Primary imputation methods impact efficacy results in hidradenitis suppurativa clinical trials.
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SUBMITTER: Frew JW
PROVIDER: S-EPMC7369223 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin.ObjectivesWe aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods.MethodsImmune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence.ResultsEpidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1β, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1β expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated.ConclusionsOur findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1β but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.
| S-EPMC9298903 | biostudies-literature
Project description:Elevated BMI in Hidradenitis Suppurativa is associated with decreased response to Adalimumab therapy. BMI is proposed to segregate distinct disease subtypes. It remains unresolved whether a threshold BMI exists above which increased dosages may provide clinical benefit. Individual patient data from 578 PIONEER Phase 3 participants were analyzed. Descriptive, multivariable regression analysis and receiver operating characteristic (ROC) curves were calculated to assess the relationship between BMI and clinical outcome measures using R v3.5.3. Participants in the overweight and obese BMI category had reduced odds (58 and 67%, respectively) of achieving HiSCR [OR = 0.42 (95%CI -0.19, 0.91) p = 0.03], [OR = 0.33 (95%CI 0.16, 0.67) p = 0.002] compared to participants with BMI < 25. Reduction in AN count and IHS4 score was not significantly associated. ROC analysis did not reveal any cut off value predictive of treatment outcome. No correlation between BMI and baseline disease activity or covariate interactions were identified. These findings suggest BMI is a significant covariate in the setting of lower baseline disease activity, supporting the concept of disease heterogeneity and differential therapeutic response to Adalimumab.
| S-EPMC8257943 | biostudies-literature
Project description:ImportanceFew simplified instruments exist for use in hidradenitis suppurativa (HS) trials.ObjectiveTo assess psychometric properties of the Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) score using a clinical trial data set.Design, setting, and participantsThis retrospective analysis of a phase 2 randomized double-blind, placebo-controlled, active-reference arm trial (UCB HS0001) included adults with moderate-to-severe HS.ExposuresTrial participants were randomized at baseline to receive bimekizumab, adalimumab, or placebo.Main outcomes and measuresThe HS-IGA score at prespecified time points up to 12 weeks after randomization.ResultsThe HS-IGA score showed strong convergent validity with IHS4 and HS-PhGA scores at baseline (Spearman correlation, 0.86 [P < .001] and 0.74 [P < .001], respectively) and at week 12 (Spearman correlation, 0.73 [P < .001] and 0.64 [P < .001], respectively). The HS-IGA scores assessed during predosing visits at screening and baseline showed good test-retest reliability (intraclass correlation coefficient [ICC] = 0.92). At week 12, HS-IGA responders were significantly associated with HiSCR-(50/75/90) responders (χ2 = 18.45; P < .001; χ2 = 18.11; P < .001; and χ2 = 20.83; P < .001, respectively). The HS-IGA score was predictive of HiSCR-50/75/90 and HS-PhGA response at week 12 (AUC, 0.69, 0.73, 0.85, and 0.71, respectively). However, the HS-IGA as a measure of disease activity showed low predictive validity with patient-reported outcomes at week 12.Conclusions and relevanceThe HS-IGA score demonstrated good psychometric properties compared with existing measures and may be considered for use as an end point in clinical trials for HS.
| S-EPMC10134037 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a chronic debilitating disorder that can affect any areas bearing apocrine glands. Perineal HS is associated with high morbidity compared with other anatomic regions. Early-stage disease may mimic various other forms of cutaneous disorders, but as HS progresses pathognomonic skin changes occur. Clinical stage can guide the therapeutic approach, but the lowest recurrence rate is obtained by removing all involved skin and subcutaneous fat. Pruritus ani is a complex disease with a multitude of etiologies. Its management can be frustrating and disappointing for the patient and doctor alike. The key is to start with simple treatment options focusing on perianal hygiene and avoidance of the most common offending foods and beverages. If these measures fail, topical medications should be attempted before graduating to perianal injections of methylene blue as a last resort.
| S-EPMC3140336 | biostudies-other
Project description:BackgroundThe European hidradenitis suppurativa (HS) guidelines recommend a multidisciplinary approach for patients with HS and management of comorbidities.ObjectiveWe aimed to describe the organization of a multidisciplinary HS program and characterize the patient population.MethodsWe conducted a retrospective study of patients with HS undergoing prospectively defined multidisciplinary work-up including examinations by a dermatologist, plastic surgeon, smoking specialist, and nutritionist in our outpatient unit between October 2015 and January 2017.ResultsThe study included 49 patients with a sex ratio of 1:1. A total of 73.4% of patients were smokers, 20.4% were overweight, 48.9% were obese, and 30.6% had symptoms of depression. The mean Sartorius score was 30.4 (±17.6). The outcome of plastic surgery consultation was as follows: 16 patients had operations, 5 were excluded based on medical history, 9 refused surgery, and 16 remained undecided. The refusal rates for consulting with the smoking cessation and nutrition specialists were 55.8% and 69.5%, respectively. Twelve patients received antibiotics, 9 received biologics, 9 underwent medico-surgical treatment, 9 underwent surgery, and 10 were lost to follow-up. The mean visual analogue scale score for satisfaction was 8.3 (±1.6; n = 28).ConclusionAn integrated multidisciplinary care model for HS is associated with high patient satisfaction. Adherence to the proposed comorbidity management was higher in female patients and related to empathetic interactions with physicians.
