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Hello everyone. Welcome to Tuesday Night Rheumatology.
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This special edition of Tuesday Night Rheumatology.
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I bring together experts in lupus and cutaneous lupus because that's what we're discussing — advances and challenges in both cutaneous lupus and systemic lupus.
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I'm joined today by Drs. Worth, Delara, and Merola.
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You might have noticed that this month we sent out a bunch of survey questions and we wanted to send three weekly surveys to help inform our discussion.
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So I want you to know that this activity has been sponsored by Biogen, but they had no input into the questions or the panelists that we have here.
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That's pretty much up to us and to you. We want to thank Biogen for their support.
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I want to begin by number one asking you the audience to please have input by asking questions.
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Click on the Q&A box and you can ask your questions.
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We'll answer them throughout this one-hour Tuesday Night Rheumatology session.
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I'm going to ask our expert panelists to introduce themselves.
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Let's begin with Victoria. Yes. Hello. So I'm a professor of dermatology at the University of Pennsylvania, and I have a secondary appointment in rheumatology and I see lots of lupus patients.
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Victoria is very well known in the lupus and cutaneous lupus community.
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Maria. Yes. Hi everyone. Maria Dall'Era and I'm the chief of rheumatology at UC San Francisco with a specialty in lupus.
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It's great to be here. Excellent. And Joseph.
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Hi folks. Joe Merola. I'm a rheumatologist and dermatologist.
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I'm buffering I think between Maria and Vicki today.
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And I'm the tiebreaker. And I'm delighted to be with you all.
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I'm the chair of dermatology, professor of dermatology, and professor of medicine rheumatology here at UT Southwestern in lovely Dallas, Texas.
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And I'm also the president of Vicky Worth's CLE fan club.
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She's a longtime mentor and I'm thrilled to be here. As we all should be.
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Joe has been very much involved in major clinical trials in rheumatology and dermatology, including cutaneous lupus.
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And Maria has been really very involved in the ACR guidelines for lupus and also in clinical trials and research.
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And Victoria has led the way on how we assess lupus.
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She's built all the tools and has all the knowledge and insight.
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I think this is a great group of people to discuss a lot of the challenges.
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So I put the challenge out to the audience beginning three weeks ago with three weekly surveys.
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I'm sorry this is a busy slide. Top middle, survey number one answered by 312 rheumatologists from about 40 countries around the world.
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That was about lupus and cutaneous lupus.
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Survey number two, certain challenges — 151 responses with a one-time email survey.
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And then survey number three that went out just yesterday — this is about controversies in cutaneous lupus, 178 respondents.
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You can see the respondents were largely 85% rheumatologists.
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About 7 to 9% are APPs and there's about 3% other MDs, and that's probably dermatologists because we're trying to get dermatologists to sign on, but it could be internists as well.
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The other profile things are here. Bottom left you can see it's kind of split between males and females — really 58% male versus 42% female.
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We know in practice, in the real world, women are overtaking rheumatology.
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How many years have these folks been in practice?
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About half of them — this green up here and this blue over here — have really been in practice for about 20 to 40-plus years.
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They're kind of like me, the older gray-haired retiring tsunami of older male rheumatologists.
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And then where do they practice? You can see that a third of our responses have come from outside the United States, but within the United States the biggest areas are in the southeast and northeast where most of the fellowship training programs are, but there's really quite a good mix in here.
4:44
Lastly, upper top left, how many lupus patients do they see a week?
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On average, this green box here which is greater than 30 is a minority — that's only 13%.
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But you can see that the majority is this blue box 5 to 15 or this orange box meaning less than five.
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So somewhere between one and five patients are seen by about two-thirds of you rheumatologists who responded.
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So it's an important part of what you see.
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But again, that's 1 to 15 per month, which could be only four per week.
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I think lupus is still a big challenge. I think if you trained in certain centers — like I trained at Parkland, my god, everybody was born with lupus as far as I know in Dallas, Texas — I have tons of experience in lupus, but that's not the case for most of you as far as your training.
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And I think we rely on sessions like this and on research publications to get our experience that'll better prepare us for the patients we take care of.
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Panelists, want to make any comments about the profile of rheumatologists and what they're doing?
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Joe, you commented that the dermatologists are not represented well here.
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Yeah. No, look, I'll bring it up only because we have a spotlight on cutaneous lupus.
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I'll take the soapbox moment to say I'm very interested and excited to see the rheumatology responses.
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But I will say — and I won't speak for Vicki — I think we also hope that dermatologists will be stepping up to the plate to help diagnose and treat these patients as we get more emerging targeted therapies which are imminent and are coming.
6:35
So that I think was one of my takes on this because we really want to be collaborating for the best care of these patients.
6:46
I think this is fairly representative from the US perspective.
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And I like that this top right — how many years you've been in practice — the number that are less than 10 years, that's this orange box, 30%.
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These are young rheumatologists who are responding, so it's good to see what they think.
7:12
So let's get into it. I kind of moved the survey as it were meant to be interesting to you the audience.
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And I want to encourage the audience to put your comments in the Q&A box.
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If you have any comments or questions, let's get into this.
7:33
The first area for discussion is co-management.
7:37
Joe has been involved in a rheum-derm clinic from the time he was at Harvard and now he's at Southwestern.
7:44
He's got a fellowship for this. There are a number of programs around the country, but most of us didn't train in those.
