A spotlight on hidradenitis suppurativa

By Allison Evans, Assistant Managing Editor, July 1, 2025

For many years, hidradenitis suppurativa (HS) has been an understudied disease that was poorly understood, making treatment difficult. While there is still much to be uncovered, researchers have made progress with a steady stream of literature being published on the disease as well as a multitude of new potential therapeutics in clinical trials.

“HS can be challenging to treat because we are limited in our treatments,” said Alexandra Charrow, MD, MBE, FAAD, director of the Hidradenitis Suppurativa and Neutrophilic Dermatosis Clinic, and assistant professor of dermatology at Harvard Medical School. “The best treatments right now are still not as good as the best treatments we have for psoriasis.”

In addition to a lack of therapeutic options, HS is a disease that occurs much deeper in the skin, so it can cause more scarring and disfigurement. “On top of all that, the disease itself is often very painful, and we as dermatologists are not always trained in how to treat pain as a component of skin disease,” Dr. Charrow added.

New guidelines in development

The Academy, along with the HS Foundation and the HS Expert Resource Group, is currently working on updated HS guidelines, which are expected to be published in JAAD within the next year or two. The most recent guidelines are from 2019, but a lot has changed since then, including the FDA approval of two new treatments that are available.

“My guess is that in the next few years, there will likely be a few more treatments that will be approved. There are at least six medications in phase 3 trials right now and a whole slew more in phase 2, so some of these medications are likely to be discussed in the upcoming guidelines,” Dr. Charrow noted.

Various treatments, including JAK inhibitors, are likely to be part of the updated guidelines even though they may not have the strongest recommendation until the phase 3 trials are complete, said Christopher Sayed, MD, FAAD, co-author of the 2019 HS guidelines, professor of dermatology at the University of North Carolina at Chapel Hill, and director of its HS clinic.

FDA-approved treatments

Biologic drugs have been a positive breakthrough for the treatment of HS where they have shown excellent results for other conditions like psoriasis. Adalimumab was the first FDA-approved treatment for HS in 2015 followed by secukinumab (IL-17A inhibitor) in 2023 and bimekizumab (IL-17A/IL-17F inhibitor) at the end of 2024.

“All three of these biologics are appropriate first-line therapeutic considerations for a patient with moderate-to-severe disease. Having more than one FDA-approved therapy was a game changer because as dermatologists treating HS, we want to know that we have different options for our patients,” said Jennifer Hsiao, MD, FAAD, associate professor of dermatology and director of the HS clinic at the University of Southern California, Los Angeles.

“When thinking about choosing which biologic to start, remember to take the patient’s comorbidities into account, such as inflammatory bowel disease or severe congestive heart failure. Something else to keep in mind is that adalimumab is approved down to the age of 12, whereas secukinumab and bimekizumab are currently only approved for patients ages 18 and up,” Dr. Hsiao said. Another thing to consider, she added, is a patient’s tolerance for frequency of injections. Adalimumab is injected at least every two weeks, and the other two biologics offer every four-week dosing. Ultimately, a patient’s insurance coverage may play a large role in determining which medications a patient can easily access as there may be step-therapy requirements.

“My guess is that in the next few years, there will likely be a few more treatments that will be approved.”

There haven’t been any head-to-head studies among the approved biologics, but secukinumab and bimekizumab target a separate inflammatory pathway than does adalimumab, which targets TNF-α, Dr. Sayed noted. “I think the efficacy of bimekizumab is probably a bit higher than the other two biologics, and it may have an edge, especially if you look at its one- and two-year data. The longer patients are on it, the more they seem to continue to improve, which is a major advantage.”

“While HiSCR50 (≥50% reduction in inflammatory nodules and abscesses) was the primary endpoint evaluated in the phase 3 trials, the secondary endpoints of HiSCR75 and HiSCR90 were the more impressive outcomes,” said Dr. Sayed. “These outcomes are much more closely linked to the level of true clinical meaningfulness and patient satisfaction.”

While most HS trials focus on outcomes at week 16, Dr. Sayed noted the sustained improvements seen in these studies, particularly looking at week 48 and week 96, where there is continued improvement over time.

“The depth of response that’s being seen with bimekizumab in the long-term studies is higher than what was seen in previous phase 3 trials,” Dr. Hsiao added.

Patient response to biologics

“While there is a place for all three biologics, the two newer treatments tend to be less immunosuppressive and may be slightly more effective than adalimumab in the long term, but they are slower to work,” Dr. Charrow noted. “Patients often lose response to adalimumab over time, while two-year data for the newest biologics look optimistic,” she added.