| S-EPMC7330447 | biostudies-literature
Project description:BackgroundAdalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS.MethodsWe performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using "The Grading of Recommendations Assessment, Development, and Evaluation" approach, and number-needed-to-treat (NNT) was calculated.ResultsFive randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35-2.29; trial sequential analysis TSA-adjusted CI 1.01-3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = -0.45, 95% CI = -0.76 to -0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD -0.47, 95% CI -0.61 to -0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo.ConclusionsAdalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.
| S-EPMC8183777 | biostudies-literature
Project description: Not available
| S-EPMC6464653 | biostudies-literature
Project description:BackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory condition that can have a large negative impact on health-related quality of life (HRQOL). A reliable and validated measure of HS-specific HRQOL in clinical studies is needed.ObjectivesTo develop and validate the Hidradenitis Suppurativa Quality Of Life (HiSQOL©) scale, for clinical trial measurement of HS-specific HRQOL.MethodsIn stage 1, qualitative concept elicitation interviews were conducted with patients with HS in Denmark (n = 21) and the U.S.A. (n = 21). In stage 2, cognitive debriefing interviews were performed with U.S. (n = 30) and Danish patients with HS (n = 30). In stage 3 an observational study of 222 patients with HS in the U.S.A. was conducted for item reduction, measure validation and assessment of psychometric properties. In stage 4, an observational study of 215 patients with HS in Denmark was conducted to confirm the psychometric structure derived in stage 3. In both studies the Dermatology Life Quality Index, Hospital Anxiety and Depression Scale and numerical rating scale for pain were also included.ResultsIn concept elicitation, 99 items were generated, which were reduced to 41 after removing duplicates. In cognitive debriefing, two items were added and one item removed. A 42-item instrument was psychometrically assessed. Based on psychometric analyses and patient input, the instrument was reduced to 17 items that had strong psychometric properties in both the U.S. and Danish samples.ConclusionsThe HiSQOL is a reliable and valid instrument to measure HS-specific HRQOL in clinical trials.
| S-EPMC7205560 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the skin with a predilection for women. The role of sex hormones, including estrogen and progesterone, is incompletely understood, but alterations in hormone levels may play a role in disease activity for many patients. Specific clinical considerations should be made for women with HS, particularly in the setting of pregnancy, childbirth, breastfeeding, and menopause. Current knowledge gaps regarding HS include the cumulative impact of disease across an individual's lifespan, as well as the mechanistic role of sex hormones in the disease. An improved understanding of the pathophysiologic role of hormones in HS would optimize our ability to use targeted therapies for hormonally driven disease. Psychological and psychosexual support for women with HS is an important facet of any holistic management strategy for the disease. This article integrates up-to-date pathogenic and mechanistic insights with evidence-based clinical management to optimize care for women with HS.
| S-EPMC8714605 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) leads to disfigurement and painful eruptions in terminal hair follicles of the intertriginous skin, mainly of axillary, genitofemoral, and perianal sites. It is associated with an excessive impairment of quality of life, psychiatric disorders, and sexual distress. Body image impairment has been linked to depression and anxiety and has been described for some dermatologic disorders but has not yet been investigated in patients with HS.To investigate whether body image is diminished in patients with HS and whether disease severity, age at onset, disease duration, obesity, depression, and anxiety are linked to body image impairment.This 12-month (August 1, 2009, to August 31, 2010) case-control study with a prospective, observational, cross-sectional design recruited 47 consecutive patients with HS entering a tertiary care center and 45 healthy control individuals matched for age, sex, and body mass index (BMI). One patient and 4 controls failed to complete the questionnaire and were excluded from the evaluation. Data analysis was performed from December 1, 2013, to February 15, 2014.The Frankfurt Body Concept Scale (FKKS) and the Hospital Anxiety and Depression Scale (HADS) were given to patients and controls. Correlations among FKKS, HADS, and disease features were calculated.Of the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6 [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P < .001), even when controlled for BMI. A correlation was found for the extent of body image disruption and BMI (r = -0.589; P < .001), HADS-depression score (r = -0.619; P < .001), and HADS-anxiety score (r = -0.340; P = .03). No association was found for the body image score and the severity of HS, age at onset of disease, and duration of disease. The body contact subscale score was the only subscale score that was not different between patients with HS and controls.Patients with HS have major body image impairment, which might lead to depression and anxiety, disorders that have been largely acknowledged in HS. This study identified another element of the psychosocial burden of patients with HS and reveals that body image could potentially be used as an outcome measure in future studies of HS.
| S-EPMC5876839 | biostudies-other