I. Introduction

Research into new drugs for hidradenitis suppurativa (HS) has greatly increased in the last 20 years. New drugs being studied in clinical trials may become good treatment options for helping treat HS in the future. This chapter explains the clinical trial process, what a drug target is, how HS occurs, and reviews the drugs being studied in clinical trials for HS (often called “the pipeline”).

II. What is a clinical trial?

Clinical trials test new drugs to see whether they are safe and effective for treating a given disease. There are four stages of clinical trials referred to as “phases”. Phase I trials test drug safety and look for harmful side effects. Phase II trials continue to evaluate safety and test whether a drug is effective at treating a specific disease, comparing people taking the drug being studied with people taking a “fake” drug (also called placebo group). Phase III trials test the effectiveness of drugs across larger and more diverse groups of people. In the United States, after the drug has been tested in Phase I through III trials, the drug may be approved by the Food and Drug Administration (FDA). Once a drug becomes approved by the FDA, doctors can prescribe the drug to patients, Phase IV trials take place after FDA approval and entail collecting more information as the drug is used by the larger general population. A detailed description of clinical trials Phases I-IV and a complete list of active clinical trials for HS can be found at clinicaltrials.gov

III. What is a drug target?

Drugs work by binding and blocking “targets” that cause disease. The most common drug targets are called ligands and receptors. Ligands are small proteins that tell cells to carry out certain tasks. Ligands convey a message to the cell by binding to their specific receptor on the cell surface. Through ligands and receptors, cells can talk to each other and carry out certain functions. Problems with ligands or receptors can lead to cells carrying out the wrong functions that may lead to disease.

The immune system is a complex network of cells and proteins that defend our body against sickness and disease. When prompted, immune system cells release ligands called cytokines that bind receptors on other cells. As a result, cells are told to turn on (or activate) inflammation to fight off disease. Our current understanding is that the immune system is overactive in HS, causing inflammation when it is not needed and harming healthy tissue. Drugs used to treat HS can bind to and block cytokines or receptors involved in this process, stopping the inflammation and damage to healthy tissues that we see in HS.

There are many types of drugs, and a general principle is that the structure of each drug determines its overall function. One type of drug is called an antibody. Antibodies are special proteins made by the immune system that recognizes and block harmful substances in the body, such as bacteria, viruses, and toxins. Antibodies can also be made in the laboratory and given as a drug to recognize and block disease-causing proteins. For instance, an antibody can be made to recognize and block a cytokine known to cause inflammation in HS. In this way, antibodies can be a good treatment for some patients with HS. Many drugs being made and studied for HS are antibodies and are given the ending to their name “-mab” (eg, adalimumab). Most antibody drugs are given as an injection or an infusion.

IV. How does HS develop?

Knowing how HS occurs in the body helps researchers decide what targets may be important for new HS drugs to block. The red lumps (“nodules”), boils (“abscesses”), and tunnels that form in HS are thought to start with a plugged hair follicle that widens and bursts open into the skin. Abnormal hair follicle structure, hormones, smoking, increased body weight, and chronic rubbing of the skin may play a role in the hair follicle plugging and bursting. Abnormal levels of bacteria living on the skin and in the hair follicles may also add to the inflammation seen in HS.

Bursting of the hair follicle in the skin starts a series of events that cause the skin to become red, warm, swollen, and painful. The material of the ruptured hair follicle activates cells called macrophages and dendritic cells. These important cells act as the “guards” of the immune system and release cytokines that produce inflammation. Some of these cytokines include tumor necrosis factor alpha (TNF-α) and interleukins (IL), such as IL-1 and IL-17. One of the major effects of these cytokines is calling white blood cells called neutrophils to the skin. Neutrophils normally reside in the blood stream but can travel to the skin if they are needed to help fight infection or cause inflammation. Neutrophils are the “first responder” cells and they both release toxic substances that may hurt tissues and call even more neutrophils into the skin. Pus forms as a result of neutrophils migrating to the skin and causing inflammation. Complement is another system used by the immune system to fight off infections. Proteins that are part of the complement system seem to be abnormally activated in HS. One protein involved in complement, called complement 5a (C5a), recruits even more neutrophils to the skin. The inflammation caused by neutrophils, cytokines, and complement lead to the nodules, abscesses, and draining tunnels seen in HS. Drugs that block the functions of neutrophils, cytokines, and complement may reduce the inflammation thought to cause HS.

