HS Treatment

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, 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 isolation^6–8

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, including^10,11:

• 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.

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 monthly^1,12. 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 healthcare professionals¹³. Lack of awareness of HS among healthcare professional is a key factor contributing to delayed and missed diagnoses¹³.

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 published¹⁴. 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 specialists¹⁴.

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 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.

Reducing the symptoms of hidradenitis suppurativa

The aim of treatment is to prevent new lesions and reduce the extent and progression of the disease. This can be achieved with the use of medications, procedures and lifestyle changes¹⁷.

A wide range of medications can be used to reduce flares, manage pain and improve quality of life, including¹⁵:

• 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)

Lifestyles changes, such as smoking cessation and weight loss, can also help to reduce the symptoms of HS¹⁷.

To heal wounds, a mixture of local wound care and oral antibiotics is recommended^5,6. This can include antiseptic washes, negative-pressure wound therapy or antibiotics applied to the skin or wounds^5,6.

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 by^18,19:

• 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 surgery^18,19.

Figure 1. Treatment goals for hidradenitis suppurativa^8,15,20,21

Relieving pain in HS

Pain is a significant factor of HS that reduces QoL²². European and North American guidelines recommend an individualised treatment plan provided by a variety of healthcare professionals, including^5,6:

• Dermatologists
• Pain specialists
• Psychologists

Treatments can include topical analgesics and oral nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, for acute pain as well as opioids and anticonvulsants for chronic pain^8,15.

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 persists²³. 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 options²³.

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 tracts^8,24.

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 utilise the original Hurley staging system combined with evidence-based treatment options^8,26.

A later proposed algorithm is the treatment ladder by Horváth et al., which utilises a refined Hurley staging system that takes into account both the presence and amount of inflammation as a factor for making treatment decisions²⁷.

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 disease^8,15.

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 HS²⁸.

Long-term control of HS requires outcome measures that are simple, quick and validated, in order to define treatment response²⁸

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 practice²⁹.

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 both²⁹.

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 condition³⁰.

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 regime³¹. A cross-sectional survey in an online patient support group revealed that a handbook on HS for patients increased their satisfaction with the treatment process³⁰.

Holistic care in HS

The psychosocial impact of HS is very high and yet is underappreciated by clinicians³². It is therefore important for dermatologists to treat patients from a holistic standpoint that also encompasses emotional symptom management and provides mental health support³³.

All patients should be referred to their local HS Foundation for access to educational materials and local or online patient support groups³². 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 community³².

In addition, screening patients for impacted psychosocial subdomains, including depression, anxiety, body image, sexuality and financial strain, can improve patients’ QoL³². Depending on the subdomain(s) affected, the patient can be referred to a psychiatrist, therapist and/or social worker³².

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 severity^35–38.

Smoking cessation

It is widely known that active smokers have a poorer long-term prognosis than non-smokers or former smokers^35,36. 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 years³⁶.

Weight loss

There is a positive correlation between BMI and disease severity in people with HS³⁸. 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 activity³⁷.

Are there topical treatments for HS?

Topical treatments available for mild inflammatory HS include clindamycin lotion, antiseptic skin cleansers and resorcinol cream¹⁵.

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 clindamycin³⁹. Further studies have also shown that clindamycin can reduce pain after 16 weeks⁴⁰.

However, there is growing evidence that these antibiotic-based treatments may be contributing to antibiotic resistance^41,42. 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 therapy^41,42.

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 HS⁴³. Other topical skin cleansers have not been studied in clinical trials with HS; however, expert opinion supports the use of chlorhexidine and zinc pyrithione^15,44.

Resorcinol cream is recommended as a more targeted approach than clindamycin for long-term HS treatment⁴¹. Resorcinol cream has a keratolytic effect and mild antiseptic properties⁴⁵. 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 days⁴⁶. 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 effects⁴⁷.

What systemic treatments are there for HS?

In patients with inflammation and suppuration, treatment with oral anti-inflammatory antibiotics has been a mainstay²⁵.

Most guidelines recommend a tetracycline antibiotic as first-line therapy for mild-to-moderate disease^25,44,48. 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 properties⁴⁹.

Clindamycin and rifampicin have generally been recommended as first-line treatment for moderate-to-severe HS, or as second-line treatment for mild disease^25,44,48. However, some studies have shown that rifampicin induces enzymatic clearance of clindamycin and clindamycin alone may be as effective as the combination^50–52. Rifampicin monotherapy should be avoided because of implications for tuberculosis treatment and the risk of antibiotic resistance⁵³.

Third-line antibiotic options include dapsone or triple combination therapy with moxifloxacin, metronidazole and rifampicin^25,44,48. Most guidelines suggest oral antibiotic treatment for up to 12 weeks²⁵.

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 intervention^25,44.

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 periods⁴⁵.