With adalimumab, there are patients who have an inadequate response or who lose their response over time. “Before approvals of these newer biologics, it would automatically mean a huge battle with insurance for off-label treatments,” Dr. Hsiao said.

“The majority of patients really don’t respond well to TNF inhibitors over time,” Dr. Sayed agreed. “There’s a need for more therapies to be available, so we have a broader variety to treat patients with, but also treatments that push the bar forward when it comes to how good those responses actually are.”

There isn’t a way to predict which patients will respond best to which drug at this point, although comorbidities certainly play a role. “Sometimes we have a patient with bad pyoderma gangrenosum or inflammatory bowel disease where we know we’re going to prefer a TNF inhibitor over an IL-17 inhibitor,” Dr. Sayed said.

While there may be a bit of a guess-and-test approach to deciding on which biologic to start with, they’re not appropriate for everybody. “If you have MS or heart failure, or are prone to non-cutaneous infections or have an active malignancy, adalimumab would likely not be an appropriate choice,” Dr. Charrow added.

“Having these new approved biologics makes it easier to get a medication approved without fighting insurance or having to go off-label,” Dr. Sayed said. “If a medicine stops working, we have good backups ready to go.”

Other potential biologic options

For patients with more advanced disease, dermatologists often have to reach for other treatments like infliximab, which is not FDA approved for treatment of HS. According to Dr. Hsiao, there is published data to support that infliximab infusions can be pushed to high frequency, high doses for HS such as 10mg/kg every 4 weeks (doi: 10.1016/j.jaad.2019.05.022). “This is an important update because hopefully insurance will be more likely to allow us to use it when we ask for it.”

“Sometimes we still must use the biologics that are FDA-approved in conjunction with other treatments,” Dr. Charrow remarked. “For patients with milder disease, they may be fine without a biologic. But for patients with moderate-to-severe disease, it may be a biologic plus surgery plus maybe an antibiotic plus maybe hormonal treatment.”

Despite having positive results in inflammatory bowel disease and psoriasis trials, IL-23 inhibitors have not had successful phase 2 trials in HS. Phase 2 trials of the IL-23 inhibitors risankizumab and guselkumab in HS did not demonstrate efficacy over placebo. “The placebo rates were high, and so there wasn’t a statistically significant difference seen between the study drug versus placebo,” Dr. Hsiao said.

However, more data are now being published evaluating whether there are certain patient characteristics that might predict a better response to IL-23 inhibitors. “I still use these agents, though more as an adjunct therapy rather than monotherapy for a patient with recalcitrant disease,” she added.

“We’re still trying to figure out why a treatment like risankizumab works so well for psoriasis and IBD but does not seem very effective in HS, whereas other treatments can overlap and treat many of those conditions,” Dr. Sayed noted.

Coming down the pipeline

“It’s really an exciting time for HS because it’s a mystery that’s being solved thanks to the amazing work of dedicated scientists and patient advocates,” Dr. Charrow said. There are many drugs currently being studied for HS, with at least six in phase 3 trials.

Of the drugs in phase 3 trials, there are four new mechanisms of action being explored, Dr. Hsiao added.

The drug that is furthest along in clinical trials is povorcitinib, an oral JAK1 inhibitor. In March, topline data were announced from two pivotal phase 3 trials evaluating the drug in adults with moderate-to-severe HS. “It’s currently not approved for other indications yet, and it will be a nice option because it will be a pill as opposed to an injection,” Dr. Sayed said. “It will also have a new mechanism of action, which means that some patients who don’t respond to the other treatments may respond to this one.”

The trial results showed a greater percentage of povorcitinib-treated patients — at both 45 mg and 75 mg — achieved HiSCR50 (defined as ≥50% reduction from baseline in the total abscess and inflammatory nodule count at week 12 with no increase in abscesses or draining tunnels) compared with placebo at week 12. In patients previously treated with biologics, povorcitinib was also associated with greater achievement of HiSCR50 vs. placebo.

“The FDA approval of povorcitinib is likely a year-and-a-half to two years away, so we’ll have a gap after the back-to-back approvals of secukinumab and bimekizumab,” Dr. Sayed noted. “Two or three years from now, we’ll see the next wave of new therapeutics hit.” Upadacitinib, also a JAK1 inhibitor, currently has an ongoing phase 3 trial.

Remibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, is currently in phase 3 trials. “Remibrutinib is important for dermatologists to know about because it’s already had positive phase 3 trial results for chronic spontaneous urticaria, and FDA approval for that indication may be coming later this year,” Dr. Hsiao said.

IL-17 small molecules or nanobodies — sonelokimab and izokibep — are both in phase 3 trials. “An exciting thing about sonelokimab is that they have an ongoing adolescent study, age 12 to 17 years. The adolescent approval for adalimumab was done based on pharmacokinetic modeling whereas this is a dedicated trial for adolescents,” Dr. Hsiao said.

“Investigational drug, lutikizumab, an IL-1α/β inhibitor, has shown positive results in phase 2 trials — and has advanced to phase 3 trials — for patients with moderate-to-severe HS who have failed anti-TNF therapy,” Dr. Charrow explained.

“It was somewhat surprising that lutikizumab had such promising phase 2 results since there have been a few IL-1 antagonists that have failed to see adequate responses in clinical trials for HS,” Dr. Sayed said.

“My hope is that in the next five years, we’ll see drugs that aren’t just repurposed from other conditions that people hope work, but drugs that are developed with that pathophysiology in mind,” he added. “This would be a real shift from HS being second, third, fourth in line for a drug trial.”

Surgical procedures

Despite a burst of therapeutic potential, inevitably some patients do not respond to these treatments alone, and so surgery may be employed as an adjunct option. “Most HS specialists would recommend that patients who have tunnels or persistent abscesses get them removed surgically by a dermatologist in addition to continuing medical treatment,” Dr. Charrow said.

“There’s been more uptake of dermatologists performing excisions and de-roofing procedures and better evidence for their use in conjunction with biologics,” Dr. Sayed said. That knowledge and training is being disseminated much more widely.

“With a dermatologist’s skill set, they can absolutely deroof or excise a persistent HS lesion, like a tunnel. All you need are the tools on your standard excision tray. There are very high rates of patient satisfaction when these procedures are done,” Dr. Hsiao said.

“When a patient comes in with a large abscess, instead of using a No. 11 blade for incision, you can use a 4-8 mm punch tool, so that the abscess doesn’t reform immediately. You numb the abscess, drain it, and do not pack it,” she recommended.

In general, recurrence rates from HS deroofing/excisions are low. “The rate of recurrence in the armpits is very low — below 10%, while in the groin, it is around 25%,” Dr. Charrow said. “The likelihood that spot will recur in the place where you removed it is really low, but that doesn’t stop new spots from forming, so that’s where maintenance medication comes into play.”

While there haven’t been any large-scale studies investigating new procedural techniques, there have been some smaller studies published about other non-surgical procedures. Some of these procedures under investigation include botulinum toxin injections; sclerotherapy (injecting hypertonic saline into the sinus tracts or tunnels) or other substances that could potentially be injected to help tunnels resolve; laser treatments; and cryoinsufflation, where you spray liquid nitrogen into the tunnels to help reduce inflammation and scarring. “Cryoinsufflation has been associated with some complications, so it isn’t widely used,” Dr. Sayed said.

There have been several good quality studies published demonstrating the efficacy of laser hair removal for the treatment of HS. “While it’s ideal for early treatment, it can benefit patients with more severe disease on a particular body part. It’s just a matter of getting regulatory agencies and insurance companies to support its use on a wider basis,” Dr. Sayed added.

A multimodal approach

“It’s important to continue medical management when you perform HS procedures because there may not be recurrence in that area that you deroofed or excised, but you need medical management to mitigate disease progression and occurrence of new lesions,” Dr. Hsiao noted. “HS is a condition that needs a multimodal approach, whether combining different medications or combining medical and procedural therapies.”

“Even as good as the medicines get, there will be a continued role for surgery because a physical remodeling of the skin happens for a lot of patients where the tunnels and scars that develop can’t be erased because you turn the inflammation off,” Dr. Sayed said.

“Being able to make sure you can recognize when it is useful to perform surgery is going to be a huge factor in getting patients the best they can be over time. It also means that the longer we wait to intervene, the more surgery must get done and the more irreversible the damage done by the disease. The earlier you intervene, the more you prevent that irreversible destruction from happening,” he continued.

“Ultimately, early diagnosis and management of HS is key,” Dr. Hsiao said. “We don’t need to wait for a patient to have painful, draining tunnels before we decide that they’re a candidate for biologic treatment. Timely intervention is needed to improve our HS patients’ quality of life and their disease trajectory.”

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