Study Identifies 3 Hidradenitis Suppurativa Clusters and Evaluates Secukinumab Efficacy

Researchers recently identified 3 hidradenitis suppurativa (HS) clusters among patients involved in the phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) clinical trials. Their findings were published in the Journal of the European Academy of Dermatology and Venereology.¹

These clusters included:

• Predominantly female and with more mild disease.
• Predominantly inclusive of patients from the Asia Pacific, Middle East, and Africa regions and with more moderate disease.
• Patients with high rates of past exposure to biologic therapies, a history of HS-related surgical procedures, and more severe disease.

Image Credit: © DermNet

Background and Methods

The SUNSHINE² and SUNRISE³ trials, both phase 3, double-blind, multicenter studies, evaluated the efficacy of secukinumab in treating moderate to severe HS. Participants were randomly assigned to receive secukinumab every 2 weeks, every 4 weeks, or a placebo for 16 weeks, after which those on placebo were switched to secukinumab. The trials extended treatment up to 52 weeks. Eligible patients were adults with a year-long diagnosis of moderate to severe HS, excluding those with more than 20 draining tunnels at baseline.

Researchers of the present study sought to expand upon previous research presented in the SUNSHINE and SUNRISE trials by characterizing HS patient subtypes. Utilizing a machine learning cluster analysis, they included several baseline characteristics/variables categorized into 1 of 4 groups: patient demographics, disease-specific demographics, presence or lack of comorbidities, and history of prior treatment(s).

The clusters were then evaluated for their treatment responses to treatment with secukinumab (every 2 weeks, every 4 weeks) compared to placebo at week 16. Researchers placed an emphasis on primary and secondary endpoints such as HS clinical response (HiSCR), changes in abscess count, flares, and overall pain reduction (NRS30), while also analyzing outcomes through week 52 of the studies.

Findings

Patients in the trials (n=1084) had an average age of 36.2 years, with a majority being female (56.3%). Most participants were from Europe (61.8%) or the United States (15.2%), and a significant portion were White (78.0%). The majority had Hurley Stage III HS (37.3%) and had undergone extensive prior treatments, including treatment with antibiotics (82.9%) and biologics (23.5%).

Researchers categorized patients into 1 of 3 clusters based on an analysis of baseline characteristics.

• Cluster 1: Comprising 54.1% of patients, this group had a higher proportion of females and reported fewer lesions and better patient-reported outcomes compared to other clusters.
• Cluster 2: Representing 17.8% of participants, this cluster was predominantly younger, male, and from the Asia-Pacific region. They had a greater number of lesions and less exposure to biologics.
• Cluster 3: The largest cluster at 28.1%, showed the most severe disease burden and highest rates of previous biologic treatments and surgeries.

With respect to treatment response, researchers noted that secukinumab significantly improved various HS-associated metrics compared to placebo across all clusters by week 16.

For instance, among members of cluster 1, treatment with secukinumab every 2 weeks or every 4 weeks demonstrated similar effectiveness, significantly outperforming placebo in terms of HS clinical response and reduction in inflammatory nodules and abscesses.

Among individuals in cluster 2, researchers noted improvements achieved with secukinumab, further noting that treatment every 4 weeks exhibited slightly greater efficacy in the reduction of abscess count by week 52.

Cluster 3 also saw benefits from both secukinumab regimens, though treatment every 2 weeks appeared to offer slightly greater benefits in terms of reducing flare-ups and pain scores.

Secukinumab’s efficacy was maintained through the full 52 weeks for all clusters, with improvements sustained across key endpoints. A post hoc analysis revealed no significant differences between treatment regimens (every 2 weeks versus every 4 weeks) or achieving the IHS4-55 response, confirming consistent effectiveness across the dosing schedules.

Conclusions

According to researchers, this clustering analysis represents the largest subtype clustering population in HS yet. Limitations of the analysis may include its use of 1 sole clustering method and inclusion of predominantly White patients.

"Each cluster varied in disease severity and corroborated previous studies with more limited data," according to Passera et al. "Both SECQ2W and SECQ4W regimens are effective across all clusters for improving symptoms of HS, with SECQ2W dosing and longer treatment durations potentially demonstrating greater efficacy in patients with more severe disease."

Moving forward, researchers suggested that additional research of a larger nature be conducted to confirm or expand upon these exploratory findings.

References

1. Passera A, Muscianisi E, Demanse D, et al. New insights on hidradenitis suppurativa phenotypes and treatment response: an exploratory automated analysis of the SUNSHINE and SUNRISE trials. J Eur Acad Dermatol Venereol. August 5, 2024. https://doi.org/10.1111/jdv.20234
2. CAIN457M2301 (SUNSHINE): Secukinumab in hidradenitis suppurativa. NHS Health Research Authority. Accessed August 8, 2024. https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/cain457m2301-sunshine-secukinumab-in-hidradenitis-suppurativa/
3. Study of efficacy and safety of two secukinumab dose regimens in subjects with moderate to severe hidradenitis suppurativa (HS) (SUNRISE). Clinicaltrials.gov identifier: NCT03713632. Updated November 1, 2023. Accessed August 8, 2024. https://clinicaltrials.gov/study/NCT03713632