EADV 2024

HS clinical trials

“Perhaps we are seeing the first steps in individualised patient treatment.” Thrasyvoulos Tzellos (Nordland Hospital Trust, Bodø, Norway) discusses what the latest targeted treatments reported at EADV 2024 may signify for people with HS. View transcript.

Clinical trial updates on moderate-to-severe hidradenitis suppurativa (HS) from the European Academy of Dermatology and Venereology (EADV) congress 2024, covering outcome data from the phase 3 SUNSHINE, SUNRISE, and BE HEARD I&II trials, and the phase 2 MIRA trial.

SUNSHINE and SUNRISE phase 3 trials

• SUNSHINE and SUNRISE are identical placebo-controlled, double-blind phase 3 trials
• Patients with moderate-to-severe HS were randomised to secukinumab 300 mg every 2 weeks or 4 weeks, or placebo between weeks 0 and 16
• Patients on placebo were switched to secukinumab at week 16; patients on secukinumab stayed on the same treatment from weeks 16 to 52
• In published data, the proportion of patients with an HS clinical response (primary outcome) at week 16 was met for secukinumab every 2 weeks compared with placebo; the most common adverse event (AE) up to week 16 was headache¹

At EADV 2024, pooled data from SUNSHINE and SUNRISE were presented on cardiovascular risk (Falk Bechara, Ruhr-University Bochum, Germany), psychiatric comorbidities (Jacek Szepietowski, Wroclaw Medical University, Poland), and the impact of lesion type on clinical response (Hessel van der Zee, Erasmus MC University, Rotterdam, the Netherlands).

Cardiovascular risk

Patients with HS are at risk of cardiovascular (CV) events, and have an increased risk of all-cause and CV-related mortality.² At EADV, Bechara reported that treatment with secukinumab in patients with HS showed a nonsignificant reduction in systemic inflammation from baseline to week 52, measured by C-reactive protein.

In both secukinumab treatment groups, there were no clinically meaningful changes in total cholesterol, low-density lipoprotein cholesterol, triglycerides, body mass index, blood pressure, or glycated haemoglobin versus the placebo group at week 16, which was sustained to week 52.

Psychiatric comorbidities

Patients with HS have approximately a twofold higher risk of having clinical depression and anxiety disorders compared with those without HS³

At EADV, Szepietowski showed that treatment with secukinumab compared with placebo improved anxiety and depression from weeks 16 to 52; there was also a low incidence of psychiatric AEs. The most frequently reported AEs through week 52 were depression (2.8% for secukinumab every 2 weeks; 1.9% for secukinumab every 4 weeks) and anxiety (0.3% for secukinumab every 2 weeks , 1.1% for secukinumab every 4 weeks).

The impact of lesion type

Given the diverse clinical presentations of HS, it is relevant to know the effect of lesion type and lesion number on treatment for HS.⁴ Van der Zee showed pooled data from a post hoc analysis to evaluate the effect of lesion type, and count at baseline, on treatment response.

At weeks 16 and 52, there was a trend for increased HS clinical response (HiSCR) rates for patients with no draining tunnels relative to those with draining tunnels observed at baseline. There was no trend for response status in the abscess and nodule count subgroups at weeks 16 and 52 versus baseline.

Tzellos highlights the latest findings in the management of HS, including combatting moisture-associated skin damage and factors related to malignancy risk in severe HS. View transcript.

BE HEARD I&II phase 3 trials

• BE HEARD I&II are identical placebo-controlled phase 3 trials
• Patients were randomised to receive bimekizumab 320 mg on one of three dosing schedules, or placebo for 16 weeks followed by bimekizumab every 2 weeks to week 48
• In published data, the primary outcome (HiSCR ≥50%) at week 16 was met for bimekizumab every 2 weeks versus placebo
• The most frequently reported AE to week 48 was hidradenitis⁵

At EADV 2024, Christos Zouboulis (Brandenburg Medical School, Dessau, Germany) presented efficacy and safety data from BE HEARD I&II and the BE HEARD extension study, Jacek Szepietowski presented on the effect of bimekizumab on patient-reported outcomes (PRO), and John Ingram (Cardiff University, UK) reported on the periodic worsening of HS symptoms (‘flares’).

