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Hidradenitis suppurativa in axillary mass tissue under microscope, pink and purple
Hidradenitis suppurativa (HS) Learning Zone

HS treatment

Last updated: 23rd Jan 2025
Published: 15th Sep 2021
Declaration of sponsorship: Novartis Pharma AG
Hidradenitis Suppurativa – Overview

Unmet needs in HS

The significant diagnostic delay of hidradenitis suppurativa (HS), in addition to the unpredictability of the disease and its response to treatment, has led to a number of unmet needs1.

An understanding of these unmet needs is essential for creating multidisciplinary approaches to care, developing new treatments, guiding research, and supporting patients1.

Dr Joslyn Kirby provides an overview of the unmet needs for people with HS.

What are unmet needs in the life impact and comorbidities of HS?

To determine the unmet needs of people with HS, the Global Survey Of Impact and Healthcare Needs (Global VOICE) project (N=1,299) carried out the largest and most comprehensive multinational study of patient perspectives1.

In the study, a large proportion of people with HS reported a moderate-to-extreme and domain-specific impact on their life caused by the disease1. Moreover, 10% of patients reported being unable to find employment and 15% considered themselves disabled and unable to work1. Factors that were associated with worse quality of life (QoL) for people with HS included disability, increasing number of comorbidities, and difficulty getting access to a dermatologist2.

Regarding treatment, the Global VOICE project found that nearly half of patients were dissatisfied with their current treatment3. A smaller study on unmet needs in people with HS reported that 47% found the referral process ‘very difficult’ and although biologics improved symptoms in 63% of patients, time to receiving treatment was >2 years for 41% of patients4.

A recent qualitative study showed that barriers to accessing care perceived by people with HS were associated with employment, healthcare coverage, the professional attributes of healthcare professionals (HCPs), and characteristics of the healthcare system5.

HS can have a large impact on life, such as reduced enjoyment of activities, independence, self-esteem, and body image as well as increased stigmatisation and isolation6–8

The need to appropriately assess the psychological burden of HS and its impact on QoL is clear. The Dermatology Life Quality Index (DLQI) is widely used in HS but may not reflect the disease-specific impairments9. Several disease-specific QoL measures have been proposed, including10,11:

  • HSBOD (Hidradenitis Suppurativa Burden of Disease)
  • HiSQOL (Hidradenitis Suppurativa Quality of Life)
  • HSQoL-24 (Hidradenitis Suppurativa Quality of Life-24)
  • HIDRAdisk
  • HSIA (Hidradenitis Suppurativa Impact Assessment)
  • eHSSDD (electronic Hidradenitis Suppurativa Symptom Daily Diary)
  • eHSSQ (electronic Hidradenitis Suppurativa Symptom Questionnaire)
  • eHiSQOL (electronic Hidradenitis Suppurativa Quality of Life questionnaire)

While these disease-specific measures have had some initial validation, there is a lack of experience of their use, and wider validation studies are required9. Therefore, one of many unmet needs in HS is to further develop and implement disease-specific QoL measures10 (Table 1)1.

Table 1: Unmet needs of people with hidradenitis suppurativa and potential mechanisms to address them (Adapted1). POC, point-of-care; QoL, quality of life.

Domain Unmet need Potential mechanisms to address unmet needs
Life impact and comorbid conditions Life impact assessment • Disease-specific QoL instrument to measure life impact
Mental wellness • Address psychosocial impact of the disease through interdisciplinary care with mental health professionals
Diagnosis and disease awareness Disease awareness • Promote advocacy and interdisciplinary education with patient support groups and medical organisations
• Research and peer-reviewed publication
Delay in diagnosis • Develop POC diagnostics to help distinguish abscess and inflamed epidermal cysts by non-dermatologists
• Promote the role of the dermatologist in diagnosis and management
Quality and cost of care • Improve dermatology access to manage disease flares
Associated diseases • Identify associated conditions, their related mechanisms, and their modification with treatment
• Develop guidelines with recommendations for prevention and screening of associated conditions
• Establish interdisciplinary care teams to provide comprehensive care
Treatment and management Safe and effective treatment • Develop reliable and feasible tools to measure disease
• Develop relevant outcome measures to assess treatment efficacy
• Advance research to identify disease mechanism and potential therapeutic targets
• Develop medical treatments with improved efficacy and safety profiles
• Evaluate outcomes for procedural treatments
• Develop guidelines for pain management
Control of symptoms • Develop appropriate and effective strategies to address pain, drainage, odour, fatigue, and flare

Mental wellness

There is an important unmet need to address the psychosocial concerns associated with HS1.

