Tuesday Nite Rheumatology (on 11.25.25) Save

This podcast is a preview of the great lectures and speakers you'll hear at RoomNow live twenty twenty six, February seventh and eighth in Dallas, Texas. You can register at roomnow.live. In this podcast, you'll hear some of the speakers and lectures from RoomNow live '20 twenty five, specifically on RA, PSA, SPA, and vasculitis. Hope you enjoy it. Hey, everyone.

Welcome to Tuesday night rheumatology. This is where we give you the best in rheumatology. Tonight, a replay of RoomNow live 2025, where in this session, we're going to go over the pod on vasculitis. We want to thank our sponsor of Room Now Live and this pod, Sanofi, for their, support of rheumatology education. As you know, RoomNow Live twenty twenty six is coming up on February seventh and eighth.

That's going to be in Dallas, Texas for those of you who will join us on-site. Registration is now open for either on-site attendance or virtual attendance. I think you're going to love the program. I'm really proud of it. We got fabulous speakers.

We have shorter lectures, longer time for Q and A and discussion panels at every session, I think it's something you should look into. You can go to roomnow.live to register for this meeting. Tonight's Tuesday night rheumatology is a replay of RNL twenty five, the vasculitis session or pod. We have three great speakers, Doctor. Michael Wexler, a pulmonologist from Denver, talking about the management of EGPA in 2025 and beyond.

Doctor. Rene Ray, who comes from Penn, is going to talk about imaging in patients with vasculitis. Doctor. Richard Conway from Ireland is going to be talking about modern treatment of POTNR. Again, you can go to roomnow.live to register for our next meeting.

Let's get into our first segment. This is an excerpt from Michael Wexler's talk on the management of EGPA. Doctor. Wexler is a professor of medicine at National Jewish in Denver, Colorado, and a world expert on EGPA. Was blown away by his talk.

I think you will be too. Take it over, Michael.

In terms of management, there's been a huge evolution in how we manage EGPA just in the last six or seven years. And this has evolved significantly with development of new monoclonal antibodies. Historically, the management of EGPA was steroids, steroids, and more steroids. And the purpose of the steroids given at one to two milligrams per kilogram per day was to really inhibit eosinophil colony growth as well as cytokine production and reduce eosinophil survival. And steroids alone were effective in about ninety percent of patients.

But the problem is that when people were taken off corticosteroids, the disease would recur. And very few patients could get off of steroids. In fact, in one of the pivotal studies which we did with mepolizumab, the control group, only three percent of patients could get off of corticosteroids. Furthermore, not all patients responded to steroids initially. And there are all the side effects of steroids that you're familiar with, everything from thinning of the skin to osteoporosis to cataracts and glaucoma and neuropsychiatric issues.

So as you all know, steroids are good, but steroids are bad. So we want to try to avoid them. So who could get steroids alone? Historically there's a French vasculitis study group. And they said that those with the least severe disease or what they call the five factor score.

If they had no kidney involvement, GI involvement, cardiac involvement, or CNS involvement, they could get steroids alone and they'd do fine. But the relapses would occur at lower doses. And so they recommend that you need to taper slowly. So in general, what does one do if the patient relapses on a low dose? I usually just bump up the dose of the corticosteroids and see if I can get them back down afterwards.

But if steroids alone don't work, we need some kind of add on therapy. And sometimes steroids can't be tapered at all and so you need some kind of step down therapy. Historically what's been utilized is drugs like cyclophosphamide, azathioprine, mycophenolate. Imatinib has been utilized for that myeloproliferative variant. Rituximab has been utilized in a subset of patients.

But what are the data? Well the problem is that there were almost no trials in EGPA. It's a rare disease, there were only case reports, case series, and anecdotal evidence. And some of the recommendations were based on other vascularities or on asthma. And so there were some older trials looking at methotrexate in asthma.

Or azathioprine in asthma. And so people made some recommendations based on that. This is a good example. And a lot of rheumatologists reflexively recommend cyclophosphamide and or azathioprine. But this is probably the best data of azathioprine EGPA.

And it comes from this paper from 2017 in which patients were all lumped together with EGPA, with MPA, and PAN. And they gave them azathioprine on top of standard of care. And what they found was there was no significant benefit of azathioprine in terms of the key outcomes of relapses or corticosteroid utilization compared to placebo. So azathioprine added on to corticosteroids had no decrease in treatment failures, no decrease in relapse rate, no decrease in steroid use, and also no improvement in the asthma symptoms. So while azathioprine is often utilized, the data for its utilization in EGPA are pretty slim.

