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Identification of Biomarkers and Critical Evaluation of Biomarker Validation in Hidradenitis SuppurativaA Systematic Review

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the role of biomarkers in hidradenitis suppurativa (HS), and how are they validated?

Findings  In this systematic review, a total of 48 biomarkers were identified with a minimum Grading of Recommendations, Assessment, Development, and Evaluations rating of moderate; only 1 diagnostic (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) achieved a high rating. None of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting; priorities were presented for near-term future research to overcome barriers and limitations of biomarkers in HS.

Meaning  The identification and validation of biomarkers in HS has potential to improve the understanding and management of this chronic, burdensome disease.

Abstract

Importance  The identification and validation of biomarkers in hidradenitis suppurativa (HS) has potential to improve the understanding and management of this chronic, burdensome disease.

Objective  To systematically identify all known HS biomarkers, categorize them by biomarker type, and critically evaluate their validity according to established criteria.

Evidence Review  Eligibility criteria for this review (PROSPERO Registration 230830) included randomized clinical trials, uncontrolled clinical trials, cohort studies, case-control studies, and other observational studies with no restrictions of patient age, sex, race or ethnicity, or language of publication up until December 31, 2020. All articles were categorized into biomarker type, defined using the US Food and Drug Administration Biomarkers, Endpoints, and other Tools (BEST) glossary. Assessment of each identified biomarker was undertaken in line with the US Food and Drug Administration and European Medicines Agency guidelines for the validation of proposed biomarkers. Assessment of the strength of overall data regarding individual biomarkers was undertaken using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.

Findings  A total of 3953 nonduplicate articles were screened, of which 1429 articles were retrieved based on the include/exclusion criteria applied. After full-text screen and data extraction, 106 articles were included in this review. The evidence of strength of 6 categories of biomarkers (susceptibility/risk, diagnostic, monitoring, predictive, prognostic, and pharmacodynamic/response biomarkers) was assessed using GRADE criteria. A total of 48 biomarkers were identified with a minimum GRADE rating of moderate. Only 1 diagnostic (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) achieved a GRADE rating of high. None of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting.

Conclusions and Relevance  Major barriers to the identification, validation, and introduction of routine biomarkers in the management of HS include lack of independent biomarker validation studies (especially assumption-free “omics”-based techniques); insufficient assessment of collinearity between identified or proposed biomarkers; and a lack of routine integration of biomarkers into the structure of clinical trials. International consensus among researchers, clinicians, and pharmaceutical stakeholders is required to standardize goals and methods and encourage biomarker integration into future HS clinical trials. This systematic review presents a number of priorities for near-term future research to overcome such barriers and limitations of biomarkers in HS.

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Article Information

Accepted for Publication: October 7, 2021.

Published Online: January 19, 2022. doi:10.1001/jamadermatol.2021.4926

Correction: This article was corrected on April 13, 2022, to correct the author name “Nisha Chandran Suyien, MD” to “Nisha Suyien Chandran, MD” in the byline.

Corresponding Author: John W. Frew, MBBS, PhD, Department of Dermatology, Liverpool Hospital, Ste 7, Level 1 45-47 Goulburn St, Liverpool, NSW 2170, Sydney, Australia (john.frew@unsw.edu.au).

Author Contributions: Dr Frew had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Der Sarkissian, Lowes, Frew.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Der Sarkissian, Lowes, Mintoff, Frew.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Der Sarkissian, Ring, Frew.

Obtained funding: Frew.

Administrative, technical, or material support: Der Sarkissian, Kirby, Frew.

Supervision: Hessam, Chandran, Frew.

Conflict of Interest Disclosures: Dr Hessam reported serving on advisory boards for AbbVie and participating in trials for AbbVie and Novartis outside the submitted work. Dr Kirby reported receiving personal fees from AbbVie, ChemoCentryx, Incyte, Janssen, Novartis, and UCB Pharma outside the submitted work. Dr Lowes reported serving on advisory boards for AbbVie, InflaRx, Janssen, and Viela Bio; consulting for Almirall, BSN Medical, Incyte, Janssen, Kymera, Phoenicis, and XBiotech; and serving on the medical board of the Hidradenitis Suppurativa Foundation, a voluntary position. Dr Naik reported receiving personal fees (consulting) and grants from AbbVie, personal fees (consulting) from 23andMe and DAVA Oncology, and personal fees (advisory board) from Boehringer Ingelheim; serving as an investigator for Pfizer outside the submitted work; and serving as an unpaid board member of the US Hidradenitis Suppurativa Foundation. Dr Frew reported receiving personal fees from Janssen, Pfizer, Boehringer Ingelheim, AbbVie, Eli Lilly, and LEO Pharma and grants from Sun Pharma outside the submitted work. No other disclosures were reported.

Disclaimer: Dr Naik is an Associate Editor of JAMA Dermatology but was not involved in any of the decisions regarding review of the manuscript or its acceptance.

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