BE HEARD extension study

Zouboulis showed clinically meaningful improvements in HiSCR at week 96 for patients with moderate-to-severe HS on bimekizumab, compared with rates at weeks 16 and 48, with rates of 85.4% for HiSCR 75, 77.1% for 57.6% for HiSCR 90, and 44.2% for HiSCR 100. Bimekizumab was generally well tolerated; no new safety signals were observed. Safety over 2 years was consistent with BE HEARD I&II and studies of bimekizumab in other indications.^5-8

Patient-reported outcomes

In patients who switched from placebo to bimekizumab at week 16, HS Symptom Questionnaire (HSSQ) item scores were substantially reduced from weeks 16 to 48; further improvements were observed for those continually treated with bimekizumab. Between weeks 16 and 48, continual treatment with bimekizumab increased the proportion of patients achieving a minimally clinical important difference (MCID) in Dermatology Life Quality Index (DLQI); patients who switched from placebo to bimekizumab at week 16 attained similar proportions at week 48.

Patient advocate Cindy Stillman (USA) and Steve Daveluy (Wayne State University, Detroit, Michigan, USA) discuss how healthcare providers can best support patients with HS in dealing with its social consequences and disease-related pain. View transcript.

Impact on periodic worsening of symptoms

Ingram noted that fewer patients treated with bimekizumab had periodic worsening of symptoms to week 16 compared with placebo. After switching from placebo to bimekizumab, the proportion of patients who had an HS flare reduced rapidly, with results comparable to patients on continuous bimekizumab from baseline. Approximately 80% of patients continuously treated with bimekizumab from baseline were flare-free at week 48.

MIRA phase 2 trial

• Sonelokimab is a novel humanised nanobody for inhibiting interleukin (IL)-17A and IL-17F and penetrating difficult-to-reach sites of inflammation
• MIRA is a 24-week, randomised, double-blind, placebo-controlled phase 2 trial
• Published data shows that more patients on sonelokimab achieved the HS clinical response score versus placebo (14.7%) at week 12 (primary endpoint)
• There were no unexpected safety findings for sonelokimab⁹

Alexa Kimball (Harvard Medical School and Beth Israel Deaconess Medical Center) reported on inflammatory lesion resolution and Martina Porter (Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) presented week 24 data from MIRA on PROs.

Inflammatory lesion resolution

Kimball noted that most patients with moderate-to-severe HS on sonelokimab 120 mg achieved complete resolution of abscesses (68.2%); 49.0% had complete resolution of draining tunnels, 31.0% had complete resolution of abscesses and/or inflammatory nodules, and 24.1% achieved complete inflammatory remission. Similar improvements were evident for sonelokimab 240 mg.

Patient-reported outcomes

At week 24, more than 60% of patients on sonelokimab achieved DLQI MCID (120 mg, 61.5%; 240 mg, 68.6%). The Hidradenitis Suppurativa Quality of Life (HiSQoL) total score improved to week 24 (mean change from baseline: 120 mg, –11.4 points; 240 mg, –10.4 points). In the symptom HiSQoL subscale at week 24, 45.7% of patients taking sonelokimab 120 mg, and 50.0% of those taking sonelokimab 240 mg, achieved the Numeric Rating Scale (NRS) 30, indicating improved skin pain response.

References

1. Kimball, 2023. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): Week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials. https://www.doi.org/10.1016/s0140-6736(23)00022-3
2. Reddy, 2020. Incidence of myocardial infarction and cerebrovascular accident in patients with hidradenitis suppurativa. https://www.doi.org/10.1001/jamadermatol.2019.3412
3. Phan, 2020. Hidradenitis suppurativa and psychiatric comorbidities, suicides and substance abuse: Systematic review and meta-analysis. https://www.doi.org/10.21037/atm-20-1028
4. Frew, 2020. Clinical response rates, placebo response rates, and significantly associated covariates are dependent on choice of outcome measure in hidradenitis suppurativa: A post hoc analysis of PIONEER 1 and 2 individual patient data. https://www.doi.org/10.1016/j.jaad.2019.12.044
5. Kimball, 2024. Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): Two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials. https://www.doi.org/10.1016/s0140-6736(24)00101-6
6. Reich, 2021. Bimekizumab versus secukinumab in plaque psoriasis. https://www.doi.org/10.1056/nejmoa2102383
7. Merola, 2023. Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: A randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE). https://www.doi.org/10.1016/s0140-6736(22)02303-0
8. van Der Heijde, 2023. Efficacy and safety of bimekizumab in axial spondyloarthritis: Results of two parallel phase 3 randomised controlled trials. https://www.doi.org/10.1136/ard-2022-223595
9. NCT05322473, 2024. Evaluation of sonelokimab for the treatment of patients with active moderate to severe hidradenitis suppurativa. https://clinicaltrials.gov/ct2/show/NCT05322473