What about rituximab? Well rituximab, as you know, depletes B cells. It's been utilized and approved for GPA and MPA. But really, again, are no significant data in eGPA. There's been a couple of case series which have shown improvement, eighty eight percent improvement at twelve months in some cases.

Forty nine percent of patients got into remission, but only six percent were able to discontinue corticosteroids, which is similar to the placebo arm in the MIRROR study, which I'll talk about, where only three percent of patients were able to get off of corticosteroids. There were some improvements in some of the asthma and ENT manifestations, and the thinking is that it may be more effective in ANCA positive patients. But again, we don't have good data. There's a study going on now in France where they're evaluating it compared to standard of care. So what about targeting eosinophils?

It's the E of EGPA, we think that eosinophils play an important role. There are many potential targets on eosinophils. You can target IL-five or the IL-five receptor. You can target Siglec eight, which is a sialoprotein on eosinophils, EMR one, chemokine receptor three, CRTH two, which is the prostaglandin D two receptor. People have looked at all these in asthma, but really it was IL five, which is the key cytokine that's responsible for eosinophil maturation, proliferation, and survival that has been the main target.

And our recognizing this, and meplizumab was the first anti IL-five therapy. It was approved for asthma in 2015. And we did a study that was published in the New England Journal of Medicine in 2017, where we compared meplizumab to placebo for patients with relapsing or refractory EGPA. And what we found was that EGPA resulted in significantly increased time to first relapse compared to placebo. And patients were allowed to, as long as they were on seven point five milligrams of prednisone or more, they could be on azathioprine or mycophenolate or methotrexate as well.

And so we found despite that, was significant benefit in terms of relapses. In terms of the number of relapses, we were able to cut the number of relapses in half from around two point three per year down to one point one four per year. And the proportion of patients who achieved remission, which we defined as getting down to four milligrams of prednisone or less and having a Birmingham Vasculitis Activity Score of zero, was achieved in a greater proportion of patients with meplizumab compared to placebo. Very few patients in the placebo group were able to achieve remission. Importantly, corticosteroid dose was basically cut in half as well in this patient population.

Patients treated with placebo started off around ten milligrams a day, in the blue line, and ended up at ten milligrams a day by the end of the year. Whereas patients treated with meplizumab started off at eleven milligrams of prednisone and got down to about five milligrams a day. And fifty seven percent of patients treated with meplizumab were able to cut their steroid dose in half, compared with only twenty one percent in the placebo arm. We did some post hoc analyses to see what other benefits, not just achieving remission, but if we looked at the proportion of patients who were able to either get in remission or have a fifty percent reduction of corticosteroid dose, or be relapse free over the course of a year, we found that seventy eight percent of patients treated with meplizumab were able to achieve at least one of those outcomes versus only thirty two percent in the placebo arm. And when we were a bit more less conservative with the definition, used the definition of seven point five milligrams of prednisone, eighty seven percent of patients treated with meplizumab, anti L5 therapy, were able to achieve remission.

So nine out of ten patients basically. And these outcomes were independent of immunosuppressant use, independent of disease duration. Whether it was clinical benefit overall, no relapses, fifty percent reduction or remission, there was a significant benefit with meplizumab compared to placebo. And this was also independent of all patient categories. Whether patients had a history of positive ANCA or not, whether they had a BVAS of zero or not, whether they had a vascular damage index score that was elevated or not, there was significant benefit with meplizumab.

And meplizumab improved both the asthma symptoms and relapses as well as vasculitis relapse. This is a question that often comes up. Does meplizumab prevent vasculitis relapses? So that's meplizumab. What about other anti IL-five therapies?

So we did a small study with rezlizumab, which is an IV preparation. And we gave it to eight patients with EGPA. We were able to reduce steroid dose from seventeen and a half milligrams a day down to eight milligrams a day. Six of the eight patients were able to get down to five milligrams a day or less, and three patients came off of steroids and also reduced exacerbations. We did a few studies with benerolizumab, which binds the IL-five receptor.

This was a study where we gave benerolizumab five doses over the course of twenty four weeks. And we got patients from fifteen milligrams down to two milligrams. Five of the 10 patients came off of steroids, and we reduced exacerbations from 4.6 events per year down to 1.5 events per year. This led to the Mandara study that was published in 2024. Again, published in the New England Journal of Medicine.

And this was a head to head non inferiority study comparing benerolizumab thirty milligrams a month, to meplizumab, three hundred milligrams a month. You should know that both those therapies are approved in asthma, but at lower doses. For benerolizumab, it's thirty milligrams every other month, and meplizumab, it's one hundred milligrams a month. So we compared these two doses in patients with EGPA. And we found the proportion of patients who were able to achieve remission was very similar between the two groups.