Mood disorders are likely due to the physical and psychosocial impact of the disease, resulting in a reduction in QoL1

More than 30% of patients in the Global VOICE project reported depression or anxiety, with mood disorders in general being the most common comorbidity. Notably, around 9% of patients reported suicidal ideation or a suicide attempt. Considering the known association between HS and suicide deaths, this high frequency is a significant issue1.

Coping and resilience strategies, as well as interdisciplinary care with mental health professionals, may help to alleviate some of these concerns (Table 1)1.

What are the unmet needs in diagnosing HS and screening for comorbidities?

Addressing the unmet need of diagnostic delay for people with HS is essential (Table 1)1.

In the Global VOICE project, patients experienced an average 10-year delay to diagnosis despite approximately half of patients reporting disease flares (new or substantial worsening of signs or symptoms) daily or weekly, and over 80% experiencing flares at least monthly1,12. This is in addition to approximately 25% visiting an emergency department and 16% needing hospitalisation a minimum of four to five times for acute symptoms1.

Underdiagnosis may be in part due to a general lack of disease awareness in HS in addition to comorbidities1

A social media monitoring study in the USA and Europe has provided insights into the real-world experience of people with HS, suggesting a need for greater awareness of HS among HCPs13. Lack of awareness of HS among HCPs is a key factor contributing to delayed and missed diagnoses13. This important knowledge gap is highlighted in results from a recent qualitative survey, in which a large majority of HCP respondents (N=65) reported a lack of confidence in HS diagnosis and various aspects of HS management14 .

In a qualitative survey-based study (N=65), less than 30% of HCP respondents reported ‘strongly agree’ to feeling confident about diagnosing HS; furthermore, less than half reported ‘strongly agree’ to feeling confident about referring patients with HS patients to the appropriate speciality provider14

In the Global VOICE project, over 80% of patients reported having a comorbid condition. Recommendations for assessing comorbidities in people with HS were previously lacking and represented an unmet need. However, comorbidity screening guidelines have recently been published15. These detail the comorbidities that should be screened and recommend the screening method and frequency for each, as well as if the screening should be performed by the dermatologist, primary care physician or other specialists15.

What are the unmet needs in treating and managing HS?

A further unmet need for people with HS is the development of appropriate and effective pain management strategies1.

In the Global VOICE project, 90% of participants had experienced recent acute pain and 60% described the pain as moderate to worst possible1. Patients can also suffer from chronic pain, which can have a significant impact on QoL, as evident by nearly 4% of Global VOICE participants reporting substance use1. Unfortunately, strategies for addressing pain are not well established and can be highly variable1.

Participants in the Global VOICE project reported poor efficacy and undesirable adverse effects as being the most common causes of treatment dissatisfaction1

Approximately 30% of Global VOICE participants were also dissatisfied with procedural treatments, and nearly 50% expressed low optimism for controlling their symptoms in the future1.

A real-world study of HS in the USA and Europe has also revealed ongoing unmet needs for moderate-to-severe disease with a partial or lack of response to biologic therapy7. The results of this study highlight the need for novel treatments with better response rates to reduce disease burden in moderate-to-severe HS7.

HS treatment goals

Current treatment of hidradenitis suppurativa (HS) comprises several types of medication and surgical management based on the individual subjective impact and objective severity of the disease. The aims of treatment include improving quality of life (QoL) by limiting the incidence and duration of flares, reducing inflammation and suppuration, and relieving pain (Figure 1)8,16,17.


Dr Joslyn Kirby discusses the treatment goals of HS, including the reduction of symptoms and long-term control.

Reducing the symptoms of HS

The aim of treatment is to prevent new lesions, reduce the extent and progression of the disease, and decrease overall symptom burden18. HS treatment can be considered in three phases: (1) medical management to reduce disease activity, (2) surgical intervention for persistent areas despite medical management, and (3) long-term medication for postoperative management18.

A wide range of medications can be used to reduce flares, manage pain, and improve QoL, including16:

  • Antibiotics (to reduce inflammation and manage the microbiome)
  • Biologics (to target the pathophysiology and reduce inflammation)
  • Corticosteroids (to reduce inflammation)
  • Hormones (to reduce androgen effects on symptoms)
  • Retinoids (to reduce inflammation and heal lesions)
  • Topical and intralesional therapies (to aid healing and soften/shed scaly skin)

To heal wounds, a mixture of local wound care and oral antibiotics is recommended5,6. This can include antiseptic washes, negative-pressure wound therapy, or antibiotics applied to the skin or wounds5,6.