V. Pipeline medical therapies

Drugs being studied in clinical trials for HS are described below based on the main target of each drug. Table 29.1 lists those clinical trials for HS that are active, recruiting, or not yet recruiting at clinicaltrials.gov as of April 1, 2025. Drugs being studied that do not yet have a formal name are typically identified by a combination of letters and numbers (eg, ABC-123). Figure 1 illustrates targets of new drugs that are being studied for HS. Drug names mentioned in this section that are currently being studied in clinical trials are underlined.

Neutrophils & Complement. As mentioned above, neutrophils are one of the cell types that are most active and destructive in HS. Large numbers of neutrophils are called to the skin by inflammatory cytokines and some fatty molecules, called lipids. An example of a lipid that recruits neutrophils to the skin is called LTB4. A new oral drug, called LYS006, stops cells from making LTB4 and therefore prevents neutrophils from migrating to the skin and causing inflammation. LYS006 is currently being studied for HS in a phase II trial.

Blocking the complement pathway can also reduce the number of neutrophils called to the skin. There are two drugs that have recently been studied for HS that block the complement pathway. BDB-001 is monoclonal antibody drug given as an injection that directly blocks C5a to lessen inflammation. Although detailed results have not been published, the study was completed without major safety concerns, and BDB-001 remains under consideration for future development. Two additional drugs that were previously studied for HS—Avacopan (an oral C5a receptor blocker) and IFX-1, also called vilobelimab (an injectable drug that blocks C5a itself), both showed improvement in phase II studies, but not significantly greater than placebo. However, makers of both Avacopan and IFX-1 are committed to further test whether these C5a blockers will be safe and effective for some HS patients.

Other drugs targeting neutrophil signaling include INF904 (an oral C5a receptor blocker currently in phase II trials), brensocatib (an oral DPP1 inhibitor), and eltreikibart (an IV antibody targeting CXCR1/2 chemokines), which are all in ongoing phase II studies. RIST4721, which also targeted CXCR2, was removed from the pipeline due to safety concerns.

Cytokines. Adalimumab is an antibody drug that is one of the three FDA-approved drug treatments for moderate to severe HS. TNF-α levels are increased in HS and adalimumab blocks this cytokine from causing inflammation in the skin. Infliximab is another antibody drug that blocks TNF-α that is FDA-approved for rheumatoid arthritis, plaque psoriasis, and inflammatory bowel disease. A small study of 33 patients showed that treatment with infliximab for 8 weeks significantly improved HS compared to placebo. Because of these results and positive results from other small studies, infliximab is sometimes prescribed when HS fails to improve with adalimumab. Though not currently FDA-approved for HS, the North American Clinical Management Guidelines for HS recommend that infliximab can be prescribed for moderate to severe disease. A new drug that is similar to infliximab, an infliximab biosimilar, has completed a phase I trial for HS; however, no publicly available data has been released to date.

Other cytokines involved in HS inflammation include IL-1, IL-17, and IL-36. There are several drugs in clinical trials that block these cytokines in attempt to stop the inflammation seen in HS.

IL-1 is a cytokine that causes inflammation and is found in high amounts in HS skin and blood. A small study showed that an IL-1 receptor blocker, Anakinra, was effective for HS. Since then, new treatments aimed at blocking IL-1 are in clinical trials for HS. Lutikizumab, a new antibody drug that binds IL-1 was recently developed and is being studied in phase II and III trials for HS. MAS825, an IL-1 blocker that also blocks IL-18, another cytokine, has previously been studied for COVID-19 infections, and is now in a phase II trial investigating its efficacy for HS. IRAK4 is a key signaling protein activated after IL-1 binds to its receptor, and it plays a central role in triggering the release of inflammatory molecules. Blocking IRAK4 may help interrupt the IL-1 signaling pathway and reduce inflammation. SAR444656 and LT-002-158 (oral), and EVO101 (topical) are IRAK4 inhibitors currently being studied in phase I/II  clinical trials for HS.

IL-17 is another key driver of inflammation in HS. The IL-17 cytokines are found in high amounts in HS skin and blood. Two IL-17 blockers–secukinumab and bimekizumab recently became FDA-approved treatments for moderate-to-severe HS. Large phase III trials of Secukinumab demonstrated that a significant number of patients treated with it experienced improvements in their HS compared with no treatment. Bimekizumab, a unique IL-17 blocker, also demonstrated positive results in phase III trials. Another IL-17 blocking drug, sonelokimab, is currently being studied in phase III trials. HB0043, a newer agent in early-stage development, blocks both IL-17 and IL-36. IL-36 is another cytokine found in high amounts in HS skin and is thought to contribute to the inflammatory process seen in HS. One antibody drug that blocks IL-36, called spesolimab, already FDA-approved for the treatment of a rare skin condition called generalized pustular psoriasis, is being studied in a phase II trial for HS. A different IL-36 blocker, imsidolimab, completed a small phase II trial in HS but did not show benefit over placebo. Other IL-36 inhibitors have completed phase II studies with results pending.

