Expanding the HS Treatment Landscape: From Single-Pathway Therapy to Personalized Care

The treatment landscape for hidradenitis suppurativa (HS) is undergoing rapid transformation, with more than 24 biologics and small molecule inhibitors in development targeting a wide range of inflammatory pathways. In this interview, Leandra A. Barnes, MD, FAAD, discusses how this growing pipeline reflects a shift away from one-size-fits-all therapy toward more personalized, phenotype-driven care. Dr Barnes also addresses persistent gaps in patient education and treatment satisfaction, the evolving role of higher efficacy endpoints, and practical strategies for navigating access barriers in clinical practice.
 

The Dermatologist: How should clinicians interpret the rapidly expanding pipeline for HS, and what does it signal about future treatment paradigms?
Dr Barnes: There is a huge volume of agents, both in development currently and those recently developed or under investigation. And these agents highlight something we have known for a long time, which is that HS is not a single-pathway disease. We currently have 24 to 26 therapies under active investigation right now, spanning many different pathways: TNF alpha inhibitors, IL-17 inhibitors, IL-1 inhibitors, JAK inhibitors, BTK inhibitors, IRAK4 degraders, and beyond. This signals a shift away from the one-size-fits-all model that we have had to live with for many years. Practically, it says that we are moving toward a future in which treatment selection can be much more nuanced and where we will be able to consider the patient’s disease phenotype, comorbidities, preferences for an oral or injectable medication, and especially their prior treatment history. It is also a signal to clinicians to stay engaged with patients who may not be responding adequately today because there are more options coming, and they are coming fast. It is going well beyond repurposed inflammatory agents for other diseases; we have novel biologics and novel small molecule inhibitors. This is an exciting time.

The Dermatologist: Despite multiple FDA-approved biologics, about half of patients remain dissatisfied with treatment. What are the key gaps that these emerging therapies aim to address?
Dr Barnes: This dissatisfaction is one of the most important problems that we are facing right now. And even more striking, 56% of patients report that their physicians never even told them about the FDA-approved treatment options for HS. So, this gap is not just biologic or mechanistic; it is, unfortunately, also a physician knowledge gap. I have been fortunate to work with one of the key leaders in the HS space, my mentor Dr Haley Nayak, to uncover some of these barriers that patients are facing with qualitative interviews. 

On the clinical side, one of the real limitations to our current options is that we are using HiSCR50. This means that we are looking for at least a 50% reduction in total abscesses and inflammatory nodule count from baseline and no increase in abscess and draining tunnel count. Even though that is a meaningful bar, it still leaves a lot of disease burden behind. Imagine being patted on the back for only being 50% better. And even with 50% improvement, many people are still experiencing significant pain, draining tunnels, scarring, and new lesions. These emerging therapies, and some exciting trials happening right now, are increasingly using higher benchmarks, such as HiSCR75 and HiSCR90, as endpoints.

The Dermatologist: How do you approach the decision between biologic therapies and small molecule inhibitors in HS, considering differences in administration, mechanism, and patient preference?
Dr Barnes: We always want to make sure that we are using a patient-centered approach because everyone is different and there is no universal right answer. At the most basic level, biologics are large, protein-based molecules typically given by injection or infusion, and they typically require refrigeration and administration by a nurse or in an infusion center. Whereas small molecule inhibitors, such as the JAK1 inhibitors currently in phase 3 trials, are orally administered. They are chemically synthesized, much more shelf stable, and the molecules are a lot smaller than biologics. You can imagine there are patients who would prefer to get an injection every week or every so often vs those who would rather not have to deal with needles and are willing to consistently take the medication by mouth every day. Even just this week, a patient who was considering switching to the oral medication realized that it would be hard for her to remember to take a pill at around the same time every day, so we are going to stick with the injections. 

We also need to consider side effects or potential contraindications. For example, if someone has a history of thromboembolic events, we cannot give them a small molecule inhibitor. In addition, there are newer trials with different mechanisms that could theoretically allow for deeper tissue penetration; for example, sonelokimab, a trivalent nanobody that inhibits both IL-17A and IL-17F. Impressive deep clinical responses were presented at the 2026 American Academy of Dermatology Annual Meeting latebreaking sessions. Ultimately, the approach is to meet patients where they are, explain the options clearly, and factor in their disease severity, comorbidities, and preferences.