Typically, surgical interventions cure HS lesions locally, through the removal of irreversibly damaged skin. However, remaining dermal sinus tracts or tunnels may lead to recurrence, and active disease can lead to the development of new lesions. Alternatively, systemic treatment with anti-inflammatory antibiotics may reduce the need for surgery by19,20:

  • Lowering disease activity (such as inflammation and pain)
  • Reducing the size of the affected area

Anti-inflammatory treatment is therefore recommended at Hurley stage 2 and above, and should be implemented and optimised before surgery19,20.

As a final note, encouraging patients to implement health behaviour (or ‘lifestyle’) changes as part of their care is an important aspect of patient engagement, and can contribute to HS symptom reduction21,22. For example, smoking cessation and weight loss are important considerations for symptom reduction23 and are included in several HS guidelines8,24-27. Furthermore, results from a survey-based study (N=591) show that smoking cessation and substantial weight loss were associated with subjective and objective reduction in symptom severity22. Advising patients to avoid wearing rough and tight-fitting clothing, especially those produced from nonbreathing materials, such as polyester and nylon, may also be advisable since there is evidence suggesting that this type of clothing can result in lesion formation28.

Diagram displaying the two key treatment goals for improving the quality of life for people with hidradenitis suppurativa: relieving symptoms and relieving pain. The symptoms of hidradenitis suppurativa have a profoundly negative impact on quality of life, and up to 97% of people report being affected by pain associated with the disease.

Figure 1. Treatment goals for hidradenitis suppurativa8,16,29,30

Relieving pain in HS

Pain is a significant factor of HS that reduces QoL31. European and North American guidelines recommend an individualised treatment plan provided by a variety of healthcare professionals (HCPs), including5,6:

  • Dermatologists
  • Pain specialists
  • Psychologists

Treatments for acute pain can include topical analgesics, oral nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, as well as cautiously prescribed short-acting opioids32. Opioids and anticonvulsants are recommended for chronic pain8,16.

An algorithm proposed for the treatment of pain in HS suggests paracetamol and/or a topical NSAID for mild acute (and nociceptive) pain, and systemic NSAIDs or triamcinolone if pain persists33. For severe acute pain, opioids such as tramadol may be considered under guidance of a pain specialist. For nociceptive chronic pain, NSAIDs are recommended as first-line options, with duloxetine and nortriptyline as second-line options. For neuropathic chronic pain, gabapentin and/or duloxetine are suggested to be used as first-line treatment, and pregabalin, venlafaxine, and nortriptyline are second-line options33.

Is there a recommended treatment algorithm for HS?

Recommendations include medical management in the early states and the use of surgery as early as possible following the formation of abscesses, fistulas, scars, and sinus tracts8,24.

Many algorithms for the treatment of HS have been proposed25. Of these, three notable algorithms use variations of Hurley staging:

  • The European S1 guideline (2015) by Zouboulis et al.8
  • Evidenced-based approach to treatment (2016) by Gulliver et al.26
  • Hurley staging refined (2017) by Horváth et al. – The Dutch expert group27

The algorithms suggested by the European S1 guidelines and by Gulliver et al. both use the original Hurley staging system combined with evidence-based treatment options8,25.

A later proposed algorithm is the treatment ladder by Horváth et al., which uses a refined Hurley staging system that takes into account both the presence and amount of inflammation as a factor for making treatment decisions36.

Following assessment with the Hurley staging system, various options for lifestyle changes, medication, and surgical management can be considered depending on the impact and severity of the disease8,16.

How can long-term control be achieved in HS?

Personalised medicine, through the use of patient characteristics such as demographics, disease phenotype, and pharmacogenetics, may be a future strategy for predicting response to treatment in HS37.

Long-term control of HS requires outcome measures that are simple, quick, and validated, in order to define treatment response37

Many physician-reported and patient-reported outcome measures have been developed for HS; however, validation of these measures has been lacking and, until recently, there has been no consensus on which of these are best suited to clinical practice38.

The HS Core Outcomes Set International Collaboration (HiSTORIC) consensus statement recommends the use of the HS Investigator Global Assessment (HS-IGA), a physician-reported outcome measure, in clinical practice. The HiSQOL score was the recommended patient-reported outcome measure for clinical practice, with a 3-month assessment interval endorsed for both38.