7:52
I have my two medical dermatologists on speed dial on my phone and so I co-manage a lot.
8:00
But we asked this question: how often do you co-manage your cutaneous lupus patients in your practice?
8:12
More than 50% of the patients — that's 20-6% of you responding — but you can see it's pretty much all over the map.
8:20
"I don't need to" was less than 5%. Less than 10% was about 18%.
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So probably some very low number — less than 20% — are not very connected to dermatology, and that might be based on where they practice.
8:33
Jack, I just want to jump in. I wonder too — Vicki may want to comment — that some of this is driven by the phenotypic subset they're seeing, because cutaneous lupus is cutaneous lupus.
8:48
It may be people are seeing cutaneous lupus malar eruptions etc. and they say, you know, I got this and I'm treating it as part of SLE.
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But if they're more widespread or resistant discoid lupus, then they're managing differently.
9:03
Yeah. So it's hard to unpack what's behind this, but it would be interesting to kind of know that as well.
9:08
Yeah. And Maria brought up a really important point earlier.
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Throughout this session, I'm going to be talking about CLE — cutaneous lupus.
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That could be CLE exclusive like DLE by itself, and that might be seen by a dermatologist rather than a rheumatologist.
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But this is meant to be acute LE, chronic LE, subacute cutaneous LE — on top of or not on top of systemic manifestations — because these are decisions that we're all going to deal with.
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You know, does a CLE patient have systemic manifestations and what do I do about that?
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But if they don't, am I going to manage it? Is someone else going to manage it?
9:48
Another way of assessing co-management is how often do you require a skin biopsy?
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How do you confirm a diagnosis? Clinically — 21% said you do it clinically.
10:01
45% — skin biopsy from derm or skin biopsy that I do.
10:09
Biopsies are done 62% of the time overall.
10:11
I think it has to do with the subtype also, right?
10:17
Because if somebody has acute LE and they have nephritis and you know it's lupus and they have a malar rash, you're not going to do a biopsy.
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So it's really almost like different parts of the disease that people see, and that may be reflected in this as well.
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So before just one more second — top right says in patients who have suspected CLE how often do you get a skin biopsy?
10:47
A lot — 31% say half the time or more. I'm calling foul on this, but I think what the panelists are saying is it really is dependent upon what you're seeing and the scenario. Go ahead, Maria.
11:01
Oh yeah, no, I completely agree with what Vicki said.
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Joe, I think if the morphology is classic and it's in the right clinical context, then we often don't need the biopsy.
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But we often see patients that are falling kind of in between — we're worried about a mimicking condition.
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We'll talk about those later, but there are classic mimickers of cutaneous lupus that we don't want to miss.
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And I see this all the time where patients are referred for CLE and they've been escalated on an immunosuppressive, but in fact they have atopic derm, you know.
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So biopsies can be very helpful in certain situations with mimicking conditions.
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But the other thing is people often don't want to have a biopsy if it's in a cosmetically important place.
11:51
That's the other issue as well. So a lot of factors go into deciding if you're going to biopsy a patient.
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But at the end of the day, in my book, if there's any question about the diagnosis and it's going to change how you manage the patient, we really should get the biopsy.
12:06
And if I could just jump in, Jack — I would just say too, if you're sending one off, I'm always cautious to warn people: ideally it's going to a dermatopathologist.
12:15
Some rheumatologists send it off, it goes to gen path, and it comes back not always so helpful or kind of non-specific.
12:23
So do think about making sure it's reviewed by a dermatopathologist if that's the case.
12:27
Yeah. The other thing I would say is it's really important to do clinical-pathologic correlation because there are mimickers on the dermatopathology side as well.
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The changes that you see in lupus in the skin can also be seen in dermatomyositis.
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So it really does require going back to the patient to try to make the best diagnosis.
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So Maria gave us a good pearl in saying that when the skin manifestations are atypical and you think that treatment is going to change based on a biopsy result, that's a good indication.
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And b — consultation with a dermatopathologist.
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Anybody else want to offer up other pearls to the audience? Go ahead, Joe.
13:14
Yeah. I mean I think that one thing I will say is sometimes people will say, oh, in the past I have lupus, and they come in and they have something else going on, and it would be really nice to have a biopsy saying, yeah, this is consistent with lupus.
13:28
And then even if it may have been 10 years before, it puts a framework on things that you can't necessarily know when you're seeing them later.
13:37
Joe, do you have another one to add? Well, I'd agree.
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I think it's convincing — potentially referring colleagues and/or the patient — that indeed we're in the right or wrong bucket.
13:48
I had someone refer to me not long ago for, quote unquote, discoid lupus in the scalp.
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And it actually took the biopsy to really convince the referring physician to stop the lupus meds.
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It was indeed something called lichen planopilaris — a different entity.
14:05
And so just saying no, I assure you this is something else — I think it's helpful.
14:11
It's helpful for us to confirm our own diagnosis.
14:14
So a patient with a malar rash and no labs to support it — meaning they're ANA negative — or someone who, is that enough for you to send for a biopsy or just enough for you to get a consultation with dermatology?
14:34
Yeah. No, we see this all the time, right?
14:36
I think the tricky thing is, at least from my perspective being a non-dermatologist, erythematous lesions on the face are common.
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We see that just with flushing. We see that with rosacea, perioral dermatitis, seborrheic dermatitis — I mean the list goes on and on and on.
