Tumor Necrosis Factor (TNF)-Alpha Inhibitors in Hidradenitis Suppurativa: A Systematic Review of Inflammatory Markers and Alternative Monitoring Strategies

Hidradenitis suppurativa (HS) is a long-standing inflammatory skin condition with inflammatory nodules, abscesses, and sinus tracts. Tumor necrosis factor-alpha (TNF-alpha) inhibitors like Adalimumab are one of the first-line therapies approved for use in moderate-to-severe HS, but despite that, there is no consensus on what objective biomarkers can be employed to monitor treatment efficacy. This systematic review aims to explain the utility of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as reliable indicators of treatment response to HS. Our objective was to determine if, in patients with HS, treatment with TNF-alpha inhibitors (e.g., adalimumab) leads to a significant change in systemic inflammatory markers like CRP and ESR. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Subsequently, a systematic search was conducted across databases like PubMed/MEDLINE, PMC, ScienceDirect, Cochrane Library, and Clinical Trials, focusing on studies published within the last five years. Search terms included "hidradenitis suppurativa," "adalimumab," and "infliximab." Included studies underwent rigorous quality appraisal with appropriate quality assessment tools, finally resulting in the analysis of only the relevant articles. The evidence confirms that adalimumab therapy leads to a statistically significant reduction in CRP levels, mainly due to its systemic anti-inflammatory effect. However, the clinical value of CRP is questionable, as it is susceptible to confounding by obesity and metabolic syndrome, which are also highly prevalent comorbidities found in HS patients. In contrast, ESR is also proposed as a theoretically superior biomarker, one of the reasons being that it has less interference from these confounders. Our review highlighted a significant lack of prospective data evaluating ESR and CRP changes in response to TNF-alpha inhibitor therapy. A prominent trend was also noticed in recent clinical trials within the past five years to prioritize clinical checkpoints, such as the Hidradenitis Suppurativa Clinical Response (HiSCR), over serological markers. Overall, our systematic review showed that CRP is not a perfect biomarker for monitoring individual treatment response, which is in part due to various confounding factors, such as obesity affecting its level. ESR represents a promising but as yet unvalidated alternative. Currently, the most useful strategy may be a hybrid approach that integrates clinical scores (e.g., HiSCR, International Hidradenitis Suppurativa Severity Score System [IHS4]) with the simultaneous use of inflammatory markers. Our review highlights a critical need for future research to evaluate and compare CRP and ESR to establish their definitive roles in guiding HS therapy.