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Dermatologic Therapy Sep 2022Hidradenitis suppurativa (HS) is a chronic inflammatory often recalcitrant to treatment. There is a lack of an updated systematic data review for infliximab use in HS.... (Meta-Analysis)
Meta-Analysis Review
Hidradenitis suppurativa (HS) is a chronic inflammatory often recalcitrant to treatment. There is a lack of an updated systematic data review for infliximab use in HS. We conducted a systematic review and meta-analysis of literature on infliximab in HS. This study was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was pre-registered on PROSPERO (CRD42021283596). In 9/2021, MEDLINE and EMBASE were systematically searched for articles on infliximab in HS. Non-English, duplicate, and studies with <5 HS patients were excluded. Study quality was assessed utilizing Cochrane Risk of Bias for prospective trials and Newcastle-Ottawa Scale for cohort studies. Random effects meta-analytical model, Cochran's Q statistic, and I squared index were performed. Nineteen articles (314 patients) met inclusion criteria (six prospective, 13 retrospective studies). All patients with HS severity data available (n = 299) had moderate-to-severe disease. Outcome measures used for meta-analysis of the pooled response rate were largely based on clinician reported outcomes (16 studies). One utilized both clinician and patient assessment. Two utilized patient-reported response alone. The pooled response rate of HS patients to infliximab was 83% (95% CI, 0.71-0.91). The most common adverse events (AEs) included non-serious infections (13.2%) and infusion reaction (2.9%). The rate of serious AEs was 2.9%. Study limitations include the small number of prospective studies and heterogeneity between studies. Overall, infliximab is an effective treatment for moderate-to-severe HS. Efficacy of infliximab in HS should be compared to other biologics in larger, randomized controlled trials.
Topics: Antibodies, Monoclonal; Hidradenitis Suppurativa; Humans; Infliximab; Prospective Studies; Retrospective Studies
PubMed: 35790062
DOI: 10.1111/dth.15691 -
Dermatology (Basel, Switzerland) 2021Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis that imparts a significant burden on patients and presents a management challenge for healthcare... (Comparative Study)
Comparative Study Review
Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis that imparts a significant burden on patients and presents a management challenge for healthcare providers. As attention to this debilitating condition has grown over recent years, our understanding of HS pathogenesis and optimal treatment approaches continues to evolve. Nine HS treatment guidelines developed by various expert organizations have been published, encompassing therapeutic modalities ranging from topical agents to systemic therapies to procedural interventions. These guidelines demonstrate significant overlap in treatment recommendations and have all been published within the last 5 years. Therefore, we aim to compare and synthesize the recommendations of international HS treatment guidelines and to encourage inter-organizational communication for the development of consensus or staggered publication of recommendations for HS management.
Topics: Consensus; Hidradenitis Suppurativa; Humans; Practice Guidelines as Topic
PubMed: 31645040
DOI: 10.1159/000503605 -
JCI Insight Oct 2020Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in...
Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.
Topics: Biomarkers; Case-Control Studies; Gene Expression Regulation; Gene Regulatory Networks; Hidradenitis Suppurativa; Humans; Signal Transduction; Single-Cell Analysis; T-Lymphocytes, Regulatory; Transcriptome; Tumor Necrosis Factor-alpha
PubMed: 32841223
DOI: 10.1172/jci.insight.139932 -
Clinical and Experimental Immunology Aug 2020The skin is one of the most important organs in the body, providing integrity and acting as a barrier to exclude microbes, allergens and chemicals. However, chronic skin... (Review)
Review
The skin is one of the most important organs in the body, providing integrity and acting as a barrier to exclude microbes, allergens and chemicals. However, chronic skin inflammation can result when barrier function is defective and immune responses are dysregulated or misdirected against harmless or self-antigens. During the last 15 years interleukin (IL)-17 cytokines have emerged as key players in multiple inflammatory disorders, and they appear to be especially prominent in skin inflammation. IL-17 cytokines produced by T cells and other cell types potently activate keratinocytes to promote inflammation in a feed-forward loop. Given this key pathogenic role of the IL-17 pathway in autoimmune and inflammatory disease, it has been the focus of intense efforts to target therapeutically. The inflammatory effects of IL-17 can be targeted directly by blocking the cytokine or its receptor, or indirectly by blocking cytokines upstream of IL-17-producing cells. Psoriasis has been the major success story for anti-IL-17 drugs, where they have proven more effective than in other indications. Hidradenitis suppurativa (HS) is another inflammatory skin disease which, despite carrying a higher burden than psoriasis, is poorly recognized and under-diagnosed, and current treatment options are inadequate. Recently, a key role for the IL-17 pathway in the pathogenesis of HS has emerged, prompting clinical trials with a variety of IL-17 inhibitors. In this review, we discuss the roles of IL-17A, IL-17F and IL-17C in psoriasis and HS and the strategies taken to target the IL-17 pathway therapeutically.
Topics: Animals; Hidradenitis Suppurativa; Humans; Inflammation; Interleukin-17; Keratinocytes; Psoriasis; Signal Transduction; Skin; Th17 Cells
PubMed: 32379344
DOI: 10.1111/cei.13449 -
JAMA Dermatology Aug 2021Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.
OBJECTIVE
To estimate overall HS prevalence.
DATA SOURCES
This review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil's disease). No language restriction was applied.
STUDY SELECTION
Original investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.
DATA EXTRACTION AND MEASURES
Two reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.