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And in those situations, patients — and I understand this — they don't want a biopsy in the central face.
15:03
But it's helpful for me to send to my dermatology colleague to also examine the patient.
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Is this rosacea? Is this not? What are some other clinical pearls in the history that might go for rosacea?
15:15
Worse with heat, worse with spicy food, not so much with light, which is more lupus.
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But to have another set of eyes who is an expert look at that patient can be very very helpful, because we see redness on the face all the time and we don't want to misdiagnose it as lupus if it's not lupus.
15:30
True. A little bit more on co-management here.
15:34
Who manages DLE patients in your practice?
15:38
You can see that rheumatologists are co-managing about 39% with dermatology, and then the rheumatologist doing it by themselves 22% — that's 60% where rheum is involved in DLE management.
15:51
But 39% are being managed by derm. I think this is highly appropriate. What do you guys think?
16:00
Well, you're preaching to the choir, but I think there's a lot of regional variation, right?
16:09
And if you're in the middle of a place where there's very little subspecialty expertise, it may be very difficult to know who should manage, and it's got to be who has the most experience.
16:19
I think in an academic center where people are focused on cutaneous lupus or autoimmune skin disease, it's maybe a bit of a different story
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because those people are really experts and are very comfortable not only evaluating the patient but also continuing to follow them to make sure they're
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not getting systemic findings — getting that regular urinalysis and blood counts.
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And I think that is something that we routinely do in our practice.
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You know, a comment is made: it's sometimes difficult to get a derm consult even in a busy city like Dallas.
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Do you — a) cultivate those relationships, b) do you think AI will fix this problem?
17:04
I mean, I have followed the literature on this.
17:08
There's very good literature about taking cell phone pictures and getting accurate diagnoses.
17:12
But ask a group of dermatologists about the use of AI to make diagnoses — they hate it, they are against it.
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Please comment about the future of AI and making skin diagnoses. Joe.
17:26
Well, I have to address the question about medical dermatology access in Dallas — I mean, how can I skip that?
17:32
We're happy to see your patients, feel free to reach out to me at some point.
17:36
Little tongue-in-cheek, right? But no, look, I want to comment too, just to build on what Vicki said.
17:43
I mean, the field of dermatology — I think rheumatology is heading this way a little bit — but a little subtlety under there is a lot of dermatology is moving toward PAs and NPs for first-line management and diagnosis.
18:03
And that's fine, but I do think there is an ongoing education need to really help people recognize and understand these lupus subtypes and phenotypes, which they may not be seeing all the time, and that puts them at higher risk maybe of missing it or not feeling comfortable treating it.
18:20
So I think it is going to be important to escalate education around these again as we get more therapies that will be relevant to the skin over time.
18:33
Yeah. I think AI can potentially — I mean the patients can take pictures right and they can find out a little quicker what's going on.
18:42
Some of these patients really wait a long time and they go to many different offices, not just rheum or derm.
18:48
And so I think it would be really helpful to really fast-forward to have a differential that would indicate where they should go to get treated.
18:57
And right now I think it's not so clear.
18:58
I mean, some of the mid-level providers — maybe even if it's lupus, they don't even know who's managing the patients.
19:05
So I actually think AI can facilitate getting patients to the right place.
19:09
You know, there's a JAAD article from this last year that published a really large cohort study showing that APPs in dermatology are providing the bulk of the care and are writing the bulk of the biologics in dermatology.
19:27
And so if you're a rheumatologist and you're not too keen on nurse practitioners or physician associates, you've got to change that because they're important and they're really good, by the way.
19:38
I mean, if you haven't dealt with them, I think that you should be looking forward to dealing with them going forward.
19:45
And yeah, I think having some of these folks on speed dial — I get consults all the time on the spot, just like they're going to send me someone.
19:54
Can you see this guy right now? Yeah, I'll do it.
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Because I know they're not going to send me nonsense and they know I'm going to have the right answer for someone who needs an answer right away.
20:08
Let's move on to the next slide and next set of questions.
20:11
This one I just wanted to get into SLE. I've got more on SLE I'll save till the end, but I wanted to put this up because I think how we assess systemic lupus bleeds over into how we assess cutaneous lupus.
20:26
So we asked the question: how do you judge SLE activity in your routine practice?
20:31
Majority answer was clinical judgment — 43%.
20:38
22% are using labs and serologies. That's about two-thirds of people getting clinical and labs to assess activity.
20:49
I'm surprised at the answer that says 29% of you use validated measures — SLEDAI, BILAG, LAI, DORIS.
21:00
I'm sorry. I don't think so. I'm with you on that one.
21:06
Here's what happens with survey questions, and it's partly my fault.
21:12
It's a bad question because all of us are doctors, which makes us kind of nerdy and wanting to always get the test question right.
21:19
So as opposed to how do you judge in your practice, they want to get the right answer, and so they might overstate their use of the SLEDAI.
21:28
I'd ask those folks that answered the SLEDAI: how many elements are there in the SLEDAI-2K and what is a mildly active versus severely active?
21:40
But the idea is I want each of you to talk about how lupus is assessed in practice and should we be using validated measures — if only to teach the audience how to better interpret clinical trial results.
21:56
Vicki, you invented the CLASI, and the same tool for dermatomyositis.
22:06
That's incredibly good and not easy to do in practice.