Fifty eight percent or so, fifty nine percent of patients in both meplizumab and benralizumab were able to achieve remission. When we looked at the proportion of patients who were able to get a BVAS of zero by the end of the study, It was similar, around eighty three, eighty four percent. And the proportion of patients who were able to get down to four milligrams or less per day was also similar, around sixty percent. So this study met its primary endpoint. And benerolizumab was deemed to be non inferior to meplizumab.

And it was approved by the FDA for the management of EGPA in September of this past year. It was also approved based on the fact that the remission was similar. What was interesting was in this study, the Mandara study, the proportion of patients who achieved remission was much higher than in our prior study, where with meplizumab only thirty two percent of patients were able to achieve remission. Now, for whatever reason, fifty six percent. Probably because more physicians felt comfortable tapering steroids and getting people into remission.

Another important component was the proportion of patients who were able to reduce corticosteroids. So with benralizumab versus meplizumab, over seventy percent of patients were able to cut their steroid dose in half. But when we look at one hundred percent reduction in steroid dose, forty one percent of patients treated with meplizumab were able to get off corticosteroids. Twenty six percent of patients with meplizumab were able to get their patients off of steroids. This was associated with the greater reduction in eosinophils that was observed in patients treated with benralizumab down at the bottom compared to meplizumab.

Again, they got down to low dose of meplizumab, but even lower with benralizumab, and that might be associated with that reason. The problem with all these anti IL-five data, there are no data in acute disease. But frankly there are no data for acute disease with any drug in EGPA. We also don't have such long term data, although we published recently seven years of data with meplizumab in EGPA, long term safety and efficacy. And there's been this question about the role of, in ANCA, in non eosinophilic vasculitis components of EGPA.

Again, benerolizumab was just approved in September, meplizumab was approved in 2017. And there are other therapies like rezlizumab which are still in development. Just in terms of EGPA treatment basics, remember bronchodilators treat the asthma, inhaled steroids, leukotriene modifiers are fine as well. They're not as bad as we once thought. And then just do prophylaxis for infection, bone loss, peptic ulcer disease, and give flu, pneumonia, and COVID vaccines.

So just to summarize, EGPA is a complex syndrome characterized by asthma, eosinophilia, sinus disease, pulmonary infiltrates, neuropathy, and vasculitis in one or more end organ. The eosinophil is central to EGPA pathophysiology. It can be challenging to treat, but if you treat aggressively you should do fine. Therapies are needed to induce remission. Steroids are effective for many patients, but they are associated with significant side effects and toxicity.

And you can use these biologic agents for steroid refractory disease, for step down therapy and to prevent relapses. Mepalizumab and benralizumab are pretty equivalent to one another. They facilitate corticosteroid withdrawal. So you should use biologics for these relapsing refractory patients. And both neplizumab, benerolizumab are okay.

We're in the middle of a study looking at depamokumab, which is a twice yearly anti IL-five therapy. So now I boldened the anti IL-five as part of this treatment regimen. That should be, you know, as part of the EULAR recommendations, it's considered to be one of the key choices for patients with EGPA. So thank you so much.

You, Doctor. Wexler. That was great and underscores the fact that we as rheumatologists probably need to co manage these patients with EGPA with our pulmonary colleagues. I think it's probably the best, to have both worlds involved in that one patient. Because again, you make the decision on this an eosinophil pulmonary issue that's going on right now or is it vasculitic?

When is a biologic and which biologic is going to be most appropriate? I think this was a really helpful lecture. Our next speaker is Doctor. Rennie Ray from Penn Vasculitis Center at the University of Pennsylvania. She's going to talk about imaging and vasculitis.

I loved this lecture.

That in all patients with giant cell arteritis, we should be screening for large vessel or extracranial involvement. The prevalence varies based on the study, but can be as high as twenty five percent of cases. These patients can have involvement of the aorta and its primary branches, like the subclavian and common carotid arteries. And really, a large proportion of patients with large vessel GCA will have involvement of the thoracic aorta and may develop aneurysms, which are associated with a higher risk of mortality in GCA. So very important to identify these patients early on.

Initial assessment generally tends to be with CT or MR angiography. What we're looking for is diffuse and circumferential wall thickening. We're also looking for areas of arterial stenosis, especially in those branch arteries. What we tend to see are those smooth tapering lesions in long segments of the artery. This is in contrast to ather atherosclerosis, which tends to be more focal and eccentric.

We also, of course, look for aneurysms, usually in the aorta. CT has a few advantages. Speaking with several radiologists, they really like CTs because they have better resolution. They're also shorter scan times, so they're less prone to motion artifact, and they have lower cost. However, MRA is also equally good, especially if there's a contraindication to CT, and it has added the advantage of not having any radiation.

