emma, Audrey, Ben, thank you very much.

Good night. Me.

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