Long-term control of HS can also be improved through enhanced patient education. In multiple conditions, improved patient knowledge has repeatedly been linked to improved use of health services, improved treatment adherence, better clinical outcomes, and improvements in patient QoL, compared with patients who lack knowledge of their condition39.

In a randomised controlled trial, people with HS preferred the addition of a written action plan created by their HCP in addition to a verbal consultation, reporting that it decreased confusion about adjusting treatments according to disease severity and helped to understand the treatment regime40. A cross-sectional survey in an online patient support group revealed that a handbook on HS for patients increased their satisfaction with the treatment process39.

Patient-centred care in HS

Shared decision-making

In addition to patient education, shared decision-making is an important element in patient-centred care. Patient-centred care is widely considered a gold standard in improving the quality of care for chronic diseases such as HS, and is also an effective strategy for facilitating knowledge translation between patients and their HCPs41.

In a qualitative study (N=21) involving interviews with adults living with HS, respondents described positive healthcare experiences when HCPs demonstrated empathy and active listening in their communication approach, as well as inquiring about patients’ goals with regard to their care42. Furthermore, respondents valued transparency around treatment expectations and outcomes, reporting that this facilitated the shared decision-making process42.

Discrepancies between patient and HCP definitions of disease terminology can act as communication ‘gaps’ and can impact the shared decision-making process. Definitions of a ‘flare’ in the context of HS is one example of such discrepancies: what patients consider to be a flare will vary from person to person, and patient definitions can also differ from clinical descriptions referred to by HCPs18. It is therefore recommended that clinicians ask their patients how they define a flare, to ensure clear communication and facilitate shared decision-making with the aim of improving treatment outcomes18.

Holistic care

The psychosocial impact of HS is very high and yet is underappreciated by clinicians42,43. As part of the patient-centred approach to healthcare, it is important for dermatologists to treat patients from a holistic standpoint that also encompasses emotional symptom management and provides mental health support44.

All patients should be referred to their local HS Foundation for access to educational materials and local or online patient support groups43. Support groups can help patients overcome feelings of loneliness and enable the sharing of coping strategies, and dermatologists should consider setting up their own local support groups. Patients who make use of support groups report a high perceived support score relating to their family and the larger patient community43.

In addition, screening patients for impacted psychosocial subdomains, including depression, anxiety, body image, sexuality, and financial strain, can improve patients’ QoL43. Depending on the subdomain(s) affected, the patient can be referred to a psychiatrist, therapist, and/or social worker43.

Treatment options for HS

Hidradenitis suppurativa (HS) is lifelong, recurring and difficult to manage. Early recognition and treatment are essential for preventing progression of the disease. Treatment should be tailored to the patient, with medications in early stages followed by surgery in more severe cases16,17. A combination of medical and surgical treatment may be used as part of a treat-to-target approach to optimise management45.


Dr Joslyn Kirby summarises the treatment options that are currently available for people with HS.

What lifestyle changes can help to manage HS?

Outside of medication and surgery, a variety of lifestyle changes have been shown to positively impact HS disease activity and severity46-49.

Smoking cessation

It is widely known that active smokers have a poorer long-term prognosis than non-smokers or former smokers46,47. However, there is conflicting evidence regarding the relationship between smoking and HS incidence or severity50.

On the other hand, there is evidence supporting the link between smoking status and treatment response: in a study by Kromann et al. (N=212), it was shown that 49% of former smokers and non-smokers reported remission of HS, compared with 29% of active smokers, after a median follow-up of 22 years47.

Similarly, results from a single-centre retrospective cohort study (N=198) show that people with HS who had a current non-smoker status were at a 2.634 times increased odds (95% CI, 1.301–5.332; P=0.007) of having a positive response to first-line treatment, compared with those who were current smokers51.

Despite the current lack of consistent evidence for smoking cessation being associated with HS improvement, the general expert consensus is that cigarette smoking should be avoided8.

Weight loss

There is a positive correlation between BMI and disease severity in people with HS49. A retrospective study (N=383) showed that 2 years after receiving bariatric surgery, 49% of patients reported no symptoms, 20% reported less activity, 20% reported no change, and 11% experienced an increase in disease activity48. Likewise, a systematic literature review of nine observational studies found that patient-controlled weight loss and bariatric surgery are both associated with HS regression52.

Are there topical treatments for HS?