Currently, adalimumab and secukinumab are the only biologics approved for the treatment of HS^54–57

Adalimumab, a tumour necrosis factor alpha (TNF-α) inhibitor, was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2015 for the treatment of HS in people aged 12 years and older^56,57. 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 adalimumab⁵⁶.

Secukinumab, an IL-17A inhibitor, was approved by the FDA and EMA in 2023 for the treatment of HS in adults^54,55. Similarly to adalimumab, the European indication for secukinumab highlights its use in patients with disease that has not responded to conventional systemic therapy⁵⁴.

Adalimumab

In 2012, a phase 2 parallel, randomised controlled trial 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 40 mg every other week (EOW; 9.6%) or placebo (3.9%)⁵⁸.

The efficacy of the adalimumab 40 mg weekly dose led to two substantial phase 3 trials – PIONEER I and PIONEER II^58,59

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 placebo⁵⁹.

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 allowed⁵⁹. In PIONEER II adalimumab significantly reduced the number of abscesses and inflammatory nodules, while no reduction was observed in the antibiotic-restricted PIONEER I trial⁵⁹.

Studies have also shown that systemic treatment with adalimumab in combination with surgery improves clinical outcomes and quality of life^60,61.

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)⁶². 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 16⁶².

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)⁶²

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 observed⁶².

What non-pharmacological treatments are there for HS?

Various laser and light-based treatments have been investigated for the treatment of HS, including^45,63:

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

Hair-removal therapies, including the Nd:YAG, Alexandrite and diode lasers, and IPL, have proven useful and use selective photothermolysis targeting haemoglobin (resulting in an anti-inflammatory effect) or melanin (destroying the hair follicle)⁶³. 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 HS⁶⁴. Trials with IPL also reported improvement in lesion area, disease severity and quality of life for people with HS⁶⁴.

The CO₂ laser is commonly used in an ablative mode as part of surgical treatment in HS with the laser targeting water⁶³.

Surgical treatment is an essential intervention, with surgical options ranging from incision and drainage to wide excisions⁴⁵. 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 tunnel⁶⁵. 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 tolerated⁶⁵.

What treatments are currently being investigated for HS?

Treatment targets currently being investigated for HS include TNF-α, various interleukins (ILs), leukotriene B4 and the Janus kinase (JAK) pathway (Figure 2)^66,67.

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.

Are any other TNFα inhibitors being investigated for HS?

Infliximab

One prospective, randomised, double blind, placebo-controlled, crossover study of infliximab has been published. In this study (N=33), significantly more patients in the infliximab group reached a 25–50% decrease in the HS severity index (HSSI) than in the placebo group (P<0.001)⁶⁸.

However, patients on the induction schedule of 5 mg/kg for 8 weeks followed by a maintenance regimen every 8 weeks were seen to develop ‘wearing off’ effects approximately 4 weeks following infusion. A 4-week interval may therefore be more effective⁶⁹.

Etanercept

A small, placebo-controlled, randomised control trial (N=20) compared etanercept 50 mg subcutaneously twice weekly with placebo for 12 weeks. Despite double dosing, no difference was found in the Physician’s Global Assessment, Patient’s Global Assessment or Dermatology Life Quality Index (DLQI)⁷⁰.

What interleukin inhibitors are being investigated for HS?

A number of phase 2 and phase 3 clinical trials for other interleukin inhibitors are currently ongoing. These include trials of biologics that target IL-17A, such as bimekizumab and brodalumab, as well as biologics that target IL-23, such as risankizumab and guselkumab^74,75.

Some key interleukin inhibitors in clinical development for HS are summarised below.

Bermekimab

Anti-IL-1 therapy with bermekimab is under evaluation in phase 2 trials for HS⁷¹. In a prospective randomised trial (N=20), 60% of people treated with 7.5 mg/kg bermekimab intravenously every 2 weeks achieved HiSCR compared with 10% in the placebo group by the end of week 12⁷². In an open-label study (N=42), weekly administration of 400 mg bermekimab was effective in achieving HiSCR at week 12 in those who were naive to or whose disease did not respond to anti-TNF therapy⁷³.

Brodalumab

Brodalumab is another biologic targeting IL-17A that has been investigated in a number of clinical studies^74–76. 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 reported⁷⁶.

Bimekizumab

Bimekizumab has similarly attracted attention as a humanised anti-IL-17A and IL-17F monoclonal antibody⁷⁷.

A phase 2 study of bimekizumab (N=79) assessed the percentage of subjects achieving HS Clinical Response (HiSCR) at week 12 compared with placebo. The uniquely designed study also used adalimumab as an active comparator and used the IHS4 as a secondary outcome measure⁷⁸.

At week 12, a higher percentage of people treated with bimekizumab achieved HiSCR75 (46%) compared with placebo (10%) and those treated with adalimumab (35%)⁷⁸.

In terms of severity, mean IHS4 at week 12 for bimekizumab was 16.0 (SD, 18.0) compared with IHS4 of 40.2 (SD, 32.6) with placebo. Serious adverse events were reported in 4% of the bimekizumab group, 10% of the placebo group and 5% of the adalimumab group⁷⁸.