Advances in HS diagnosis

What was the latest on HS diagnosis presented at EADV 2024? Thrasyvoulos Tzellos (Nordland Hospital Trust, Bodø, Norway) discusses data on tools to aid diagnosis and factors contributing to diagnostic delay. View transcript.

Early diagnosis and treatment of hidradenitis suppurativa (HS) is crucial to reducing disease progression and symptom management.¹ At EADV 2024:

• Alexander Katoulis (“Attikon” General University Hospital, Athens, Greece) presented registry data on trends in HS diagnosis delay
• Elizabeth Nash (Adelphi Real World, Bollington, UK) contributed first-person data on HS diagnosis from clinician and patient perspectives
• John Ingram (Cardiff University, UK) showed interim results from the HELyx implementation study in Germany
• Richard Marie-Aleth (Timone Hospitals, Marseille, France) presented on diagnostic wandering from the French VHS project

A registry study of HS diagnosis delay

A retrospective registry-based study, conducted between 2015 and 2024, evaluated the medical records of 206 patients with HS, who attended the HS Clinic at “Attikon” General University Hospital in Athens, Greece.

Katoulis observed that the mean diagnostic delay for HS, measured between 2015 and 2024, was 9.3 years

There was a positive trend towards earlier diagnosis, which stalled in 2020–2021, possibly due to COVID-19. Continuing education on HS and strategic public health messaging are needed to sustain and enhance early HS diagnosis.

Diagnosis of HS from the patient’s perspective

First-person data are lacking on HS diagnosis from clinician and patient perspectives.^2,3 In this study, survey data from dermatologists (USA, n=81; Europe, n=181) and their HS patients (USA, n=188; Europe, n=377) in the USA, France, Germany, Italy, and Spain, from 2020 to 2021, was taken from the Adelphi Real World HS Disease Specific Programme™.

Presented at EADV by Nash, the overall highest rated dermatologist-reported challenges for diagnosing HS were:

• “HS signs have similarities with other conditions” (29%)
• “Low awareness of HS” (24%)
• “Lack of education available for identifying and diagnosing HS” (20%)

A lower proportion of European clinicians believed that “increased awareness/education of patients” could benefit early diagnosis of HS compared with US dermatologists (27% vs 69%; P<0.001). Conversely, “increased awareness/education of physicians” was noted by more European clinicians (88% vs 72%; P=0.001). Clinicians reported that “disease information availability” (42%) and “availability of diagnostic tests” (34%) could expedite early HS diagnosis.

US patients experienced longer delays than European patients to initial clinical consultation about symptoms (1.8 years vs 1.2 years; P=0.044). Time from initial consultation to diagnosis of HS was 1.8 years for US patients and 1.5 years for European patients (P=0.49). Of all patients, 40% reported a delay in being seen and treated by a HS specialist following HS diagnosis, which was reported in more US than European patients (46% vs 37%; P=0.043).

Of all patients, 54% agreed with the statement “I feel that more needs to be done to speed up diagnosis of HS.” Overall, 91% of all patients agreed that “I knew nothing about HS before I was diagnosed with the condition.”

Overall, 46% of patients had been misdiagnosed prior to HS diagnosis, most commonly as boils (45%), acne (33%), or furunculosis (23%)

Steve Daveluy (Wayne State University, Detroit, Michigan, USA) and patient with HS Cindy Stillman discuss the different forms that multidisciplinary care can take for HS and the challenges faced by clinicians caring for people with HS. View transcipt.

Improving screening and diagnosis of HS: HELyx

HELyx is an ongoing, effectiveness-implementation German study that evaluates an online training strategy (HS care package) for HS diagnosis and management.

