Cutaneous Lupus Erythematosus: Pipeline Updates, Systemic Risk, and Shared Decision-Making

Dr Joseph Merola highlights major advances in the cutaneous lupus erythematosus (CLE) pipeline, including targeted therapies such as litifilimab, anifrolumab, TYK2 inhibitors, and TLR7/8 antagonists. Learn how dermatologists can approach screening for systemic lupus, collaborate with rheumatology, and implement shared decision-making to balance efficacy, safety, and whole-patient care.

Transcript

Hi, I'm Dr Joseph Merola. I'm a dermatologist and rheumatologist and professor and chair of dermatology at UT Southwestern Medical Center in Dallas, Texas, where I'm also in the Department of Rheumatology and the Public Health School.

What recent updates in the CLE therapeutic pipeline are most likely to impact dermatology practice in the near term?

Dr Merola: Yes, there's some really, really exciting new developments for, in particular, cutaneous lupus as well as systemic lupus. Being focused a little bit for the moment on cutaneous lupus, we really have not had an FDA-approved drug for that specific condition to date. And as many folks know, we have cycled through a number of older medications that have some challenged tolerability, safety monitoring concerns, particularly concerns in pregnancy or in women of childbearing potential with regard to risk of pregnancy and teratogenicity. Drugs like methotrexate, mycophenolate, thalidomide, and lenalidomide. What's really exciting in the current era is that we have a whole pipeline of drugs that are targeted, have shown to date very, very reassuring safety profiles and very promising efficacy. 

Some of the drugs that we covered here at the masterclasses in dermatology meeting 2026 include novel molecules such as litifilimab. Litifilimab is a BDC, plasmacytoid dendritic cell inhibitor, which works by binding to the BDCA2 molecule on that particular cell. Ultimately inhibits type 1 interferon production as well as a number of other inflammatory cytokines. And what's very exciting is that there's phase 2 data showing impressive efficacy in cutaneous lupus and we're waiting with beta breath for phase three data as well from this program, as well as data in SLE from this program. And so that's, I think, one of the things I'm most excited about presently. 

We also have anifrolumab, which is approved for systemic lupus currently as an IV formulation that is being looked at for cutaneous lupus as well. Many of us have had experience using that drug for cutaneous lupus with very exceptional results in many cases. And so we're waiting as well for the data from that program, as well as data that might suggest its opportunity as a subcutaneous formulation. Third, we talked about TYK2 inhibition, in particular some data from deucravacitinib, looking at cutaneous lupus and systemic lupus, which again looks very, very promising. We've seen some data from a phase 2 program dedicated to CLE. And again, I think many of us have talked about publications that we've had of patients who have had positive experience using that particular mechanism. 

And finally, we covered a drug called Enpatoran, which is a TLR78 antagonist. It is also been looked at in cutaneous lupus. And in particular, we've seen some data from a phase 2 cutaneous lupus program, which looks very, very promising as well, and is moving on to a phase 3 program. 

And so I'm probably missing something except to say that it's a very exciting time for us in cutaneous lupus to be seeing what the pipeline holds and to have targeted therapeutics that really will help us as dermatologists treat our patients and to collaborate with rheumatologists around the best treatment for skin and systemic lupus patients.

How should dermatologists approach the intersection of cutaneous lupus and systemic lupus when it comes to screening, referral, and shared management?

Dr Merola: Yeah. So when we think about the dermatologist's role in cutaneous lupus management, I think I'd like to start first by reminding folks that a majority of our patients, up to 75% of our cutaneous lupus patients may not have a diagnosis of systemic lupus. And so on many fronts, we as dermatologists need to be treating these patients. There are patients. We're seeing particularly the patients who have phenotypic subsets such as subacute cutaneous lupus and discoid lupus among the many variants of disease, which are squarely in our wheelhouse. As dermatologists, we have to treat their skin. 

And in terms of screening and monitoring, we've talked a little bit about here at Masterclasses in Dermatology 2026, some approaches to screening that are low burden on the dermatologist, as well as when to think about co-management. And at very high level, for the dermatologists seeing a cutaneous lupus patient, say a patient with discoid lupus, it's very reasonable to start with basic screening, history, review of systems. Does the patient have any other symptoms that might make you concerned? Active arthritis, mouth ulcers, fevers, chills, et cetera, et cetera. In a patient that feels otherwise systemically well, very reassuring, we then move on to considering some laboratory testing. And again, this doesn't have to be high burden on the dermatologist, but certainly some basic lab tests that include what you might expect, perhaps CBC, CMP, but thinking about a screening ANA as well as a urinalysis and an advanced screening or disease state activity monitoring based on what one finds. 

And it is always okay to call a friend, phone a friend, and collaborate with your local friendly rheumatologist if there's suspicion that the patient has systemic features of disease and/or systemic lupus. We shared a nice publication that we recently had in the JCAD that goes through a nice algorithm for how to screen and monitor for systemic lupus in the cutaneous lupus patient for the dermatologist, which you might find helpful. And I think really, again, just to summarize that as dermatologists, we have to treat the skin and then we can decide where we feel comfortable with management of any systemic manifestations.

What practical strategies can clinicians use to incorporate shared decision-making into long-term lupus care while balancing efficacy and safety?

Dr Merola: Yeah. When we think about the shared management of skin and systemic lupus, to begin with, we, again, as dermatologists need to be owning the skin component of disease. We're the providers who best know how to care for the skin, make sure that the differential diagnosis has been thought through, that indeed the patient has cutaneous lupus and not a mimicker disease. Once we've arrived at that diagnosis, again, we are currently and increasingly in the future going to have access to a number of targeted therapeutics facing the dermatologist to really treat these patients, treat them to hopefully very, very acceptable disease activity levels, if not low disease activity or clear, which is the hope eventually. All that said, we certainly can and should partner with a rheumatologist around other manifestations or potential systemic manifestations of lupus. And to give a very obvious example, we have to align the skin disease manifestation treatment with what might be happening in other end organ systems.

And one of the things we covered at the masterclasses in dermatology 2026 meeting was talking about, by domain of disease, how we might best pair or partner with the rheumatologist on treatment. For example, for patients maybe who are on background hydroxychloroquine, which is probably a good backbone therapy for most of our patients with skin and systemic lupus, if they have arthritis and we're trying to pick another second line agent, might we consider a methotrexate where we're happy, we can happily collaborate with the rheumatologist on a drug that would help skin and joint disease. If it's a patient with nephritis, making sure that we're aligning drugs that we know to treat the nephritis component of disease with the skin, we may align on mycophenolate therapy or perhaps one of the newer targeted systemic biologics, for example. So without going into every example, we reviewed which drugs line up with both skin as well as other manifestations, how we can collaborate with our rheumatology colleagues to get patients to the best place. And again, just beginning to understand how newer therapies will help us treat not just skin, but sort of the whole lupus patient.