The Dermatologist: Clinical trials are increasingly using higher thresholds, such as HiSCR75 and HiSCR90. How might these more stringent endpoints change expectations for treatment success in clinical practice?
Dr Barnes: I think this is one of the most important evolutions happening in HS right now. HiSCR50 was the endpoint used in 
the trials for our currently FDA-approved biologics: adalimumab, secukinumab, bimekizumab. Although this a meaningful threshold, I do not think it was ever meant to be the ceiling of what patients deserve. With HiSCR75, HiSCR90, and even HiSCR100, we are looking at 75%, 90%, and 100% reduction, which is so important for us to meet patients where they want to be. They do not want to just be halfway better; they typically want to be 100% better. This allows us to reset our expectations and have more direct conversations with patients about the depth of response. HiSCR50 is not the finish line. If patients have cleared half of their lesions but still have disease activity affecting their quality of life, that is not a success story to me, and I think most of the people in our community taking care of our patients with HS would agree.There are a lot of exciting data coming out at those higher endpoints. For example, the VELA-1 and VELA-2 trials for sonelokimab showed 62% of patients achieving HiSCR75 and up to 32% of patients achieving HiSCR100 at week 40. With povorcitinib, one of the novel oral JAK inhibitors we are looking at in HS, up to 71.4% of patients achieved HiSCR50, up to 57% achieved HiSCR75, and up to 29% achieved HiSCR100. This is some of the most comprehensive durability evidence yet for an oral HS therapy, which is huge. For bimekizumab, we now have 96-week data from the BE HEARD extension trial. Again, HiSCR50 at 85%, which is great, but we are seeing 77% of patients achieving HiSCR75, 58% with HiSCR90, and 44% with HiSCR100. This is the longest follow-up data available for HS. We have done it in other inflammatory conditions like psoriasis, but now that we are seeing some of those data in HS, it is so promising and meaningful to have something concrete to strive toward for our patients.

The Dermatologist: Among the emerging therapies, which mechanisms are most promising, and how might they reshape treatment strategies over the next 5 to 10 years?
Dr Barnes: I am biased in the sense that I think all the emerging therapies are exciting. I would not necessarily pick one over 
another at this time, but I think that the different pathways and mechanisms have some novelty that we can talk about. For oral JAK inhibitors, we have povorcitinib in the pipeline, which is new and specifically for HS, and upadacitinib, which is already approved for inflammatory bowel disease, rheumatoid arthritis, and atopic dermatitis, and now we are seeing what it looks like for HS. There is also a new topical JAK inhibitor option in phase 2/3 trials, topical ruxolitinib, which is promising for our patients with mild HS. Phase 2 trials showed about 79.2% of patients achieving HiSCR50 compared to the vehicle group, which is remarkable for a topical agent. These agents provide a major shift in the flexibility of how we can deliver treatment. Up until now, 
except for antibiotics, all our FDA-approved treatments for HS have been injectables.

As for some of the more novel therapies that we have not seen deployed in HS yet, I think the BTK inhibitor remibrutinib is exciting because it is already FDA approved for spontaneous urticaria and it could be valuable to patients who have not responded to upstream pathway inhibition or even for patients who have both conditions. Then there is the IRAK4 degrader LT-002-158. In 2023, there was an interesting paper published in Nature Medicine looking at that pathway in HS. It might be worthwhile to see if there is a new way of using protein degradation to potentially achieve deeper pathway suppression than some of our traditional inhibitors.Over the next decade, I think we are going to move forward to being able to have truly personalized treatment options, where we choose agents based on disease phenotypes and patient comorbidities instead of just simply stepping through treatments based on cost or what the insurance company wants us to do first. I think this pipeline is making such a future possible.

The Dermatologist: With financial barriers to therapeutic access a reality, what practical tips do you have for dermatologists trying to achieve the best outcomes for their patients with HS?
Dr Barnes: This is where science ultimately meets reality. And it is where I, and so many of my colleagues, spend a significant amount of our clinical energy. Often, failure in HS is not just a failure of biology; unfortunately, it is a breakdown in coverage, authorization, dispensing, and affordability. We must fight on all these fronts to get our patients the care they need and deserve. Partnering with a specialty pharmacy is key. There are great data out there showing that specialty pharmacy systems can get medications to patients a lot sooner than if the office is just doing it on their own. Most insurance plans have a designated specialty pharmacy, so working with them consistently is one of the fastest ways to get patients their medications. I am in an academic setting where our health system has its own specialty pharmacies and they are really good at streamlining how we can get medications covered for our patients with HS, saving enormous amounts of time—not only for the patient, but also for me so I can pour that energy into patient care instead of administrative burden.

Many of these medications do require prior authorization, so it is important to write a high-yield prior authorization the first time. Make sure that your documentation is thorough. This is where I encourage everyone to lean on the HS Foundation. They have an entire section dedicated to prior authorization templates that are thorough, well-cited, and clearly written. You can use those templates and personalize them with your patient’s disease history, severity, prior treatment failures, contraindications, and quality-of-life impact. And if you do get denied, do not give up. Many denials miss key clinical details. Make your appeal specific, prepare for peer-to-peer review, and clearly communicate why delays cause harm, such as progression to surgery, hospitalization, or emergency care.

Finally, screening for financial assistance programs is essential. Copay cards, bridge programs, and nonprofit resources can make these therapies accessible. It is not glamorous, but addressing these barriers is often the difference between a treatment plan that works and one that never gets started.