In total, 187 clinicians completed the baseline survey (86 dermatologists; 101 non-dermatologists), and 124 clinicians (56 dermatologists, 68 non-dermatologists) completed the week 12 survey. A higher proportion of clinicians had consulted with at least one patient with suspected or diagnosed HS by week 12 (96.8%) than during the 12 weeks prior to baseline (91.4%). Dermatologists and non-dermatologists who used an HS diagnostic screening tool mainly sought information on lesion location, followed by descriptions or images of nodules, abscesses, or draining tunnels.

At week 12, 55.8% of clinicians who saw at least one patient with suspected or diagnosed HS had used the diagnostic screening tool developed by HELyx; non-dermatologists showed a higher use of the HELyx tool than dermatologists (66.7% vs 42.6%).

Greater use of HS diagnostic screening tools by non-dermatologists following implementation of the HELyx care package highlights that HS-specific tools are needed for clinicians without specialist training in dermatology

Risk factors for diagnostic wandering: The VHS project

Patients with HS report enduring several years of uncertainty before being diagnosed with HS. This prolonged period of medical ambiguity – “wandering diagnosis” – can worsen symptoms and adversely affect patient wellbeing.¹

Marie-Aleth presented results from the French VHS project (N=1,055) on risk factors for diagnostic wandering:

• Income below the median (OR, 1.65; 95% CI, 1.17–2.32; P=0.004)
• Having had HS for 3 years or more (OR, 1.71; 95% CI, 1.1–2.1; P=0.01)
• Being a woman (OR, 1.97; 95% CI; 1.36–2.86; P=0.0004)
• Lack of a higher-education degree (OR=2.07; 95% CI, 1.12–3.82; P=0.01)

More women than men had diagnostic wandering for HS (72.15% [n=583] for women, 57.89% [n=143] for men; P<0.001). There was no significant association between living in an urban or rural area and diagnostic wandering.

References

1. Nguyen, 2021. Hidradenitis suppurativa: An update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life. https://www.doi.org/10.1111/jdv.16677
2. Esmann, 2011. Psychosocial impact of hidradenitis suppurativa: A qualitative study. https://www.doi.org/10.2340/00015555-1082
3. Marzano, 2024. Improving hidradenitis suppurativa management: Consensus statements from physicians and patients’ perspectives. https://www.doi.org/10.1007/s00403-024-03316-2

New targets and emerging treatments for HS

"Hidradenitis suppurativa is a disease which has, like atopic dermatitis, an exciting pipeline." Thrasyvoulos Tzellos (Nordland Hospital Trust, Bodø, Norway) explains how investigational targeted treatments for HS could help to address unmet needs. View transcript.

Promising treatments for hidradenitis suppurativa (HS) are under investigation in trials that target key inflammatory mediators of HS, such as interleukin (IL)-17, IL-36, IL-1α/1β, or Janus kinase (JAK). Martina Porter (Harvard Medical School, Boston, Massachusetts, USA), Kim Papp (University of Toronto, Ontario, Canada), Kristian Reich (University Medical Center Hamburg-Eppendorf, Germany), and Robert Hunger (University of Bern, Switzerland) presented at EADV 2024 on new targets and treatments for HS.

Targeting IL-17A dysfunction

Papp presented 12-week data from a randomised, placebo-controlled phase 3 study on the efficacy and safety of izokibep for moderate-to-severe HS. Izokibep is designed to selectively inhibit IL-17A, which plays a role in the inflammatory process in HS.

The primary endpoint of the trial was HS clinical reponse (HiSCR 75) to week 12 for izokibep 160 mg (n=129) once weekly compared with placebo once weekly (n=129).

Izokibep showed separation from placebo at week 4 (P<0.05); by week 12, 33% of patients on izokibep achieved HiSCR 75, compared with 21% of those taking placebo (P<0.05)

Higher levels of clinical response, defined as HiSCR 90/100, were demonstrated with izokibep: around one in four patients taking izokibep achieved these targets, compared with about one in nine of those taking placebo. Consistent with these data, 50% of patients with baseline Hurley stage 2 disease for izokibep (n=78) had an abscess and nodule (AN) count of less than three by week 12, compared with 27% for placebo (P<0.01).