22:09
So you have an answer about this. Where do validated measures fit in practice?
22:14
Yeah. So what I will say is they fit very well into clinical trials where you're really trying to very fine-tunedly know what's happening with a new drug or a placebo group.
22:25
I think in clinical practice people are often doing more of a gestalt, and to some extent it's also impacted by how the patient feels about what they have.
22:37
So there's an interplay there that is harder to capture in a score.
22:41
But I think to do the CLASI — I mean, we do it on every single patient — but I'm rather surprised like you that so many people are doing an outcome measure.
22:53
So I would say a gestalt is fine. But when they say SLE disease activity, is that meaning CLE disease activity or just general?
23:03
I specifically asked about SLE activity on this one.
23:07
OK, we're going to ask about CLE measures next.
23:10
So what I will say there is I would be very uncomfortable not checking labs even on a stable patient who's had not much activity in their skin — I'm going to be checking a urinalysis at least every year and more often if there are other features of concern about the patient.
23:25
So I think that's part and parcel of following these patients — really important.
23:34
And I'll give the rheumatologists a little credit: some of you may not do those routinely, but some of you are connected to colleagues that
23:46
do clinical trials, and if they do clinical trials you may have a checklist in front of you — for someone to get into this
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study they need to have, you know, the SLEDAI-2K checklist — and maybe other measures. So you become indirectly familiar.
24:04
Joe, what do you teach the residents and/or fellows that rotate through your combined clinic?
24:10
Yeah. I mean, I'll say two things. Yeah, I'll build on Vicki's comment.
24:15
I think it's a little bit older data, but from the Toronto cohort I always like to teach and remind them that something like 20% of patients who were seemingly asymptomatic had a clinically actionable lab finding.
24:34
So we're also, like Vicki, very aggressive about routine lab monitoring for activity markers over time.
24:44
Being an academic center, we do measure some activity, but Vicki knows my answer to this — she also helped develop with me an IGA instrument which is sort of gestalt-based, but we have a simple IGA of clear, almost clear, mild, moderate, severe when it comes to skin lupus.
25:01
We could talk about that with CLE measures, but those to me at least — everyone can interpret clear, almost clear, whether it's from a trial or in clinic — and I find those a little bit easier.
25:14
But let's be honest, I don't think most are doing extensive validated measures in everyday routine clinical practice. It's just not being done routinely.
25:32
Right. So I then turned the tables. I asked later on a question about cutaneous lupus.
25:43
And I asked the audience: in patients who have DLE — discoid lupus — or subacute cutaneous lupus — which, by the way, was identified and founded at UT Southwestern by Jim Gilliam and Rick Sontheimer with the SSA association — what labs do you routinely order?
26:07
I was kind of baiting them saying, do you really need labs in chronic skin lupus?
26:11
And you can see that a lot of this is appropriate.
26:16
SSA was the dominant answer — that makes some sense.
26:21
ANAs seem to make sense. Sed rates — I probably should have put in a UA, like you said.
26:26
But 34% are doing double-stranded DNA and/or complements.
26:31
Is that overkill or not? What do you think, Maria?
26:34
Well, I mean I think this is a great question.
26:38
When in rheumatology we see patients with DLE and/or SLE, it's always in association with SLE, right — in the rheumatology office.
26:48
So therefore we are monitoring with kind of the plethora of autoantibodies that we're doing for routine monitoring for other organ system manifestations of lupus.
27:01
Is lupus nephritis percolating up? What some might argue is that every-3-month anti-dsDNA, every-3-month complement is overkill.
27:11
We do that again because we're assessing the immunologic activity of the disease as a whole, not just the skin.
27:19
Now, I think I'd love to hear from Joe and Vicki — in patients with primary discoid or not with SLE, maybe it's different, right?
27:29
I mean I'll just again remind — I think taking the rheumatology hat off and putting the derm hat on for a moment — you all know, local in particular, localized discoid lupus patients — there's a large number of these patients who are even ANA negative, who have no serologic positivity.
27:47
There are some cross-sectional estimates that vary depending on whether it's more generalized lesions or more localized.
27:59
So a patient with a few localized lesions who's ANA negative — am I doing extensive routine serologies on everyone?
28:11
No, and not with great frequency. I think we have to put it in clinical context.
28:17
We're asking history and review of systems of all these patients, of course.
28:20
We're doing screening labs, of course. But not all these patients have active serologies and a lot of active systemic disease necessarily.
28:34
I like your comment about framing it as who's seeing the patient.
28:38
And as we came full circle to the beginning — is this DLE with SLE, or is it DLE alone?
28:46
So I do think we can contextualize it to some degree.
28:49
The SLE patients — you can keep me honest — 75% plus, probably more, are SSA-positive, so it's helpful to corroborate that diagnosis.
29:04
So there are scenarios, but do we routinely check it all the time?
29:11
I've had patients — and I'll let Vicki comment — who have had burnt-out discoid lupus for 10 years in their scalp.
29:18
Am I still going to be checking double-stranded DNA every three months?
29:21
I think that's probably not a good use of resources.
29:25
But I might be checking a urinalysis once a year, because that is really the one thing — if you think about all the tests that we measure — it's like, well, what is the risk they're going to get renal disease?
29:38
And if there's no proteinuria, I tend to worry a lot less. So yeah.
29:43
So I asked the audience: in your practice, the most problematic form of CLE is what?