So all of the major guidelines recommend screening for extracranial disease, but there are slight differences in how they approach this. The American College of Rheumatology gives no preference. In Europe, the EULAR guidelines, they use a lot of ultrasound. It's more widely available there. And when they do initial ultrasound, they get temporal and axillary artery.

Their next favorite modality is actually a PET CT, which they recommend over MR or CT. I like the British Society of Guidelines. They also have no preference, but they give a little bit more of a nuanced discussion. They recognize that ultrasound cannot assess those deeper arteries, again that aortic aneurysm that you don't want to miss in these patients. And PETCT has less anatomic detail compared to MR and CT, but it can also identify some alternative diagnoses such as malignancy and infection.

So my initial approach in extracranial screening in GC is usually to start with a CTA of the chest, abdomen and pelvis. Again, better resolution, can evaluate deeper arteries unlike the ultrasound, shorter image acquisition time, lower cost, and also can identify calcific atherosclerosis, which is common in these older adults. If that baseline is abnormal, it may not change your treatment immediately since you're already treating them for cranial GCA, but it may impact your decision to continue long term monitoring. PET CT would be great for identifying early vascular inflammation before those structural changes occur. It's just more costly and therefore can be a little bit more difficult to get.

So moving on to our next case. And are showing up in your online poll? Oh, okay. Oh, darn. Okay.

This one did. Okay, great. Let me just see what happens. Oh. That's okay.

Well, you guys here can think about it in your head. So this is a case of a patient with polymyagia rheumatica who has been on prednisone, two milligrams a day, doing well, stable, no symptoms or signs of GCA. And which of these studies would you perform next? And I kind of already gave away what I would do, which is I really wouldn't do any of these at the moment with a caveat. And so subclinical GCA, not surprisingly, is can be seen in PMR.

In this meta analysis, they found around twenty three percent of those with PMR have subclinical GCA based on either biopsy, ultrasound, or PETCT. The tricky thing, though, is what are you going to do with that information? And it is really unknown if screening for GCA is going to change long term outcomes in these patients. You know, for example, if you think about it, if you were to get if you had a patient with PMR who got a temporal artery ultrasound or biopsy that was positive but they're asymptomatic, how is that going to change your treatment right then and there? It's not clear whether it should or will.

So at the moment, I do not necessarily I don't think this will necessarily change your management. The only exception are those aortic aneurysms, which we do see. We do see large vessel disease with PMR in the absence of cranial symptoms. And this, again, is a life threatening comorbidity. We, at Penn, we're at a center where there's a high rate of thoracic aortic aneurysm repairs being done.

It's a referral center. And so these patients, after their aneurysm repair, end up in my office after they identified on pathology this patient had aortitis. And when you go back in their history, not uncommonly, there's some evidence that they've had PMR that was undiagnosed. So my approach at this moment with the current data available, but certainly further research would be needed, is to get an echocardiogram in these patients just to assess the aortic root and ascending aorta. And in these older adults, most of them have had an echocardiogram in the recent past, and many of them at some point have had some type of cross sectional imaging, whether it be CT or MRI.

And so I can go back and review that data and make sure there's no major structural abnormalities in the aorta. Our next case is a case of Takayasu's. So this is a 48 year old woman who was referred after just a routine healthcare evaluation was found to have an absent left radial pulse. And this led to an imaging that showed diffuse wall thickening of the aorta. Other medical history was notable for chronic kidney disease with an eGFR of 20 and claustrophobia.

Which of these following vascular studies would you perform next? And I'll just let you think about it and what you would answer. So I will say, of course we would normally start with a CT or MRA. I was trying to push you towards this answer, is the PETCT. With the EGFR of 20 we've got to be a little cautious with the CTA, with the contrast.

And with claustrophobia, MRA would be more difficult. And there's other reasons why in this situation a PET CT potentially could be very helpful. So it continues to be a very challenging issue of distinguishing active vasculitis from vascular damage or atherosclerosis in both the clinical management and in clinical trials of large vessel vasculitis. And I think of this like x rays and rheumatoid arthritis. When we see erosions, that helps identify this patient has had inflammatory arthritis.

But whether they have active synovitis today that requires immunosuppression is not clear. And it's the same situation with this vascular imaging. So what we try to look for is interval change. Are there new or worsening lesions that would be indicative of an ongoing active inflammatory process? Of course this requires that they've had more than one time point of imaging.