Patients with HS on izokibep achieved greater improvement in the Dermatology Life Quality Index (DLQI) between baseline and week 12 versus placebo (–4.9 vs –2.7; P<0.01), and a higher proportion showed a ≥3-point reduction in skin pain numerical rating scale (NRS) at week 12 with izokibep versus placebo (P<0.01).

Vasculitis was the only observed serious treatment-emergent adverse event (TEAE) for izokibep, and 65.1% of the izokibep group versus 7.8% of the placebo group reported injection-site reactions. Izokibep was overall well tolerated, with a safety profile consistent with other IL-17A-selective inhibitors.

Emerging treatments for HS in clinical trials

Ruxolitinib cream for mild disease

Porter presented data from the open-label extension of a phase 2 study of ruxolitinib 1.5% cream – a selective Janus kinase 1/2 inhibitor – for mild-to-moderate HS. The participants had Hurley stage I or II HS and no draining tunnels.

By the end of the full 32-week period, the AN count in patients initially assigned to active treatment had decreased by an average of 3.95. Patients who initially used the vehicle control but switched to active treatment at week 16 “essentially caught up,” to attain an average AN count of 3.96.

There were two TEAEs considered related to treatment during the open-label period. These were diarrhoea and application site pain and were both grade 1. Serious TEAEs occurred in two patients but were not considered related to treatment.

"Through evidence-based analysis and consensus, adalimumab, bimekizumab, and secukinumab should be first-line treatment for HS after failure of one round of antibiotic use." Tzellos reviews the forthcoming European guidelines for HS. View transcript.

Other phase 2 findings

Hunger presented data on several potential treatments for more severe disease.

Spesolimab

Spesolimab, which inhibits IL-36 signalling, was investigated for HS in a randomised double-blind placebo-controlled proof-of-clinical-concept trial.¹ The percentage change from baseline in total AN count was similar between spesolimab and placebo at week 12; however, spesolimab consistently improved overall disease severity, with a beneficial effect on draining tunnels versus placebo (–40.1% vs +56.6%), including the proportion of patients achieving a draining tunnel count of 0 (25.0% vs 6.7%).

Spesolimab tended to improve patient-reported pain, and it showed a favourable safety profile up to week 50 of the open-label extension study, which involved 45 patients, including those originally in the placebo group.

“It takes a long time to get an appropriate diagnosis. I saw four different dermatologists over 15–20 years before I was diagnosed with HS.” Patient advocate Cindy Stillman (USA) and dermatologist Steve Daveluy (Wayne State University, Detroit, Michigan, USA) discuss the lived experience of HS and consider the advantages of conference attendance. View transcript.

Lutikizumab

Lutikizumab is an investigational, dual-variable-domain antagonist of IL-1α and 1β, which are elevated in HS lesions.² Hunger described a 16-week, phase 2, randomized, placebo-controlled trial that evaluated the safety and efficacy of lutikizumab 300 mg in 153 adult patients with moderate-to-severe HS who had not responded to anti-tumour necrosis factor therapy. Most patients had severe baseline Hurley stage 3 disease characterised by scarring, lesions, and sinus tracts. The difference in the proportion of patients who achieved HiSCR 50 at week 16 was statistically significant compared with placebo (35.0%) for patients who received lutikizumab 300 mg every other week (59.5%), but not for those who received 300 mg weekly dosing (48.7%). Hunger noted that lutikizumab could be an option for patients with HS who are not responsive to adalimumab.

Remibrutinib

Remibrutinib is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK). Plasma cells dominate the leukocyte population in HS lesions, and BTK decreases the proliferation of these plasma cells. A randomised phase 2 trial found that 72.7% of patients treated with remibrutinib 25 mg twice-daily achieved the simplified HiSCR 50 response at week 16, compared with 48.5% of those in the 100 mg cohort, and 34.7% for placebo.

Hunger observed that the lack of validated biomarkers makes treatment selection for HS a matter of trial and error

References

1. Alavi, 2024. Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: A randomized double-blind placebo-controlled clinical trial. https://www.doi.org/10.1093/bjd/ljae144
2. Van Der Zee, 2011. Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: A rationale for targeting TNF-α and IL-1β. https://www.doi.org/10.1111/j.1365-2133.2011.10254.x