29:53
And their number one answer was — it was kind of a mix — but it was mainly DLE at 37%, followed by the other
30:02
usually hard-to-spell forms of CLE: lupus tumidus, profundus, panniculitis, and whatnot — because we usually when we get that back on a biopsy or from
30:11
a derm report we're like, what the heck, and what am I doing about this?
30:14
And then those are the dominant things. I was surprised that acute LE malar rash, mucosal lupus, and alopecia with lupus are relatively minor concerns of the majority of the audience.
30:32
I think you know, this is one of those 300-plus respondents. Does that surprise any of you?
30:38
I don't think so, because I think it reflects the fact that — we're thinking in terms of — even though we're saying CLE — the types of alopecia that are frequently seen in SLE patients are more of a diffuse non-scarring type of alopecia and it responds to steroids when you're treating their disease.
30:57
And I think the same thing with acute LE — it tends to be fairly responsive to many treatments.
31:02
So in terms of management I do think the emphasis is more on the subtypes of discoid and others that are probably a little more problematic in terms of initial treatment.
31:14
Totally agree. Yeah.
31:17
So with chronic skin LE, hydroxychloroquine is a big part.
31:25
And then the next several questions are about what do you do after hydroxychloroquine.
31:29
I wanted to start by asking our panelists what's their feeling about the status of hydroxychloroquine blood levels, which have become more and more popular but yet are not always available.
31:45
You can see that the audience says half the time they're not available.
31:50
A quarter of the time they're selective about their use, or they're rarely using it.
31:56
And only 8% are routinely using hydroxychloroquine levels — and I'm going to assume that's in anybody on hydroxychloroquine with SLE or even with CLE.
32:06
Each of you, how often are you doing hydroxychloroquine levels and where do they fit in CLE management? Joe?
32:14
Yeah, I do not use them frequently. I'm happy to hear from others.
32:20
I'd say the two scenarios where I've maybe found it a little bit helpful — I've checked it on rare occasion.
32:25
One is the patient who's truly had no response to antimalarials.
32:30
We have limited options, and you know there's a shocking truth here, which is there's been a study in skin lupus that something like 20% of patients when you check hydroxychloroquine blood levels in CLE for those who are not responding aren't taking it — it's a zero level.
32:46
Right. So it's truth serum testing as opposed to hydroxychloroquine serum blood testing.
32:54
But that's one scenario. The only other one I will say is when the AAO moved the recommendations from 6.5 mg/kg down to 5 mg/kg, I do think there are some patients who may benefit from slightly higher doses relative to their body weight.
33:14
I'll negotiate sometimes if they have a little residual disease — I've used this to try to push therapeutic range, to convince the ophthalmologist or others that we can dose it a little bit higher.
33:26
But all that said, all that hot air, I rarely use it to be completely honest with you.
33:30
Maria, what about you?
33:32
Yeah, it's interesting. So I've become a complete adopter of these blood levels and I was a late adopter.
33:41
I would say it's been about 10 months that I'm now sending them on everybody.
33:46
I have the luxury of being able to get them — we have it at the university, but also at our local commercial labs as well.
33:55
Very easy to get. Never had trouble with any kind of reimbursement.
34:00
And it has been humbling, because yes, you have some of those patients where the level comes back at less than 200 — they're just not taking the medication — and then you can have a very nice conversation about some of those challenges.
34:12
But I find it also very interesting in those patients that are taking it as prescribed by the weight-based dosing that I prescribed, but for whatever reason — absorption, metabolism — they're just low.
34:30
Their levels are 500, 600. And so I am then trying to do what I can to titrate that dose.
34:37
I recheck another level to try to get between that 750 to 1150 range.
34:42
I know we don't have perfect data to say that if I increase to that range I'm going to improve, but we know what the range is where the best efficacy is and the least toxicity in terms of the retina.
34:55
So it's very interesting. I've switched my practice completely in doing this now, but I think it's because I have it available to me. That's why, right?
35:03
So — I don't mean to cut off — so it's interesting.
35:10
One thing I'll say — a little bit like therapeutic drug monitoring in IBD versus what we do in psoriasis — I think it's because I have the skin to give me an answer immediately in front of me as opposed to some more subjective endpoint.
35:27
That might drive a little bit of my decisions around serologic levels.
35:30
But the other question I have is: do you feel comfortable going supra-therapeutic — meaning would that actually push you beyond the range, up to 400 milligrams daily?
35:40
Would you have a level at which you would say, oh, I'll give you 600 milligrams daily?
35:44
Do you push it beyond — Michelle Petri does 400?
35:46
No. And that's my question, because I think I would probably move on to something else at that point. It would make me anxious.
35:52
Yeah. I haven't pushed it like Michelle does.
35:56
But I think maybe I'm just scared. Yeah.
36:00
Well, and the other thing is that the timing of when the blood is drawn is somewhat important as well.
36:06
And I think that's another variable that has to be thought about at least.
36:10
It's supposed to be at least 6 to 8 hours after the last dose.
36:12
And is that what we're really actually doing?
36:15
So that's another thing that's hard to understand completely.
36:19
You know, a commenter says he does it all the time using just a fingerprick.
36:25
I think the bottom line is most of us assume it's not available to us, but I think we haven't really pushed hard on it.
36:33
And I'll support Joe in saying it's not routinely available on the UT Southwestern campus, but it's not like they haven't been asked.