Janus Kinase. Janus kinases (JAKs) are proteins attached to many cytokine receptors and help relay messages from ligands and receptors to the inside of the cell. There are four different JAK proteins (called JAK1-3 and TYK2) that are attached to many kinds of cytokine receptors. The first FDA-approved JAK blocker drugs were tofacitinib (JAK1-3 blocker) and ruloxitinib (JAK1-2 blocker). Tofacitinib is FDA-approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. So far, there has only been a few reported cases of tofacitinib being effective for HS. Tofacitinib is currently under investigation studied in a phase II trial for multiple inflammatory conditions in patients with Down Syndrome, including HS. Povorcitinib, a new JAK1 blocker, has positive phase III trial results that were announced early 2025. Upadacitinib, a JAK1 blocker that is approved for other dermatology conditions such as atopic dermatitis, is currently being studied for HS in a phase III trial. Oral ruxolitinib is FDA-approved for the treatment of several bone marrow diseases. Ruloxitinib is also made as a topical medicine. Topical ruxolitinib is FDA-approved for atopic dermatitis and vitiligo and is currently being studied in a phase III trial for HS.

Various Immune Cells. Several of the new drugs in phase I and II trials block proteins and receptors that affect many different immune cells and pathways of inflammation. Fostamatanib, Remibrutinib, Zunsemetinib, and Orismilast, are all oral medications that affect the ability of various immune cells to function. Fostamatanib and Remibrutinib uniquely also affect B-cells, which produce antibodies. Zunsemetinib and Orismilast reduce the ability of immune cells to produce and respond to cytokines, specifically TNF-α and IL-1. While Orismilast reduces inflammation, it does not significantly reduce the immune system’s ability to fight off infections. For some people, this may make Orismilast more appealing than other anti-inflammatory drugs. Apremilast, a drug similar to Orismilast, has previously been shown to be effective for less severe HS. Iscalimab is a unique injectable drug that blocks a receptor needed to activate various immune system cells, including as macrophages and dendritic cells, as well as B-cells. AT193 is a topical medication that reduces the ability of immune cells to produce IL-17. PTM-001 is an oral receptor blocker that also influences IL-17 production, but more prominently affects cells’ ability to produce IL-1 as well as TNF-α. Anifrolumab, which blocks type I interferon receptors, is being studied in a phase II trial.

SBT777101 is a cell-based therapy (called CAR-Treg therapy) in early development. In this approach, a patient’s own regulatory T cells (Tregs)—a type of white blood cell that helps regulate the immune system, rather than trigger inflammation like many other types of white blood cells—are collected, engineered to recognize a specific protein involved in HS, expanded in the lab, and then returned to the patient to help regulate the immune response.

Other Drugs. Metformin, a drug that is FDA-approved for the treatment of type II diabetes mellitus, has shown promise for patients with HS in studies. Metformin works by boosting insulin sensitivity and lowering blood sugar, making it a very useful treatment for type II diabetes. Metformin is also thought to reduce inflammatory cytokines that cause disease in HS. A phase III clinical trial was completed to see if metformin could be a good treatment option for patients with HS, but results are not yet publicly available.

Table 29.2 lists the new non-drug treatments being studied in clinical trials for HS as of April 1, 2025. A detailed review of these treatments is outside the scope of this chapter.

The future of HS treatment appears bright with these promising new therapies being studied in clinical trials, and there is hope that more safe and effective treatment options will become available for patients soon.

VI. Reference articles

1. Zouboulis CC, Benhadou F, Byrd AS, et al. What causes hidradenitis supurativa? – 15 years after. Exp Dermatol. 2020;29(12):1154-1170.
2. Zouboulis CC, Frew JW, Giamareollos-Bourboulis EJ, et al. Target molecules for future hidradenitis suppurativa treatment. Exp Dermatol. 2021;30 Suppl 1:8-17.
3. Frew JW, Hawkes JE, Krueger JG. A systematic review and critical evaluation of inflammatory cytokine association in hidradenitis suppurativa. F1000Res. 2018; 7:1930.
4. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81(1):91-101.
5. Johann E Gudjonsson JE et al. Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis. JCI Insight 2020;5(19):e139930