Biomarkers for HS Face Pervasive Barriers to Routine Clinical Use Despite Potential

Exploring the current role of biomarkers in hidradenitis suppurativa (HS), researchers have found that major barriers in the identification, validation, and introduction of routine biomarkers in the disease state are pervasive.

Findings appeared recently in JAMA Dermatology.

The researchers collected data from over 100 articles of susceptibility/risk, diagnostic, monitoring, and predictive biomarkers, finding that 44 of 155 identified biomarkers were backed by moderate evidence and just 4 were considered to have a high amount of evidence. Even among these 4 biomarkers, said the researchers, none had enough clinical validity to be recommended for routine use in the clinical setting.

“A major limitation to existing biomarker studies is the broad number of studies (including clinical/phenotypic markers, imaging-based markers, proteomics, transcriptomics, and genetic-based markers) with insufficient depth of biomarker validation,” they wrote. “Additionally, given that (to our knowledge) there are no extant longitudinal studies evaluating the risk of developing HS, all susceptibility/risk biomarkers are based on cross-sectional studies of cases and controls.”

From their review, the researchers found that serum biomarkers like serum insulin and demographic factors, such as smoking status and family history, have been associated with HS. They also found serum risk biomarkers that require further validation, and they include serum RBP4, ghrelin, visfatin, TLR10 sequence variants, birthweight, body max index during childhood, and preexisting conditions like type 1 diabetes. The researchers flagged that barriers specific to identifying and validating susceptibility/risk biomarkers relate to delays in HS diagnosis and an inadequate understanding of the pathogenesis of HS.

Based on the review, despite a variety of proposed biomarkers associated with the diagnosis of HS, just 1 diagnostic biomarker was shown to have a strong association with HS based on multiple independent validation measures: serum interleukin (IL)-2 receptor. The researchers note that this probably reflects the systemic nature of inflammation associated with HS.

The researchers found that there was significant overlap between diagnostic and monitoring biomarkers, although they note that none of the proposed biomarkers for monitoring HS have been validated in a longitudinal setting. Dermal doppler vascularity had the highest rate of evidence, and the researchers listed multiple monitoring biomarkers backed by moderate evidence, which included serum IL-17, serum amyloid A, C-reactive protein, IL-8, and sonographic measures like tunnel diameter.

There were 2 predictive biomarkers—presence of epithelialized tunnels and positive family history—that were considered to have strong evidence behind them based on independent validation and integration into 2 phase 3 trials of adalimumab for HS. According to the researchers, this suggests that certain morphological and clinical characteristics may be predictive of response to tumor necrosis factor.

“At present, the main focus of clinical trials is on clinical outcomes, while less emphasis is placed on analysis of serum or tissue-based biomarkers,” wrote the researchers. “Aside from the well-documented issues with outcome measures in HS clinical trials, the consideration of patient stratification by a validated predictive biomarker would aid the identification of more targeted therapeutics for subpopulations of individuals with HS (eg, those with and without epithelialized tunnels) as is done for fistulizing and nonfistulizing Crohn disease in the gastroenterology field.”

Noting collinearity between predictive biomarkers, the researchers suggest examining such collinearity as a first step, as there are suggestions of a relationship between epithelialized tunnels, neutrophil activity, and B cells in HS.

Reference

Der Sarkissian S, Hessam S, Kirby JS, et al. Identification of biomarkers and critical evaluation of biomarker validation in hidradenitis suppurativa: a systemic review. JAMA Dermatol. Published online January 19, 2022. doi:10.1001/jamadermatol.2021.4926