MAIN OUTCOMES AND MEASURES
Hidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).
RESULTS
In 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.
Topics: Cross-Sectional Studies; Hidradenitis Suppurativa; Humans; Incidence; Observational Studies as Topic; Prevalence; Regression Analysis
PubMed: 34037678
DOI: 10.1001/jamadermatol.2021.1677 -
JAMA Dermatology Nov 2021Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options.
OBJECTIVE
To evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline.
INTERVENTIONS
Participants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10).
MAIN OUTCOMES AND MEASURES
The prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores.
RESULTS
Eighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-three participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%).
CONCLUSIONS AND RELEVANCE
In this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03248531.
Topics: Adalimumab; Adult; Antibodies, Monoclonal, Humanized; Bayes Theorem; Double-Blind Method; Drug Administration Schedule; Female; Hidradenitis Suppurativa; Humans; Infant; Severity of Illness Index; Treatment Outcome
PubMed: 34406364
DOI: 10.1001/jamadermatol.2021.2905 -
Dermatology (Basel, Switzerland) 2020Hidradenitis suppurativa (HS) is a chronic painful skin disease that severely impairs patients' quality of life. While high-quality trials of HS therapies remain... (Review)
Review
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic painful skin disease that severely impairs patients' quality of life. While high-quality trials of HS therapies remain limited, medical knowledge of best treatment practices is rapidly evolving, leading to the recent publication of multiple international treatment guidelines for HS.
SUMMARY
This review compares international HS treatment guidelines, describes evidence for effectiveness of common and emerging HS therapies, and provides guidance for integrating evidence-based HS care into practice. Although over 50 medical and procedural treatments are mentioned across international HS guidelines, only adalimumab and infliximab have grade B/weak recommendation or higher across all major guidelines. This review describes the appropriate patient selection and effectiveness of the most commonly used medical and procedural treatments for HS. It also includes recommendations for counseling, dosing, and duration of medical therapies as well as procedure videos for the practicing dermatologist.
Topics: Adalimumab; Anti-Bacterial Agents; Dermatologic Agents; Dermatologic Surgical Procedures; Dermatology; Hidradenitis Suppurativa; Humans; Infliximab; Internationality; Practice Guidelines as Topic
PubMed: 32408306
DOI: 10.1159/000507323 -
Medicina (Kaunas, Lithuania) Apr 2023: Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil's disease, is a chronic, inflammatory, recurrent, and debilitating skin disease of the hair... (Review)
Review
: Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil's disease, is a chronic, inflammatory, recurrent, and debilitating skin disease of the hair follicles characterized by inflammatory, painful, deep-rooted lesions in the areas of the body characterized by the presence of the apocrine glands. Unfortunately, huge unmet needs still remain for its treatment. : The purpose of our review was collecting all cases, case series, trials, and ongoing studies available in the literature on the use of this class of drugs for HS. : The investigated manuscripts included trials, reviews, letters to the editor, real-life studies, case series, and reports. Manuscripts were identified, screened, and extracted for the relevant data following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. : We selected 56 articles of which 25 met the selection criteria for our review. Among the JAK inhibitors to date, there is only one published clinical trial in the literature (Janus kinase 1 inhibitor INCB054707), a real-life study with 15 patients up to week 24 in which upadacitinib was used and a case series where tofacitinib was successfully used. Conversely, there are several ongoing clinical trials. : Results to date in the literature show promising levels of efficacy and the safety of JAK inhibitors in HS. Several clinical trials are underway from which it will be very important to compare the available data. There are still too few studies conducted with a low sample size, so it remains critical to investigate this issue further in the future with a real-life study involving a large sample of patients in order to provide safe and viable therapeutic alternatives for HS.
Topics: Humans; Hidradenitis Suppurativa; Janus Kinase Inhibitors
PubMed: 37109759
DOI: 10.3390/medicina59040801 -
Journal of the European Academy of... Jan 2019Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and...
Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.
Topics: Adalimumab; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biological Products; Comorbidity; Consensus; Delphi Technique; Hidradenitis Suppurativa; Humans; Practice Guidelines as Topic; Smoking
PubMed: 30176066
DOI: 10.1111/jdv.15233 -
Vascular Health and Risk Management 2022According to data from the American Heart Association and the World Health Organization, cardiovascular disease (CVD) is the most frequent cause of premature death.... (Review)
Review
According to data from the American Heart Association and the World Health Organization, cardiovascular disease (CVD) is the most frequent cause of premature death. Several inflammatory and non-inflammatory skin diseases have been associated with metabolic syndrome and cardiovascular risk (CVR). Here, we classified these conditions into traditionally CVR-associated and those that have been linked to a lesser degree. Psoriasis and hidradenitis suppurativa are commonly associated with CVD, sharing common inflammatory pathways and a higher prevalence of traditional cardiovascular risk factors. Many other diseases could be associated indirectly - with no common pathogenic features with the atheromatous disease - but share a higher prevalence of standard cardiovascular risk and chronic inflammatory state. This review aims to highlight the associated cardiovascular risk that exists for some dermatologic diseases and sensitize cardiologists, dermatologists, and first care providers to implement risk factor control promptly.
Topics: Cardiovascular Diseases; Hidradenitis Suppurativa; Humans; Metabolic Syndrome; Psoriasis; Skin
PubMed: 35210782
DOI: 10.2147/VHRM.S343319