If possible, if they've had prior images, I do go back and pull that imaging data and I ask a radiologist to compare side by side and look more closely at the vasculature. Oftentimes, sometimes they don't comment on the vasculature, they're more focused on some other issue at the moment. And it's also important moving forward that we are getting serial imaging and establishing a new baseline after treatment. If we're only getting imaging when they flare, we're going to miss what the changes occurred during remission and we're not going to be able to see or identify that interval change. Now the challenging thing is that changes don't necessarily always indicate vasculitis, sometimes simply due to vascular remodeling, plaque development at a site of an old vasculitic lesion, or increasing sizes and aneurysms just a result of hypertension or other issues may be explaining the underlying changes.

And so this is where potentially I think PETCT could be very valuable in providing some additional information that's complementary to our CT or MRAs. Now PETCT has contrast that is radio labeled glucose, And at sites of inflammation, that glucose is preferentially taken up and will show as hypermetabolic areas of activity on the PET scan. So we have taken a tool in the oncology realm and repurposed it in rheumatology, which obviously sounds familiar. But there is a slight difference in how it should be done in vasculitis. Ideally, we want to wait a longer period of time between contrast and image acquisition.

And studies have shown that if you wait at least two hours and even three hours, that was shown in an ACR abstract this year, that it will improve the sensitivity because it gives more time for that uptake into the vessel walls and also more time for the contrast to leave the circulation so you can see that vascular metabolic activity. PET CTs are also affected by glucocorticoids. We ideally want to get these when patients are in lower doses of prednisone. And we still see persistent vascular uptake in the walls even during clinical remission. Remission.

So kind of the longitudinal use of this is still unclear. Here are some examples of PET CTs in a patient with large vessel vasculitis. This is a coronal view, so we're looking at the patient head on. And you can see all of the hypermetabolic activity in the aorta in both of these images. And also you can see it in the subclavian arteries that go to the arms and the common carotids in the neck on the figure on the left.

This next case is a case of a man with aortitis, which was found incidentally and then underwent surgical repair with the pathology showing granulomatous inflammation. He's otherwise abnormal with normal acute phase reactants. And which of these vascular studies would you perform next? Oh, there we go. Okay, great.

Interesting. So a good majority want to get a PAD CT, and the rest, you know, suggesting CT or MR angiography. So I agree. I would definitely start with initial surveillance, looking for structural changes. But I also think this could be an opportunity to get a PET CT.

We, again, at our site we see quite a few of these and we've done some retrospective studies where we've looked back to see if there's anything on the radiology, on the imaging that can predict who's going to have aortitis after surgical repair. And there really isn't. There really is no good way of distinguishing these patients. There's a small percentage, maybe less than ten percent, who had some wall thickening that was more suggestive of aortitis. But majority we have a difficult time distinguishing.

So PETCT could be very useful if you want to identify early vascular inflammation. Also just a reminder that besides giant arthritis, Takayasus, there are other conditions that can cause aortitis, including Kogan's, relapsing polychondritis IgG4 related disease. So asking them about those other manifestations that help might point you towards one of those diagnoses would be helpful as well. If these patients have either a normal CT angio, the rest of their vasculature is fine, and or their pet's CT is cold, I don't treat these patients. Because many times they've had this disease, it's been longstanding for many years, and it hasn't spread to other sites.

And the goals of immunosuppression and chronic immunosuppression can be very unclear. So just to summarize, I didn't get a chance to talk about pulse volume recording segmental pressures, but there is a slide on that next, and certainly some things to think about. But that is more for looking at distal arteries and the arms and legs. CTM or angiography are looking for structural changes, the sequelae of vasculitis. PETCT looks more for metabolic activity and therefore can identify early ongoing vasculitic inflammation.

CT has slightly better resolution than the other modalities. And then there are a variety of other differences across these imaging modalities that may push you towards one tool versus the other, many of these being very complementary. And I will, for the sake of time, just kind of skip through this, but certainly something you guys can read about later. So in summary, a suggested practical approach to imaging large vessel vasculitis is to consider screening initially with a CT angio. Again, is better resolution.

It's cheaper. It's faster. MRA is also a great alternative if there's a contraindication to CT, or if you want to avoid radiation. I think some of our younger Takayasu's patients who have many, many more years of imaging may switch I tend to switch to MRA. PET CT could be useful for very specific situations.

And I give just a couple of examples of these, but just really in terms where it's really unclear whether there is ongoing active vasculitis based on the initial imaging and you want just more information to help guide your treatment decisions. We didn't talk about ultrasound, but ultrasound is still very useful for specific arterial territories. The ascending aorta echocardiogram can be useful If you want to assess the axillary carotid or the renal arteries, ultrasound has much better resolution than CT and also can look for blood flow. And then post volume recording segmental pressures, these are usually done by the vascular lab or the vascular surgeons. It's what they traditionally do for peripheral arterial disease and can be useful for monitoring more distal arterial, involvement.