36:48
Anyhow, okay, let's get into hydroxychloroquine.
36:49
If a cutaneous lupus patient — again, cutaneous lupus, DLE, scalp, one of those hard-to-pronounce CLEs — is not controlled by hydroxychloroquine, my next preferred
37:00
therapy is — and the number one answer was 40% methotrexate, 16% a biologic, 15% are sticking with topicals — but then there's a mix
37:10
of mycophenolate, quinacrine at 7%, azathioprine, calcineurin inhibitors.
37:19
There's quite a spread after methotrexate.
37:23
So I think you guys have the expertise. Do you want to give me your answer to this question? Let's start with Vicki.
37:32
Well, there's not — I'm going to say there's not a right answer.
37:37
And part of it is if somebody has really severe disease and you don't want to sit around for two or three months to see
37:44
if hydroxychloroquine is going to work — and they're losing hair and scarring — you're going to probably change the order of things a little
37:53
bit and maybe go to methotrexate or mycophenolate a little sooner and put somebody on hydroxychloroquine and maybe think about backing down later on the
38:01
methotrexate.
38:01
However, for a lot of patients — definitely hydroxychloroquine — and then I'm a little biased — not all my patients want to stop drinking alcohol or have to get their bloods drawn all the time.
38:13
And so I do use quinacrine quite frequently.
38:16
And I do find it beneficial and it's sort of an intermediary step before going to immunosuppression.
38:22
So that's something that I personally do.
38:24
I think most people do not. And then I use a lot of mycophenolate when methotrexate doesn't work.
38:30
We use topicals but none of them are hugely effective in general, and they're more adjunctive therapies except if somebody has really mild disease or maybe very mild disease on the face.
38:41
Azathioprine — I don't think works quite as well for skin as methotrexate or mycophenolate.
38:47
And I don't use a lot of calcineurin inhibitors — I worry too much about some of the side effects with chronic use.
38:54
And it does need to be used more chronically probably if you're going to go that way.
38:58
By when you start quinacrine, do you stop the hydroxychloroquine?
39:02
No, I use them together. I think there's some synergistic interaction.
39:07
They actually work on different cell types.
39:12
It turns out that quinacrine has effects on TLR8 which hydroxychloroquine does not, and that's present on some of the macrophages in the skin and myeloid dendritic cells.
39:21
So they really work differently and you can actually see differences when you do biopsies between these people.
39:26
So I do think I like to use it synergistically. Do you have to? We don't know that.
39:34
Anybody else have any preferences? Maria, how is this handled from a guideline standpoint?
39:40
Yeah, so we had — as Vicki knows — we had a lot of discussion and debate about this question.
39:47
And I can just boil it down by saying that the voting panel's preferences based upon their personal experience — not based upon high-level evidence in the literature, but based upon their personal experience — was to start with methotrexate, right Vicki?
40:05
That's what we kind of came down with when you look at the list.
40:10
But also mycophenolate showed a lot of benefit and experience as well.
40:15
Agree that azathioprine and the calcineurin inhibitors were much lower down, didn't have the same experience.
40:20
But I think what's interesting — and I'd love to hear again from my friends and colleagues here — at least from the rheumatology perspective, I think what's happening now in the clinic is a lot depends on, first of all, holistically what else is active in the lupus, right?
40:38
Because you want to choose a medication that is going to be able to treat all the manifestations.
40:43
Now, let's just say we're focused purely on the skin as being the active manifestation.
40:49
Then what is that phenotype? If you have a scarring phenotype like DLE, honestly, we might go right to a type 1 interferon antagonist.
40:57
Yes, right. Because it's going to act quickly, it's going to stop the inflammatory process.
41:02
I worry personally — even though the guideline says methotrexate first — I worry about ramping up methotrexate or even mycophenolate in scarring lesions when we have a therapy that can work amazingly quickly and effectively to shut down that inflammation.
41:23
And the other thing — in the old days before we had these newer therapies — for these patients with scarring lesions, we often had to use a lot of glucocorticoids, right?
41:35
And we want to avoid glucocorticoids, and we have been able to avoid glucocorticoids often by the early introduction of the type 1 interferon antagonist.
41:47
So Maria, what I will say about anifrolumab — which I totally agree with, it really works very quickly — and I think some of the newer treatments coming along are going to work equally quickly.
42:00
But they're not approved right now for CLE, and so getting a label is not so easy.
42:05
That will change in the near future but right now that's not the case.
42:11
And I think that in the guidelines, methotrexate, mycophenolate, and the biologics were given equal weighting, and part of that is because we don't have comparative studies — and that's sort of the basis for being able to give a hierarchy.
42:22
But I agree with you that if someone's really rapidly scarring, you're going to want to do something that works quickly. Yeah.
42:28
You know, Joe, there are a number of therapies that are going after a CLE indication and that's going to be happening, you know, end of this year and into 2027.
42:40
Can you give the audience a preview of what drugs to be looking forward to as potential drugs to use in skin lupus?
42:50
Yeah, I'm happy to. And I would just say I agree with everything that's been said and hopefully some of these I'm going to mention
42:57
will move a little bit further up in our algorithm, because we do want to avoid the scarring, we do want to get these patients
43:06
under good control, as Maria and Vicki mentioned.