Topical treatments available for mild inflammatory HS include clindamycin lotion, antiseptic skin cleansers, and resorcinol cream16.

Topical clindamycin is often the first-line therapy for mild-to-moderate HS, with evidence from multiple clinical trials supporting its safety and efficacy. A small double-blind randomised control trial (N=30) of patients with Hurley stage 1 and 2 HS showed a reduction in nodules, abscesses, and pustules following 3 months of daily topical clindamycin53. Further studies have also shown that clindamycin can reduce pain after 16 weeks54.

However, there is growing evidence that these antibiotic-based treatments may be contributing to antibiotic resistance55,56. In a cross-sectional analysis of 239 patients, a higher proportion of those who had used topical clindamycin had antibiotic-resistant strains of Staphylococcus aureus than those using no antibiotics; however, no significant antibiotic resistance was seen following oral clindamycin therapy55,56.

Combining topical clindamycin with antiseptic skin cleansers can be effective in preventing bacterial resistance, and a combination of clindamycin and benzoyl peroxide showed efficacy in a 2023 pilot trial with HS57. Other topical skin cleansers have not been studied in clinical trials with HS; however, expert opinion supports the use of chlorhexidine, azelaic acid, and zinc pyrithione8,16,58.

Resorcinol cream is recommended as a more targeted approach than clindamycin for long-term HS treatment55. Resorcinol cream has a keratolytic effect and mild antiseptic properties59. In an open study (N=32) of patients with Hurley stage 1 and 2 disease applying resorcinol (15%) twice daily for 30 days, 19% achieved clinical resolution of a treated boil after 7 days, and 84% after 30 days60. In a larger study investigating patient satisfaction with 15% resorcinol treatment, 84.8% of patients were highly satisfied with treatment based on effectiveness and side effects61.

What systemic treatments are there for HS?

In patients with inflammation and suppuration, treatment with oral anti-inflammatory antibiotics has been a mainstay35.

Most guidelines recommend a tetracycline antibiotic as first-line therapy for mild-to-moderate disease35,58,62. These include doxycycline and minocycline, which are known to inhibit neutrophilic migration, chemotaxis, and angiogenesis, and upregulate interleukin (IL)-10, in addition to their antibiotic properties63.

Clindamycin and rifampicin used in combination have generally been recommended as first-line treatment for moderate-to-severe HS, or as second-line treatment for mild disease35,58,62. However, some studies have shown that rifampicin induces enzymatic clearance of clindamycin, and clindamycin alone may be as effective as the combination64-66. Rifampicin monotherapy should be avoided because of implications for tuberculosis treatment and the risk of antibiotic resistance67.

Third-line antibiotic options include dapsone or triple combination therapy with moxifloxacin, metronidazole, and rifampicin35,58,62. Most guidelines suggest oral antibiotic treatment for up to 12 weeks35.

Intravenous antibiotics, such as ertapenem or ceftriaxone, may be used as induction treatment before oral antibiotics for people with severe refractory disease, or as a bridge to surgical intervention35,58.

Are any biologics approved for HS?

For people with moderate-to-severe HS in whom antibiotic treatment is ineffective, biologics are an alternative treatment option that can be used for prolonged periods59.

Currently, adalimumab, secukinumab, and bimekizumab are the only biologics approved for the treatment of HS68-73

Adalimumab, a tumour necrosis factor alpha (TNF-α) inhibitor, was the first biologic to be approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2015 for the treatment of HS in people aged 12 years and older70,71. For the European indication, this is specifically for patients with disease that has not responded to conventional systemic therapy, and patients should use a topical antiseptic wash daily during treatment with adalimumab70.

Secukinumab, an IL-17A inhibitor, was approved by the U.S. FDA and EMA in 2023 for the treatment of HS in adults68,69. Similarly to adalimumab, the European indication for secukinumab highlights its use in patients with disease that has not responded to conventional systemic therapy68.

Most recently, bimekizumab was approved by the EMA and the FDA in 2024 for adults with moderate-to-severe HS72,73. This novel monoclonal IgG1 antibody is the first to selectively inhibit both interleukin (IL)-17F and IL-17A74. For the European indication, this is specifically for patients with disease that has not adequately responded to conventional systemic therapy72.

Adalimumab

In 2012, a phase 2 parallel, randomised controlled trial (Table 3), showed that clinical efficacy after 12 weeks was achieved by a significantly greater (P=0.025) number of patients receiving 40 mg adalimumab (17.6%) than the 40 mg every other week group (9.6%) or placebo (3.9%)75.

