Immunomodulatory Drugs in the Treatment of Hidradenitis Suppurativa—Possibilities and Limitations

Świerczewska, Zuzanna; Lewandowski, Miłosz; Surowiecka, Agnieszka; Barańska‐Rybak, Wioletta

doi:10.3390/ijms23179716

Cited by 17 publications

(10 citation statements)

References 80 publications

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“…Emerging targeted therapies for HS focuses much attention on the pathogenesis and most of them are currently under the investigation of phase II clinical trials. Anti-CD40 (iscalimab), anti-Leukotriene A4 (LYS006), CXCR1/2 (LY3041658), anti-IL36 (imsidolimab, spesolimab) and kinase inhibitors (upadacitinib, PF-06650833, brepocitinib, ropsacitinib) are the ones other than the above-mentioned targets which have no outcome of RCTs available so far [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis

2023

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Background: Treatment of hidradenitis suppurativa (HS) is difficult and current guidelines are based mainly on expert opinion and non-randomized controlled trials. Recently, there have been some targeted therapies using uniform primary endpoints for outcome assessment. Objective: Recommendations can be provided on selecting biologics and targeted synthetic small molecules for refractory HS by comparing the efficacy and safety of these medications. Methods: Databases including ClinicalTrial.gov, Cochrane Library, and PubMed were searched. Randomized controlled trials (RCTs) for moderate-to-severe HS were eligible. We performed random-effect network meta-analysis and ranking probability. The primary outcome was Hidradenitis Suppurativa Clinical Response (HiSCR) at 12–16 weeks. Secondary outcome included Dermatology Life Quality Index (DLQI) 0/1, mean change of DLQI from baseline, and adverse effects. Results: A total of 12 RCTs involving 2915 patients were identified. Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w showed superiority to placebo in HiSCR at weeks 12 to 16. In addition, there was no significant difference between bimekizumab and adalimumab as measured by HiSCR (RR = 1.00; 95% CI: 0.66–1.52) and DLQI 0/1 (RR = 2.40, 95% CI: 0.88–6.50). In terms of ranking probability for achieving HiSCR at 12–16 weeks, adalimumab ranked first, followed by bimekizumab, secukinumab 300 mg q4w, and secukinumab 300 mg q2w. All biologics and small molecules did not differ in the development of adverse effects compared to placebo. Conclusions: Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w represent four regimens that produce better outcomes than placebo without increased risk of adverse events. Adalimumab and bimekizumab exhibited best HiSCR and DLQI 0/1 between weeks 12–16.

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Section: Discussionmentioning

confidence: 99%

“…Other potential classes of drugs with high-quality randomized controlled trials (RCTs) were also included in our analysis. This article aimed to provide recommendations on selecting targeted therapies for HS by simultaneously comparing more than two interventions via network meta-analysis (NMA) [ 13 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis

2023

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“…Obesity also results in an abundance of skin folds. The friction at these sites causes cellular damage, which activates an inflammatory response and allows a route of entry for bacteria further contributing to lesion formation in HS [ 17 ].…”

Section: Reviewmentioning

confidence: 99%

The Pathogenesis and Treatment of Hidradenitis Suppurativa

Agnese,

Tariche,

Sharma

et al. 2023

Cureus

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Hidradenitis suppurativa (HS) is a multifactorial disease involving the skin and subcutaneous tissues characterized by deep-seated, painful nodules and abscesses with draining sinus tracts. It affects mostly younger individuals between the ages of 18 and 34. The discomfort and embarrassment that patients affected by HS experience negatively impact their daily lives. It is associated with decreased quality of life and high rates of comorbid depression and anxiety. The rate of depression in HS was reported to be as high as 26%. Its pathogenesis is multifactorial and as such requires a multimodal approach to treatment, which subsequently is reviewed here. Moreover, the pathogenesis of HS is complex and only partially understood. Autoinflammation is the key driver of disease development and is linked with dysregulated inflammasome activation with the subsequent production of inflammatory cytokines. Genetics and cutaneous microbiome play a role in the development of chronic inflammation and lesion formation. Risk factors such as obesity, metabolic syndrome, diabetes, and smoking also add to the systemic inflammation. Targeting these risk factors is a key aspect of the treatment of HS. Lifestyle modifications are used in conjunction with pharmacotherapy and procedures to effectively manage the disease.

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“…Satisfactory, long-lasting results are not currently achieved in most patients treated in this way [6,20]. This makes the search for new treatment concepts imperative [21][22][23][24][25][26]. However, a thorough understanding of HS's pathogenesis is necessary for the development of targeted, highly effective therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

Witte

Schneider‐Burrus

Salinas

et al. 2023

IJMS

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Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4+ memory T (Thmem) cells purified from the blood of patients with HS and matched healthy participants. About 2.0% and 1.9% of protein-coding transcripts were found to be up- and down-regulated in blood HS Thmem cells, respectively. These differentially expressed transcripts (DETs) are known to be involved in nucleoside triphosphate/nucleotide metabolic processes, mitochondrion organization, and oxidative phosphorylation. The detected down-regulation of transcripts involved in oxidative phosphorylation suggest a metabolic shift of HS Thmem cells towards glycolysis. The inclusion of transcriptome data from skin from HS patients and healthy participants in the analyses revealed that in HS skin lesions, the expression pattern of transcripts identified as DETs in blood HS Thmem cells was very similar to the expression pattern of the totality of protein-coding transcripts. Furthermore, there was no significant association between the extent of the expressional changes in the DETs of blood HS Thmem cells and the extent of the expressional changes in these transcripts in HS skin lesions compared to healthy donor skin. Additionally, a gene ontology enrichment analysis did not demonstrate any association of the DETs of blood HS Thmem cells with skin disorders. Instead, there were associations with different neurological diseases, non-alcoholic fatty liver disease, and thermogenesis. The levels of most DETs linked to neurological diseases showed a positive correlation to each other, suggesting common regulatory mechanisms. In summary, the transcriptomic changes in blood Thmem cells observed in patients with manifest cutaneous HS lesions do not appear to be characteristic of the molecular changes in the skin. Instead, they could be useful for studying comorbidities and identifying corresponding blood biomarkers in these patients.

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Immunomodulatory Drugs in the Treatment of Hidradenitis Suppurativa—Possibilities and Limitations

Cited by 17 publications

References 80 publications

Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis

Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis

The Pathogenesis and Treatment of Hidradenitis Suppurativa

Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

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