43:10
Yeah, a couple things coming. Obviously Vicki mentioned anifrolumab in trials for CLE, so hopefully we'll have more insight there.
43:19
There is a drug called litifilimab — it's a BDCA2 inhibitor, essentially works on plasmacytoid dendritic cells to decrease type 1 interferon and some other relevant cytokines.
43:29
We've seen good data — Vicki and I have been somewhat involved in that program over time — now 52-week data that was just shown in fact at EADV, very very promising for skin lupus.
43:42
I'll tell you off-label, and there's a phase 2 of deucravacitinib, a TYK2 inhibitor, which to my understanding unfortunately is not really moving forward with CLE by itself.
43:51
But the phase 2 — there's a Lancet Rheumatology article, stay tuned — was very helpful.
44:01
I've used it off-label. We've published on it off-label for a number of skin lupus patients.
44:04
It's been very helpful. And then there's the TLR7/8 inhibitor — there's imsidolimab and afimetoran, if I have the names right — those are also
44:18
looking good and have made strides in doing what Vicki's been asking for for years, which are CLE-dedicated or CLE-enriched studies using the CLASI and
44:29
really looking for regulatory approval and using the proper endpoints.
44:33
So I think there's a lot coming. And Vicki, tell me if I left anything out, but I think those are some of the highlight drugs coming.
44:39
Well, the only other one is daxdilimab, which is an antibody that depletes the PDCs and they have really interesting phase 2 data and are going into phase 3.
44:51
So I mean the number of targets now is amazing, and what's really similar among them is the impact on type 1 interferon.
44:59
Yes, and imsidolimab similarly has shown skin data as well, so sorry for leaving that out. Yeah.
45:07
So I want to — instead of getting to the other thing about bullous LE that everybody can look at on their own — where the right answer, by the way, is dapsone is a first choice — there is this trend now.
45:20
We had all these agents being developed in CLE for an indication of use in lupus.
45:27
I think that's brilliant because we've had two to three decades of difficulty getting drugs approved in lupus that we know they work there, we're
45:38
sure they work, but lupus is really difficult to corral and to prove, and has high placebo response rates, and not every drug's going to
45:45
work, and we have probably more failures than successes.
45:47
But yes, our arsenal of lupus therapies has grown with lupus indications and now nephritis indications.
45:58
Going after a CLE indication is brilliant, especially with Vicki's CLASI as a primary endpoint that the FDA accepts.
46:06
Can each of you talk about the pathway to drug approval in lupus by first going through skin?
46:14
Yeah. Well, I guess that's what's happening now with the TLR7/8 inhibitor, right?
46:18
They did an SLE trial, a CLE trial. It worked really well.
46:23
This is afimetoran. It worked really well in CLE, and so they decided to go for a phase 3 with CLE with or without SLE
46:35
— which is actually I think a first — and I think it makes a whole lot of sense, and obviously not screening out really
46:43
severe SLE, but I think it makes sense looking at where it's working in the phase 2 and then going in that direction.
46:51
Okay. Any other comment on that pathway? I've got — I'm going to move on.
46:55
To problematic CLE and difficult-to-treat lupus skin disease — my preferred treatment is: upper left, anifrolumab 58%, a B-cell inhibitor approach — belimumab or rituximab — in 13%.
47:14
We're now at 70%. That's what difficult CLE without having an indication drug — those are being developed.
47:22
There are even a few people that would use thalidomide, or we talked about quinacrine earlier.
47:28
Is this pretty much what you guys are doing right now?
47:31
Because Maria, you talked about anifrolumab having a surprisingly effective and rapid response.
47:40
I mean, Jack, I'm happy to — I'd call these folks sort of the third line, right?
47:44
Because we talked about second line already after antimalarials.
47:50
The historic intervention for us — being very skin-focused and thinking maybe about the discoid lupus patient that was hard to treat — was thalidomide/lenalidomide.
48:00
And Vicki had very nice data on that in the past as well, showing that it captured a lot of these patients who had been through second-line therapy.
48:08
I would say in the current era — and I'll make one other comment — I have been wholly underwhelmed by the B-cell inhibitors for most of our cutaneous lupus phenotypes, to be completely honest.
48:22
We have limited skin-specific data and in our hands it's not terribly helpful.
48:28
So I would say historically it was lenalidomide; current era, absolutely I'd be reaching for anifrolumab, and hoping to reach for litifilimab and others.
48:37
Absolutely. And I think that very much supplants any kind of third-line use I would have considered for those in the past.
48:43
I do want to bring up one thing about bullous lupus, which is — I agree that dapsone is first-line especially for more mild to
48:53
moderate disease — but for the really severe patients it's important to know that rituximab, because it is a B-cell-driven disease, can really make a
49:00
difference and put the disease into temporary remission.
49:04
Well, that's really good to know. Oh, it's interesting because I struggle with — first of all, I agree with everything that's been said — the role now of the newer anti-CD20, obinutuzumab, and what is that role going to be with cutaneous lupus.
49:21
And I do wonder if it's going to come down to the phenotype — is it acute cutaneous?
49:27
Maybe it's going to be really good for acute cutaneous versus DLE.
49:31
I know that there'll be an abstract — I think Advital is the first author — presented next week at the ACR looking at an
49:41
analysis of the ALLEGORY trial, which is the phase 3 obinutuzumab extrarenal trial, and looking at Vicki's CLASI — the CLASI endpoint — so looking
49:50
at a skin-specific endpoint in that trial.