The efficacy of the adalimumab 40 mg weekly dose led to two substantial phase 3 trials – PIONEER I and PIONEER ΙΙ75,76

Following these results, the PIONEER I and PIONEER II trials were carried out. In these trials it was found that the clinical response rate, defined by HS clinical response (HiSCR), was significantly higher in the adalimumab weekly groups at week 12 in PIONEER I (41.8% vs 26.0%; P=0.003) and PIONEER II (58.9% vs 27.6%; P<0.001) compared with placebο76.

In both studies, incision and drainage, or injection of intralesional triamcinolone acetonide suspension, were allowed. However, in PIONEER I, oral antibiotics were restricted, while in PIONEER II, a stable dose of antibiotics was allowed76. PIONEER II revealed adalimumab to significantly reduce the number of abscesses and inflammatory nodules in patients, while no reduction was observed in the antibiotic-restricted PIONEER I trial76.

Studies have also shown that systemic treatment with adalimumab in combination with surgery improves clinical outcomes and quality of life77,78.

Hear more about one of these studies, the SHARPS trial, here.

Secukinumab

The efficacy, safety, and tolerability of secukinumab have been evaluated in two identical double-blind phase 3 trials of people with moderate-to-severe HS, labelled SUNSHINE and SUNRISE (N=676 and 687, respectively)79. Participants were given 300 mg secukinumab subcutaneously (after standard weekly loading doses) every 2 or 4 weeks for up to 52 weeks, or placebo. The primary endpoint was clinical response at week 1679.

A significantly higher number of people who received secukinumab every 2 weeks achieved a HiSCR, compared with those who received placebo at week 16, across both the SUNSHINE and SUNRISE trials (45% vs 34% [P=0.0070] and 42% vs 31% [P=0.015], respectively)79

For those who received secukinumab every 4 weeks, the response for achieving HiSCR was superior to placebo in the SUNRISE study (46% vs 31% [P=0.0022]), but not in the SUNSHINE study (42% vs 34% [P=0.042]). Responses were sustained up to the end of the trials at week 52. Treatment with secukinumab was well tolerated, consistent with the safety profile of secukinumab for other indications, and no new safety signals were observed79.

Bimekizumab

The efficacy and safety of bimekizumab in adults with moderate-to-severe HS were evaluated in two phase 3 multicentre, randomised, double-blind, and placebo-controlled trials: BE HEARD I and BE HEARD II74. The two trials were identically designed and compared bimekizumab (320 mg) administered every 2 or 4 weeks, against placebo.

The primary efficacy outcome for these trials was achieving a clinical response of ≥50% defined by HiSCR (HiSCR50) at week 16. This outcome was met in both trials: the clinical response rate was significantly higher in the bimekizumab groups versus placebo at week 16 (BE HEARD I: 48% vs 29%, P=0.0060; BE HEARD II: 52% vs 32%, P=0.0032). Furthermore, these responses were maintained or increased between week 16 and week 48, during which all participants remained on or switched to bimekizumab74.

A significantly higher number of participants who received bimekizumab achieved HiSCR50 at week 16, compared with those who received placebo, across both the BE HEARD I and BE HEARD II trials (48% vs 29% and 52% vs 32%, respectively)74

Serious treatment-emergent adverse events were reported in 8% and 5% of participants over 48 weeks in BE HEARD I and BE HEARD II, respectively74. Overall, bimekizumab had a tolerable safety profile with no new safety signals; furthermore, its safety profile was consistent with safety data from previous trials across indications74.

What non-pharmacological treatments are there for HS?

Various laser and light-based treatments have been investigated for the treatment of HS, including59,80:

  • Laser hair removal with neodymium-doped yttrium aluminium garnet (Nd:YAG), Alexandrite, and diode lasers
  • Hair removal with intense pulsed light (IPL)
  • CO2 laser

Hair-removal therapies, including IPL and Nd:YAG, Alexandrite, and diode lasers, have proven useful and use selective photothermolysis targeting haemoglobin (resulting in an anti-inflammatory effect) or melanin (destroying the hair follicle)80. Results from a meta-analysis and case reports showed that the Nd:YAG laser improved the HS Lesion Area and Severity Index, Physician Global Assessment scores and the number of lesion improvements in people with HS81. Trials with IPL also reported improvement in lesion area, disease severity, and quality of life for people with HS81.

