Investigation Identifies 48 Biomarkers for Hidradenitis Suppurativa

John Frew, MBBS, PhD

A new investigation defined barriers in the identification, validation, and introduction of routine biomarkers in the management of hidradenitis suppurativa (HS).

These barriers included a lack of independent biomarker validation studies, insufficient assessment of collinearity between identified or proposed biomarkers, and a lack of routine integration of biomarkers into the structure of clinical trials.

Investigators led by John Frew, MBBS, PhD, Department of Dermatology at Liverpool Hospital, believed the identification and validation of these biomarkers could potentially improve the understanding and management of the chronic disease.

The team systematically identified all known biomarkers for hidradenitis suppurativa before categorizing them by biomarker type and evaluating their validity through established criteria.

The study was registered with PROSPERO (CRD42021230830) and conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline

The Method

Eligibility criteria consisted of randomized clinical trials, uncontrolled clinical trials, cohort studies, case-control studies, and observational studies with no restrictions of patient age, sex, race or ethnicity, or language of publication until December 31, 2020.

Data collection was performed by 2 of the study authors, and disagreements regarding inclusions to the study were referred to a third author.

Articles were categorized into biomarker type and were defined by the Food and Drug Administration (FDA) BEST glossary. An assessment of each identified biomarker was undertaken in line with the FDA and European Medicines Agency guidelines for validation.

The Findings

Investigators identified a total of 1429 articles using the documented search strategy, along with a total of 11 susceptibility/risk biomarkers, 85 diagnostic biomarkers, 39 monitoring biomarkers, and 20 predictive biomarkers.

After full-text screen and data extraction, 106 articles were included in the review.

The evidence of strength of 6 categories of biomarkers (susceptibility/risk, diagnostic, monitoring, predictive, prognostic, and pharmacodynamic/response biomarkers) was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria.

A total of 48 biomarkers were identified with a minimum GRADE rating of moderate.

Only 1 diagnostic (serum IL-2R), achieved a GRADE rating of high based on multiple independent validation studies, in addition to preanalytical and postanalytical validation.

Diagnostic biomarkers with validation in more than 1 study include tissue interleukin (IL)-17, -IL-1B, serum hepcidin, E-selectin/VEGF/hBD2 combination, YLK-40, serumamyloid A (SAA), C-reactive protein (CRP), S100A7, IL-8,24,27 and IL-6.

Only 1 monitoring biomarker, dermal Doppler vascularity, achieved a GRADE rating of high owing to independent validation and assessment of analytical validity.

Predictive biomarkers fared better, with 2 predictive biomarkers achieving a GRADE rating of high, which were epithelialized tunnels and positive family history of the disease.

However, none of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting.

Despite this, investigators believed their studies in the extant literature was an important step in the development of biomarkers for hidradenitis suppurativa.

They added that the process of validation would require multi-center and independent validation of findings, in addition to assumption-free methods for identifying the most appropriate marker for clinical validation.

“To advance this field in HS and more robustly validate identified biomarkers, stakeholder consensus is required to outline and propose standardized methods for the identification, investigation, and validation of biomarkers in HS,” the team wrote.