Phase 3 trials of bimekizumab (BE HEARD 1 and 2) for moderate-to-severe HS are also underway⁶⁶. The first analyses of pooled data were announced at EADV 2023 and showed that, at week 16, response rates were higher with bimekizumab compared with placebo (56–58% vs 33%)⁷⁹. These improvements carried through to week 48, with nearly eight in ten patients achieving HiSCR50.

Ustekinumab

Inhibition of cytokines IL-12 and IL- 23 with ustekinumab (45–90 mg) has also been investigated in a small, prospective, open-label trial. Of the 12 patients that completed the study, 35% achieved a reduction in MSS of ≥50% at week 40, and 47% achieved a reduction of 25–50%. Five patients dropped out of the trial due to lack of efficacy, side effects, or psychological problems⁸⁰.

Guselkumab

The IL-23 inhibitor guselkumab has been investigated in a large phase 2 randomised controlled trial with people with moderate-to-severe HS (NOVA)⁸¹. Patients received either subcutaneous (100 to 200 mg) or intravenous (1,200 mg) guselkumab up to 36 weeks every 4 or 8 weeks. At week 16, no statistically significant differences in HiSCR scores were seen for participants receiving subcutaneous or intravenous treatment, or placebo⁸¹.

Dr Joslyn Kirby explains how research is driving development of effective medicines for people with HS.

What other treatments are being investigated?

Various phase 1 and 2 trials are ongoing or have recently completed. These include the investigation of weekly administration of an anticomplement C5a antibody (IFX-1) in an open-label phase 2 study (N=12) as well as hydroxychloroquine 200 mg twice daily for the treatment of HS^82,83.

Apremilast (PDE-4 inhibitor)

Apremilast (30 mg twice daily), a phosphodiesterase 4 (PDE-4), has been investigated in a randomised control trial (N=20) in people with mild-to-moderate HS. Randomised 3:1 to apremilast and placebo, respectively, 53.3% of the apremilast group achieved HiSCR after 16 weeks compared with 0% of the placebo group (P=0.055). Moreover, a significantly different mean difference in inflammatory nodule count was observed between the two groups (−2.6; P=0.011)⁸⁴.

Complement 5a (C5a)

The role of complement in inflammation and its relationships with HS has been well investigated over the last decade⁸⁵. 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 weeks⁸⁶. Further studies involving larger sampling are required to understand the full potential of C5a antagonism in HS.

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 inflammation⁸⁷.

The JAK1 inhibitor povorcitinib (INCB054707) has been evaluated in three phase 2 trials in people with moderate-to-severe HS^66,88,89. 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 toxicity⁸⁹. Phase 3 trials with povorcitinib are ongoing⁶⁶.

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 PF-06650833 and the dual TYK2/JAK1 inhibitor brepocitinib (PF-06700841)^66,90. The 16-week results, presented at EADV 2022, showed consistent and robust efficacy for brepocitinib, but not for PF‑06650833 or PF‑06826647⁹⁰. 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 HS⁹⁰.

A further IRAK4 inhibitor, KT-474, has been investigated in a phase 1 trial (N=13), and was associated with a reduction in inflammatory biomarkers and an improvement in skin lesions and symptoms⁹¹.

Use of the oral JAK inhibitor tofacitinib has been reported to be effective in a case series of people with HS⁹². It is currently being investigated as part of a phase 2 trial examining the use of tofacitinib in multiple immune skin conditions in people with Down syndrome⁹³.

Topical ruxolitinib cream, a JAK1/2 inhibitor, is also being investigated in two clinical trials⁶⁶. One trial is a phase 2 randomised controlled trial that will assess efficacy and safety, while the other is a phase 2 exploratory trial that will assess efficacy, though both will include participants with Hurley stage 1 and 2^94,95.

Innovations in surgical methods and wound healing

The use of platelet-rich plasma (PRP) therapy is under investigation as part of surgical treatment for HS⁹⁶. Wound closure during surgery can be problematic, and reconstructive techniques, such as skin flaps and/or grafts, may be required⁹⁶. 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)⁹⁶.

Other surgical methods under investigation include the use of acellular dermal matrix, a biological collagen matrix without immunogenicity, and split-thickness skin grafts⁹⁶. A retrospective study (N=61) showed co-grafting acellular dermal matrix and split-thickness skin grafts resulted in shorter hospitalisation times and fewer post-operative complications than split-thickness skin grafts alone⁹⁶.

After surgery, adequate wound dressing with antiseptic function is essential for recovery, though gold-standard management of HS wounds has yet to be identified⁹⁷. Technologies including silver hydrofiber and polyurethane foam as a secondary dressing, oxygen-enriched oil-based dressings, and ultraportable negative pressure wound therapies are under investigation⁹⁷.

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 HS⁹⁸.

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