The CO2 laser is commonly used in an ablative mode as part of surgical treatment in HS with the laser targeting water80.

Surgical treatment is an essential intervention, with surgical options ranging from incision and drainage to wide excisions59. Another option, deroofing, can be considered for mild-to-moderate disease and is a tissue-conserving technique that involves removal of the roof of skin tunnel82. This technique can be performed in a procedure room and has been shown to be preferred by patients over surgical and systemic therapies and is well tolerated82.

Future treatments for moderate-to-severe HS

Adalimumab, secukinumab, and bimekizumab are the only biologics approved for hidradenitis suppurativa (HS)68-73. Unravelling the pathogenic pathways involved in the development of HS is paving the way for novel therapeutic targets. Currently, there are various small-molecule drugs and biologics under investigation with the aim of targeting new therapeutic targets in moderate-to-severe HS83.

Dr Joslyn Kirby explains how leveraging the evolving understanding of HS pathophysiology supports the development of novel treatments.

What treatments are currently being investigated for HS?

Treatment targets currently being investigated for HS include tumour necrosis factor (TNF)-α, various interleukins (ILs), leukotriene B4, and the Janus kinase (JAK) pathway (Figure 2)83-85.

Figure 2. Proposed key cells and mediators in the evolution of hidradenitis suppurativa and associated pathogenesis-based target therapies under investigation (Adapted67). IL, interleukin; JAK, Janus kinase; LTB4, leukotriene B4; TNF-α, tumour necrosis factor alpha.

Figure 2. Proposed key cells and mediators in the evolution of hidradenitis suppurativa and associated pathogenesis-based target therapies under investigation (Adapted84). IL, interleukin; JAK, Janus kinase; LTB4, leukotriene B4; TNF-α, tumour necrosis factor alpha.

Are any other TNFα inhibitors being investigated for HS?

Interleukin inhibitors

A number of exploratory phase 2 and phase 3 clinical trials for interleukin inhibitors have been ongoing, with some of the findings recently presented at the European Academy of Dermatology and Venereology (EADV) 2024 congress. These include trials of biologics targeting IL-17A (izokibep, brodalumab) and IL-36 (spesolimab) as well as IL-1α and 1β (lutikizumab). Some key interleukin inhibitors in clinical development for HS are summarised below.

Izokibep

A randomised, placebo-controlled phase 3 study (N=258) investigating the efficacy and safety of izokibep for moderate-to-severe HS has shown promising results86. Recently presented at the EADV 2024 congress, 12-week data demonstrated higher levels of clinical response with izokibep compared with placebo (HiSCR90: 25% vs 9%; HiSCR100: 22% vs 8%). Furthermore, 50% of patients with baseline Hurley stage 2 disease receiving izokibep (n=78) had an abscess and nodule count of less than three by week 12, compared with 27% for the placebo cohort (P<0.01).

Greater improvement in the Dermatology Life Quality Index (DLQI) between baseline and week 12 was achieved in patients receiving izokibep versus placebo (–4.9 vs –2.7; P<0.01). In addition, a higher proportion of patients showed a ≥3-point reduction in skin pain numerical rating scale (NRS) at week 12 with izokibep versus placebo (P<0.01). Overall, izokibep was well tolerated and its safety profile was consistent with other IL-17A-selective inhibitors86.

Brodalumab

Brodalumab is another biologic targeting IL-17A that has been investigated in a number of clinical studies87-89. In one study, 100% of patients (N=10) achieved HiSCR and 80% achieved an International HS Severity Score System (IHS4) category change at week 12. Clear improvements were also demonstrated in pain, itch, quality of life, and depression. No significant adverse events associated with the treatment were reported88.

Spesolimab

In a randomised, double-blind, placebo-controlled, proof-of-clinical-concept trial (N=52), the IL-36 inhibitor spesolimab demonstrated a favourable efficacy and safety profile90. At week 12, the percentage change in total abscess and nodule count was similar between treatment arms; however, spesolimab consistently improved disease severity scores (defined by the Hidradenitis Suppurativa Area and Severity Index, HASI-R) and HiSCR50 compared with placebo. Furthermore, spesolimab showed a favourable safety profile up to week 50 of the open-label extension study (n=45).