Thank you, Doctor. Ray. The rules are changing on how we do our imaging in GCA. Similarly, I think the rules are changing on how we manage PMR. For that, we've asked Doctor.

Richard Conway, who's a consultant rheumatologist at the St. James Hospital in Dublin, Ireland, to talk about the modern management of polymyalgia rheumatica. Listen up.

So these other agents which have been available to us, so methotrexate and leflunomide, that is what many of us have used in the past in refractory polymyalgia. More recently we have the two interleukin six inhibitors, tocilizumab, sarilumab, and there's some data for rituximab, JAK inhibitors, secukinumab even. And we'll talk a little bit about each of these. So methotrexate. This is a study presented at ACR this year.

I'm sure most of us have seen this. This is from The Netherlands, with Bullhaus and colleagues. I love this study. It's small, it's 56 patients, but it's a double blind randomized controlled trial. It took exactly the right patients, new onset polymyalgia rheumatica, studied them for a year and thankfully gave them a proper methotrexate dose.

So many of our studies in diseases other than rheumatoid arthritis have been blighted by people giving ten milligrams or fifteen milligrams of methotrexate, which is just a baby dose, but it's not what many people need in clinical practice for any disease, and I think especially so for something like polymyalgamatica or vasculitis, you need a proper dose if you hope for it to help. So they use the proper dose here. And I mean, a picture paints a thousand words, that figure is showing absolutely no difference to methotrexate or no methotrexate. So I'm convinced by this study. I think methotrexate does not work for polymyal dermatica.

I think probably what we saw in the past where it worked with individual patients, maybe. So some of it is probably just that they got better anyway, irrespective of what they were on. Some of them probably had rheumatoid arthritis, as we know, methotrexate works very well for rheumatoid arthritis. There are other studies of methotrexate going on, especially the Sterling PMR study, but based on this I am not using methotrexate anymore for polymyalgia. I think this is good data, it's very convincing.

The time has come to stop. Neflunomide does have its advocates who have proposed that it may be a good option, may be better than methotrexate potentially. I don't buy it. I think methotrexate and neflunomide, yes, they're different, but they're very similar and the same sorts of things tend to respond to both of them. I cannot envisage a disease where methotrexate does nothing being very well treated with leflunomide.

It just does not make sense to me. Again, we will have some more data on this in the coming years, but I'd be shocked if lefluromide proves to be the answer. And then we do have medications that we use for other diseases which have been shown to work for polymyhydramatica. So this, we're probably all familiar with this now. This is the SAFIRE study of sarilumab, big study, over 100 patients, double blind.

If you look at the bar chart, think it's not actually that impressive. It's 28 versus ten percent in sustained remission at week fifty two. But I think it is, and it's a really positive trial. It's a very good success rate, you have to remember some things about this study before you say that these results aren't great. The first is that these were not new onset patients.

These were old patients. They had relapsing refractory polymyalgia rheumatica. The second thing is that the steroid was not the same in both arms. The cirilimab patients got fourteen weeks of steroid versus fifty two weeks, I mean, that is night and day, completely different ballgame between steroid doses. And the final thing is the same issue that's happened in the JAKTA study, that the definition of remission here is incredibly stringent and that reduces the raw numbers but not the relative benefit.

So I think based on this, this is a very convincing study for sarlimab. We also have data from tocilizumab. I'm only going to show a couple of these, quite a number of studies now coming along in tocilizumab. This is PMR spared, this is a nuance at PMR, relatively small study with relatively short steroid taper again over eleven weeks, giving tocilizumab versus placebo and really good results, around sixty percent with tocilizumab in remission compared to seventeen percent with placebo. So very convincing for new onset PMR.

Another study from JAMA, from Durishal Pencek et al, this was dig a bit to figure this out, but these were really refractory patients. They had a duration of twenty months and were still stuck in ten milligrams of prednisolone. See that very much in fibromyalgia, but they found enough of them with this and gave them IV tocilizumab. And again, really impressive response rate, sixty seven percent versus thirty one percent, and nearly half of glucocorticoids compared to twenty percent. So, yeah, that's very convincing data for me for tocilizumab.

And I've already had an argument with somebody about this issue of sarlimab versus tocilizumab, with my argument being that they're both interleukin six inhibitors. I don't envisage that they're going to be any different, and say what we want about approvals and reimbursement or whatever, a Surinamev study might be a little bit bigger and a little bit stronger, but again, I can't anticipate a situation really where cirilimab is going to be substantially better than tocilizumab for polypalgia. And this is important because there are a number of issues with picking one drug over another drug. Serilumab is not available everywhere. Where I work, we have no Serilumab because of commercial decisions.

