Development and validation of <scp>IHS4</scp>‐55, an <scp>IHS4</scp> dichotomous outcome to assess treatment effect for hidradenitis suppurativa

Tzellos, Thrasyvoulos; Straalen, Kelsey R. van; Kyrgidis, Athanassios; Alavi, Afsáneh; Goldfarb, Noah; Gulliver, Wayne; Jemec, Gregor B E; Lowes, Michelle A.; Marzano, Angelo Valerio; Prens, Errol P.; Sayed, Christopher; Zee, Hessel H van der; Zouboulis, Christos C.

doi:10.1111/jdv.18632

Cited by 30 publications

(45 citation statements)

References 11 publications

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“…Therefore, attention is currently being devoted to improving outcome measures [ 11 , 12 ] and developing human HS models [ 13 , 14 ]. Such models contain ex vivo systems such as the 3D-SeboSkin model [ 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

HS 3D-SeboSkin Model Enables the Preclinical Exploration of Therapeutic Candidates for Hidradenitis Suppurativa/Acne Inversa

et al. 2023

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Despite the rapid development in hidradenitis suppurativa (HS) research, the immediate introduction of potent therapeutic compounds in clinical trials and the lack of definitive outcome measures have led to the discontinuation of potential therapeutic compound studies. HS is a solely human disease, and therefore, the search for preclinical human models has been given priority. The 3D-SeboSkin model, a co-culture of human skin explants with human SZ95 sebocytes as a feeder layer, has been shown to prevent the rapid degeneration of human skin in culture and has been validated for HS preclinical studies. In this work, the HS 3D-SeboSkin model has been employed to characterize cellular and molecular effects of the EMA- and FDA-approved biologic adalimumab. Adalimumab, a tumor necrosis factor-α inhibitor, was shown to target inflammatory cells present in HS lesions, inducing a prominent anti-inflammatory response and contributing to tissue regeneration through a wound healing mechanism. Adalimumab inhibited the lesional tissue expression of TNF-α, IL-3, IL-15, and MCP-3 and downregulated the secretion of IL-1α, IL-5, RANTES, MCP-2, TNF-α, TNF-β, TGF-β, and IFN-γ. In contrast, IL-6 was stimulated. The compound failed to modify abnormal epithelial cell differentiation present in the HS lesions. Patients with Hurley stage II lesions exhibited stronger expression of autophagy proteins in perilesional than in lesional skin. Adalimumab modified the levels of the pro-apoptotic proteins LC3A, LC3B, and p62 in an individual, patient-dependent manner. Finally, adalimumab did not modify the NFκB signal proteins in SZ95 sebocytes and NHK-19 keratinocytes, used to study this specific pathway. The administration of the validated HS 3D-SeboSkin model in ex vivo studies prior to clinical trials could elucidate the individual pathogenetic targets of therapeutic candidates and, therefore, increase the success rates of clinical studies, minimizing HS drug development costs.

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Section: Introductionmentioning

confidence: 99%

HS 3D-SeboSkin Model Enables the Preclinical Exploration of Therapeutic Candidates for Hidradenitis Suppurativa/Acne Inversa

et al. 2023

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“…It was calculated using the following formula: (number of nodules × 1) + (number of abscesses × 2) + (number of fistulas × 4) [ 12 ]. The reduction of 55% in the IHS4 score was also collected (IHS4-55) [ 13 ]. The Hurley classification was used to assess structural damage.…”

Section: Methodsmentioning

confidence: 99%

“…(number of fistulas 9 4) [12]. The reduction of 55% in the IHS4 score was also collected (IHS4-55) [13].…”

Section: Main Variablesmentioning

confidence: 99%

Potential Predictors of Cardiovascular Risk Improvement in Patients with Hidradenitis Suppurativa Treated with Adalimumab: A Pivotal Study of Factors Associated with Carotid Intima–Media Thickness Reduction

Sánchez‐Díaz

Salvador‐Rodríguez

Cuenca‐Barrales

et al. 2023

Dermatol Ther (Heidelb)

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Introduction: Hidradenitis suppurativa (HS) has been linked to higher cardiovascular risk (CVR) due to its inflammatory burden. There is little evidence on how biologic treatment could modify the cardiovascular risk of patients with HS. The aims of the present study were to explore the modification of CVR in patients under adalimumab treatment and to explore the potential factors associated with CVR improvement. Methods: A prospective longitudinal study was performed. A cohort of patients with HS treated with adalimumab was followed up. Carotid intima-media thickness (IMT) and other clinical and biochemical CVR factors were collected at baseline and 32 weeks after starting the treatment.Results: Twenty-seven patients with severe HS were included. Overall, there were no differences in IMT between baseline (633 lm) and 32 weeks follow-up (634 lm). However, 40.7% (11/27) of the patients presented an improvement in IMT. This group (IMT responders) had a higher prevalence of dyslipidemia, diabetes mellitus, higher HbA1c levels, consumed more tobacco, and had higher BMI at baseline. Moreover, these patients had lower IHS4 scores at baseline and tended to have a greater IMT basal value, indicating a higher burden of subclinical atherosclerosis. Conclusions: Adalimumab treatment might benefit a subset of patients with HS in terms of cardiovascular risk reduction. In light of the results of the present study patients with classical cardiovascular risk factors, and those with higher burden of subclinical atherosclerosis and with less inflammatory load, may be more likely to improve their IMT during adalimumab treatment.

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“…draining tunnels × 4) as the threshold for responsiveness—have been suggested as feasible validated instruments to assess therapeutic responsiveness. However, because both still require lesion identification and quantification, some of the same issues of reliability and reproducibility exist with these instruments . The Hidradenitis Area and Severity Index Revised (HASI-R), which incorporates signs of disease activity and body surface area without the need for lesion counts, is a reliable and valid instrument for measuring HS disease severity .…”

Section: The Current Landscape Of Hs Disease Activity Measuresmentioning

confidence: 99%

The Critical Need for Reliable and Clinically Meaningful Outcome Measures for Hidradenitis Suppurativa

Naik

2023

JAMA Dermatol

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Development and validation of IHS4‐55, an IHS4 dichotomous outcome to assess treatment effect for hidradenitis suppurativa

Cited by 30 publications

References 11 publications

HS 3D-SeboSkin Model Enables the Preclinical Exploration of Therapeutic Candidates for Hidradenitis Suppurativa/Acne Inversa

HS 3D-SeboSkin Model Enables the Preclinical Exploration of Therapeutic Candidates for Hidradenitis Suppurativa/Acne Inversa

Potential Predictors of Cardiovascular Risk Improvement in Patients with Hidradenitis Suppurativa Treated with Adalimumab: A Pivotal Study of Factors Associated with Carotid Intima–Media Thickness Reduction

The Critical Need for Reliable and Clinically Meaningful Outcome Measures for Hidradenitis Suppurativa

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