Lutikizumab

Lutikizumab is an investigational, dual-variable-domain IL-1α and 1β antagonist91,92. In a randomised, placebo-controlled phase 2 study (N=153), participants with moderate-to-severe HS who did not respond to anti-TNF therapy received lutikizumab weekly or every 2 weeks93. A significantly higher proportion of patients receiving lutikizumab every 2 weeks achieved HiSCR50 at week 16 (59.5%) compared with placebo (35.0%), but this was not reflected in the weekly lutikizumab dosing treatment arm (48.7%)93.

Inhibitors of the Janus kinase (JAK) family

The JAK–STAT pathway can be activated through signalling from various interleukin receptors and type 1 interferons, inducing inflammation94.

Topical ruxolitinib cream, a JAK1/2 inhibitor, has been under investigation in several clinical trials. Data from an open-label extension of a phase 2 study investigating the efficacy and safety of 1.5% ruxolitinib cream for people with mild-to-moderate HS were presented at the EADV 2024 congress95. By week 32 of this study, the abscess and nodule count had decreased by an average of 3.95 in the active treatment arm; patients who were initially assigned to the vehicle control and switched to active treatment at week 16 subsequently attained an average abscess and nodule count reduction of 3.96. Regarding the safety profile of ruxolitinib cream, serious treatment-emergent adverse events occurred in two patients but were not considered related to treatment95.

Other inhibitors of the JAK family include the JAK1 inhibitor povorcitinib (INCB054707), which has been evaluated in three phase 2 trials in people with moderate-to-severe HS83,96,97. The 16-week results of the largest phase 2 study (N=209) showed a greater proportion of patients achieving HiSCR with povorcitinib, compared with placebo, and no evidence for increased risk of serious toxicity97. Phase 3 trials with povorcitinib are ongoing83.

A placebo-controlled, parallel-group phase 2a umbrella trial involving people with moderate-to-severe HS has also evaluated the tyrosine kinase 2 (TYK2) inhibitor ropsacitinib (PF-06826647), the IL-1 receptor-associated kinase 4 (IRAK4) inhibitor zimlovisertib (PF-06650833), and the dual TYK2/JAK1 inhibitor brepocitinib (PF-06700841)83,98. The 16-week results showed consistent and robust efficacy for brepocitinib, but not for zimlovisertib or ropsacitinib98. The authors concluded that broader inhibition of both the TYK2 and JAK1 pathway with brepocitinib may be necessary to demonstrate efficacy in people with moderate-to-severe HS98.

Complement 5a (C5a)

The role of complement in inflammation and its relationships with HS has been well investigated over the past decade99. Specifically, C5a, which links bacterial response pathways to inflammation through upregulation of inflammatory cytokines.

Avacopan, an oral C5a inhibitor, showed preliminary success in improving HiSCR responses compared with placebo (42.6%; 22.4%) when administered at 30 mg twice daily over 16 weeks100. A recombinant anti-C5a antibody, BDB-001, is currently under investigation in two phase 2 multicentre, randomised, double-blind, placebo parallel-controlled trials (N=49 for both trials), assessing its efficacy and safety in adults with moderate-to-severe HS101,102.

Further studies involving larger sampling are required to understand the full potential of C5a antagonism in HS.

Innovations in surgical methods and wound healing

The use of platelet-rich plasma (PRP) therapy is under investigation as part of surgical treatment for HS103. Wound closure during surgery can be problematic, and reconstructive techniques, such as skin flaps and/or grafts, may be required103. The use of PRP injections in reconstructive surgery for HS was shown to improve healing and reduce the number of complications in a retrospective comparative study (N=61)103.

Other surgical methods under investigation include the use of acellular dermal matrix, a biological collagen matrix without immunogenicity, and split-thickness skin grafts103. A retrospective study (N=61) showed co-grafting acellular dermal matrix and split-thickness skin grafts resulted in shorter hospitalisation times and fewer postoperative complications than split-thickness skin grafts alone103.

After surgery, adequate wound dressing with antiseptic function is essential for recovery, though gold-standard management of HS wounds has yet to be identified104. Technologies including silver hydrofiber and polyurethane foam as a secondary dressing, oxygen-enriched oil-based dressings, and ultraportable negative pressure wound therapies are under investigation104.

Trials are ongoing to study the effect of a two-layer biodegradable temporising matrix (with a synthetic dermal replacement and polyurethane foam), a bioelectric dressing containing a polyester matrix with silver and zinc microcell batteries, an ovine forestomach matrix dressing, and a petrolatum dressing with non-stick bandaging in HS105.

To find out more about hidradenitis suppurativa, click here to get expert opinions from Dr Joslyn Kirby

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