Even where it is available, with biosimilar tocilizumab, it is liable to be substantially more expensive than dolcelynavir. So in my opinion, the interleukin six inhibitors are the same. If there's a particular reason where you're based to pick one or the other, pick it rather than focusing and getting too deep into evidence based medicine, gone mad and saying, Oh, this study is slightly better, so we should do this. This was probably one of the most surprising studies that's ever been done in fibromyalgia. Was This showing that rituximab, a single dose of rituximab seems to work, seems to help.

It's the Bridge PMR study. So single dose rituximab at the start, mainly in new onset, there were a few relapsing patients, but it didn't seem to work in them. And they did better if they were given rituximab. That kind of challenged our hypotheses about how polymyalgia happens and what the pathophysiology is. I haven't given anyone rituximab for polymyal tramadica, I'm not sure it's something I have much appetite to do.

I don't think these results are as impressive in many ways as the IL-six results, but it is there. It does exist, there is data supporting its use, so it is a potential option. JAK inhibitors. So I would say a priori JAK inhibitors work. Of course they do.

They block in glucan six. How could they not work for fibromyalgia? And we do have data to support that now. And these are interesting studies in the way they were designed. So the Bachelor study of baricitinib, very recently been published, also presented at ACR last year, double blind randomized controlled trial of baricitinib versus nothing.

No steroids in either group. They could escape the steroids if they failed their placebo order baricitinib. And very impressive results, seventy eight percent with baricitinib versus thirteen percent with nothing. I suppose it doesn't, the nothing is always an issue because nobody is going to treat balmiazide with nothing, but I still think seventy eight percent is a very, very impressive response rate. The similar enough study called EAST PMR, which was a couple of years ago now, of tofacitinib, essentially of tofacitinib versus steroid and showing that they were equivalent in new onset polynalgia, and there's been another couple of tofacitinib studies as well.

So kind of quite exciting JAK inhibitor data, quite small studies, quite early data, hard to know how best to use them, whether this against nothing should be the way or whether we should be using some steroids in combination with them. So going back to this regime, I think in an era where we are considering using other drugs, that this is probably too slow. If you're in a situation where you're using glucocorticoids and you're tapering them and you're waiting for them to fail, to start something else, you probably shouldn't be sticking to that year long regime because they're going to get a lot of side effects by the time you figure that out. I think it's a very strong argument for having a discussion with the patient at the start. And if the plan is that relapse will result in the starting of another agent, then you should speed up this glucocorticoid taper.

At the very least, you should probably speed it up by half, and that is probably what I would do. So do two weeks in every dose instead of a month, and try and get an answer quicker for these patients. I think there are some other important things, and sometimes these are more important than what we actually do with steroids, that should not be forgotten with polymyalgia matica. So bone protection is a big one. People get tied up in lots about this.

Go on with the ACR, glucocorticoid induced osteoporosis guidelines and trying to figure this out. Just makes your life easy. Patients with polymyalgia, same for joint cell arthritis, if they're on glucocorticoids, ninety nine point nine percent of them are going to warrant a bisphosphonate. It is much better that they're on it than not being on it. Just put them on it while they're on the steroids.

A calcium vitamin D, if they need it, it's less important. It's usually the bit that gets done, they get their calcium, but not their bisphosphonates, and that's just pointless. They need the bisphosphonates to prevent bone loss. Please get them a DEXA scan. It is not particularly relevant while they're on the steroids and bisphosphonate, but it is a great opportunity for opportunistic screening to see if they have osteoporosis and do they need to stay on the drug after they stop the steroids.

Not everyone needs a proton pump inhibitor, but it's usually better to give them, but you don't need somebody having a hemorrhaging stomach ulcer or something else unpleasant. It's very important to encourage patients to maintain physical activity. Often their natural in clinicians to do the opposite. They're sore and stiff, so they do less, which is counterproductive and very bad in the setting of giving somebody decent chunks of steroids that they will get a lot of muscle wasting weakness because of that, unless they maintain you can be remunerated to some extent by maintaining physical activity. Many patients need physiotherapy to target specific issues.

Patient education and repetition constantly informing them of the important aspects of polymyalgia. What it is, what to watch out for, how it's treated, what to do with the glucocorticoids, what to watch out for in terms of potential giant cell arthritis symptoms, because as you know, twenty percent of patients do ultimately get that, and to contact you immediately if that's happening or if they're having a relapse is absolutely crucial. So some of my colleagues will probably get annoyed at me for saying this, but I think these patients need to be seen frequently by a rheumatologist. I think putting polymyalgia rheumatica back to primary care once you've made the diagnosis is wrong. I think as rheumatologists, we actually have a lot more to offer these patients, even than something like rheumatoid arthritis, where the treatment is very algorithmic.

