Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial

Vossen, Allard R. J. V.; Doorn, Martijn van; Zee, Hessel H. van der; Prens, Errol P.

doi:10.1016/j.jaad.2018.06.046

Cited by 94 publications

(91 citation statements)

References 24 publications

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“…Evidence is lacking for other biologic therapies, and any clinical decisions should be based on close monitoring and risk: benefit assessments (66). Recent studies showed administration of other biologics such as other TNF-alpha blockers (66, [90][91][92], ustekinumab, (93-96) secukinumab, (97,98) bimekizumab, (99) canakinumab, (3, 100) apremilast, (1,101) anakinra, (102) guselkumab (103,104), and rituximab (105) in management of HS.…”

Section: Administration Of Biologics In Hsmentioning

confidence: 99%

Hidradenitis Suppurativa: Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm

2020

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Hidradenitis suppurativa is one of the most distressing dermatological conditions and has a significant negative impact on patients' quality of life. However, the exact pathogenic mechanisms remain incompletely understood and-therefore-efficient therapies are still lacking. The current manuscript focuses on new findings on its pathogenic mechanisms and aims to provide practical therapy recommendations.

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Section: Administration Of Biologics In Hsmentioning

confidence: 99%

Hidradenitis Suppurativa: Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm

2020

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“…In a comprehensive review of the on-going or completed clinical trials for HS, Maarouf et al [27] identified the following treatment targets-TNFα inhibition, the use of IL-1R antagonists, molecules targeting the IL-17 and IL-12/23 signalling pathways and complementary 5a inhibitors. More recently, the effect of the phosphodiesterase 4 inhibitor Apremilast has been examined in two studies, namely a phase II open label trial [28] and a small randomised placebo controlled trial [29]. Both studies demonstrated a clinical response associated with Apremilast and the treatment was generally well tolerated.…”

Section: Introductionmentioning

confidence: 99%

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel

Langan

Recke

Bokor-Billmann

et al. 2020

IJMS

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The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)-also known as acne inversa-a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.scoring and the HS severity index. Whilst the precise incidence and prevalence of HS is unclear [8], due partly to the diagnostic difficulty associated with HS and the use of both registry data and self-report questionnaires [9]. Garg et al. reported a prevalence of 0.1% in a US-based population analysis, leading the authors to conclude that HS is an uncommon but not rare disease, with over-representation in young, female and African American patients [10]. The current multi-modal treatment approach includes the use of intralesional steroids, surgical and laser therapy, topical and systemic medical antimicrobial therapy and biologic treatments [11].Sartorius scoring and the HS severity index. Whilst the precise incidence and prevalence of HS is unclear [8], due partly to the diagnostic difficulty associated with HS and the use of both registry data and self-report questionnaires [9]. Garg et al. reported a prevalence of 0.1% in a US-based population analysis, leading the authors to conclude that HS is an uncommon but not rare disease, with over-representation in young, female and African American patients [10]. The current multi-modal treatment approach includes the use of intralesional steroids, surgical and laser therapy, topical and systemic medical antimicrobial therapy and biologic treatments [11].

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“…This translational study aimed to identify inflammatory skin markers in response to apremilast 30 mg twice daily for 16 weeks in patients with moderate HS, which showed positive clinical results and have been published previously. 2 However, S100A12 protein levels and IL-17A and IL-17F mRNA expression showed a clear but non-significant decrease in patients receiving apremilast compared with placebo. S100A12 (calgranulin C, EN-RAGE) is a pro-inflammatory, calcium-binding antimicrobial protein that interacts with the receptor for advanced glycation end products (RAGE) and is overexpressed in various inflammatory skin diseases, e.g.…”

Section: Discussionmentioning

confidence: 91%

“…1 Recently, treatment with apremilast for 16 weeks has demonstrated clinically meaningful improvement in moderate HS. 2 In this study (NCT03238469; EudraCT 2016-000859-27), twenty patients with moderate HS (HS-PGA score of 3) were randomized in a 3 : 1 ratio to receive blinded treatment of apremilast 30 mg twice daily or placebo, respectively. Demographic and disease characteristics were similar between treatment arms.…”

Section: Introductionmentioning

confidence: 99%

Apremilast for moderate hidradenitis suppurativa: no significant change in lesional skin inflammatory biomarkers

Vossen

Zee

Davelaar³

et al. 2018

Acad Dermatol Venereol

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Background Treatment with apremilast has recently demonstrated clinically meaningful improvement in moderate hidradenitis suppurativa ( HS ). Objective To evaluate the change in expression of inflammatory markers in lesional skin of HS patients receiving apremilast 30 mg twice daily ( n = 15) for 16 weeks compared with placebo ( n = 5). Methods At baseline, 5‐mm punch biopsies were obtained from an index lesion ( HSL ) and non‐lesional ( HSN ) skin in the same anatomical area. Subsequent HSL samples were taken as close as possible to the previously biopsied site at week 4 and week 16. After sampling, biopsies were split; one half was processed for in vivo mRNA analysis using real‐time quantitative PCR ; the other half was cultured for ex vivo protein analysis using a proximity extension assay (Olink). Linear mixed effects models were calculated to compare the levels of inflammatory markers in HSL skin between apremilast and placebo over time. Results At baseline, 17 proteins with a fold change >2 in HSL vs. HSN skin were identified in 20 patients. The top five were IL ‐17A (5), S100A12, CST 5, IL ‐12/23p40, CD6 (1) with fold changes ranging from 6.6 to 1638, respectively (FDR <0.044). Linear mixed effects models for 75 assays were calculated. Protein levels of S100A12 decreased during treatment in the apremilast group compared with the placebo group ( p = 0.014, FDR = 0.186). None of the 14 genes exhibited significant changes in expression over time. However, an evident downward trend in relative mRNA expression of IL ‐17A and IL ‐17F was demonstrated in patients receiving apremilast. Conclusion We did not detect statistically significant changes in inflammatory markers in HSL skin of HS patients receiving apremilast compared with placebo, despite clinical improvement in the apremilast group. Nonetheless, S100A12 and IL ‐17A were significantly elevated in HSL skin and showed a decrease in response to apremilast. The translational model in clinical trials involving HS clearly needs further improvement.

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Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial

Cited by 94 publications

References 24 publications

Hidradenitis Suppurativa: Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm

Hidradenitis Suppurativa: Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel

Apremilast for moderate hidradenitis suppurativa: no significant change in lesional skin inflammatory biomarkers

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