49:54
And via the abstract that's been published, the results look very promising.
49:58
And again the question in my mind that I want to delve into — what is the phenotype of the cutaneous lupus that improved?
50:07
Because we are all aware of the older data that Evelyne published looking at worsening of DLE in SLE with rituximab — the first-generation anti-CD20 — worsening of those lesions.
50:20
And Vicki, I remember when this first came out, I remember calling you and I said, can you explain to me what is going on in these lesions?
50:27
Because these lesions when you look on biopsy are full of B cells — but perhaps these are regulatory B cells, right?
50:33
These are non-pathogenic B cells. But it's always been this interesting thing — this paradoxical response to the anti-CD20s with the DLE subtype.
50:43
So I think stay tuned for that — we have to think about that some more.
50:46
Yeah. Yeah, I mean it turns out there are B cells in discoid lupus, not so many in the other subtypes.
50:58
And maybe what's happening is that there are B-regulatory cells that are also depleted early on, and that may be part of why they flare.
51:04
And maybe over time there's some slight response.
51:06
Ed's early paper was this flaring and then over time it seemed things settled down a bit, and so it could be that the B-regs being knocked out were a problem.
51:15
And I don't know that that's ever been formally shown as the hypothesis.
51:18
And Maria, I'm presuming they again — as they did — did not pick apart phenotypic subset, because it may very well be the case that the ACLE and such in that SLE population improves, but would it improve or have no impact on DLE in SLE? I don't know if we know. So yeah.
51:39
Right. Well, I like that you brought up the subsetting and phenotyping, because I asked this question about when do you primarily use anifrolumab in
51:47
lupus — not talking about SLE or CLE, because as you know when those trials came out there were sort of mixed results, and the
51:56
subanalysis showed that it worked really well for skin and really well for joint.
52:00
And so I asked the audience — because the buzz is anifrolumab — and this is kind of what I think may happen in the future as we get more CLE-approved drugs: how are they going to be used?
52:11
So where do you primarily use it? And the audience — more than half the time — chose problematic cutaneous lupus.
52:19
In arthritis-predominant lupus it was very little, only about 9%.
52:24
26% are not using anifrolumab at all. Very few are using it for lupus nephritis.
52:31
And some are using it for refractory severe lupus.
52:35
So I think that seems somewhat predictive of where maybe new CLE-indication drugs may go. Any comment?
52:46
Yeah. No, I totally agree. I think all the early trials look like many of them work well in many patients, and not surprisingly, because the interferon comes down very quickly.
52:58
So what it may well be is that there may be subtle differences in the side effect profiles that we see, and that's going to end up being a really important aspect of what needs to be looked at in the near-term future as these new drugs roll out.
53:10
And Jack, if I could add — I think Vicki and I have shared this too, and please don't fax me any safety reports, you heard it here first — but I'll also say we've talked about this, that we've had patients who have done brilliantly on skin disease.
53:25
I had one fairly recently where they were transitioned from mycophenolate onto anifrolumab — skin looked beautiful — but boy did they have a rip-roaring nephritis kick off shortly after.
53:41
And so I'm a little bit cautious and I just like to monitor and watch around those transitions as we learn more about these.
53:48
And I think we both also have shared some concern about what it would look like when you pull these drugs away and just watching for flares.
53:54
We don't have a lot of withdrawal data right now.
53:57
And how will things, or might things, flare?
54:00
I don't know. But it's also interesting to think that litifilimab or some of these other mechanisms might have a little bit different cadence, and PD, and what that looks like in terms of impacting not just type 1 interferon but other cytokines, and also what withdrawal might look like.
54:20
So I think we need to learn a lot yet about how these behave.
54:24
I love that point. Oh, sorry, Jack. Go ahead.
54:26
I was just going to say I love that point.
54:28
And I think all of us that take care of lupus patients in this group — the reality is we can't expect one targeted therapy to be able to treat all manifestations, because likely there are different biological pathways operative in various manifestations at various phases of the disease.
54:50
It's so complicated, and we know the molecular heterogeneity.
54:54
So for example, my patient yesterday — her skin beautifully controlled only on anifrolumab, beautifully controlled — however, lupus inflammatory arthritis exploded on the anifrolumab.
55:13
So guess what? I have her on anifrolumab and obinutuzumab and she's doing beautifully.
55:21
But I guess what I'm trying to say is that sometimes, when we take care of the patient in front of us, we have to do things in a way that is biologically rational and in a way that is safe.
55:37
We're very closely monitoring. Some of these patients need their lives back — we have to help them.
55:42
And so I think this is where the future is.
55:45
And so Joe, I love what you just said, that perhaps some of these new therapies coming through — maybe they're going to hit more arms of the immune system — and perhaps we'll have efficacy more across domains. So it's very interesting.
55:59
Well, the hour has gone very fast. I want to thank our panel for an excellent hour of insight, advice, and answering some new questions that we are dealing with and that we're going to deal with in the near future.
56:17
I think this has been really valuable for the audience.
56:18
Tell your peers they can see this on RheumNow.
56:24
It'll also be appearing on LinkedIn and on Twitter, and you can hear the podcast going forward.
56:31
It'll be available for everyone to hear.
56:34
Joe, Maria, Victoria — thanks so much for a great hour. Thank you. Bye bye.
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