We kind of go through set steps, at least until we get to very advanced stages. For polymyalgia, there's a huge amount of art and experience still in the diagnosis and management. So I think these are the very patients you should be seeing. I see them usually a month after the diagnosis and then every three months and then immediately if they have a relapse. And yes, many of those three month appointments, not much is going on, they're doing well.

But that's easy. They come in, it's a five minute appointment, check and make sure they're not flaring, that their bloods are okay, that they're doing the right thing on the steroids, that they don't have giant cell arthritis, and they're on the way. They fly through their clinic. But I think it's crucial for the times that they're not doing well, that they come in and they said, Oh, I didn't want to call you and I wouldn't have called you, but actually I'm having an increase in stiffness for the last few weeks. And if it's for the last few weeks, then great, you can fix that relatively easily.

If you have them on a six month or a year appointment and they come in and said, I've been bad for nine months, you're back to the start. You're completely wasted everything you've done up to that point in that situation. Frequently, patients have increasing symptoms as they reduce their steroids. Some of those symptoms are due to flare. Not all of those symptoms are due to flare or relapse.

And it can be very difficult for patients to figure it out. It can be very difficult for us to figure it out. So how can we expect patients to know what it is? And a steroid myopathy can seem very similar to polymyalgia symptoms, or Taylor cuff tendinopathy, gluteal tendinopathy coming because of steroid related muscle and tendon weakening can seem very, very similar. But most of the time with enough experience of seeing these patients, we can disentangle that.

Steroid related adverse events, especially with traditional steroid regimes, are part and parcel of what happens. And it's really important to see patients to try and minimize and deal with them as appropriately. Prescription mistakes either it says, because the patient may have misinterpreted something or because the pharmacy has given them the wrong dose. Unfortunately, they do still happen. They can be minimized by strategies such as I proposed, which you can't completely quit.

So time can be a great diagnostic tool in polymyalgia, and it can change your management. And the only way to know that is by seeing somebody frequently. And it's important to dispel myths the patient may have. Tell them that the polymyalgia doesn't burn out again. Tell them that the steroids, yes, they are causing side effects but we can get off them, tell them that not every flare needs to immediately increase their steroids, or hear all sorts of things from patients that they've heard from their friends down at the golf club or the tennis club.

And it's important just to keep people on track with this and that they're following your advice and not something some of their friends have told them. So what do we do? How do I manage polymyalgia rheumatica at the end of the day? So for new onset polymyalgia rheumatica, I still give steroid monotherapy. I discuss with the patient about what our ultimate treatment goal is, what we will do in the case of relapse, how happy they are doing a weekly injection with tocilizumab if we use that as an alternative.

And based on that, I'll either give them my standard year long taper or I'll give them a quicker taper. And I think that's a very reasonable place to be. I would say still, in my experience, most patients will opt for the longer steroid taper and that's fine. But there are some who do favor a shorter taper because they've experienced all of our inherent dislike of glucocorticoids. If somebody has PMR and relapses, yes, we allow one or two.

You can move the steroid up and come back down. But if it keeps happening, I think to some extent, only sensible game at the moment is to add an interleukin six inhibitor. That's what we should be doing based on the data we have. There are some patients that if the steroid dose is low enough with that kind of nebulous number of maybe five or less, the lower the better, or if they just do not want an alternative medication where maintenance steroid can still be acceptable. I showed some of the numbers from the trials and the trials would suggest that actually many patients fail tocilizumab, but I think just like with giant cell arthritis, we're not really looking at response rates of twenty eight percent or fifty percent or sixty percent.

Tocilizumab response rates for polymyalgia are probably ninety percent plus, just like they are for giant cell arthritis in the real world. So if they relapse on the interleukin-six inhibitor, check adherence because that can be an issue, and you can consider other agents with probably, at the moment, the most likely candidates being interleukin-seventeen inhibitors, secukinumab is in a phase three trial at the moment called REPLENISH, and may well be an effective agent that data that much longer, maybe a couple of years before we have it. And there is preliminary data and a hypothetical rationale for JAK inhibitors. So they're certainly an option too.

Thank you, Richard. That was great. This is our final episode of our RheumNow Live twenty twenty five replays. I hope you enjoyed this recording and the last three. I think that they were really informative and thanks to our speakers.

I want to thank our sponsor for this session, Sanofi. If you'd like to learn more about RoomNow Live, go to roomnow.live where you can register for our 2026 meeting which is coming up. Hope to see you there.