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

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.

Evaluation of the Anti-Atopic Dermatitis Effects of α-Boswellic Acid on Tnf-α/Ifn-γ-Stimulated HaCat Cells and DNCB-Induced BALB/c Mice.

Boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and anti-tumor efficacy. Atopic dermatitis is a chronic, non-infectious inflammatory skin disease. However, the effects of α-boswellic acid on atopic dermatitis have not been studied. Therefore, in this study we examined the expression level of pro-inflammatory cytokines, histopathological analysis, and physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene and TNF-α/IFN-γ-stimulated HaCaT cells to better understand the agent's anti-atopic dermatitis efficacy. First, we found that α-boswellic reduced the epidermal thickening, mast cell numbers, and dermal infiltration of 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in BALB/c mice. Furthermore, we also found that α-boswellic acid can restore transepidermal water loss and skin reddening in mice. In human keratinocytes inflamed by TNF-α/IFN-γ, α-boswellic acid inhibited MAP kinase activation and showed a reduction in NF-κB nuclear translocation. Finally, α-boswellic acid can reduce the expression level of cytokines (IL-1ß, IL-6, and IL-8) following the stimulation of TNF-α/IFN-γ in HaCaT cells. Taken together, our study suggests that α-boswellic acids are a potential component for the development of anti-atopic dermatitis drugs.

Overlapping Features of Psoriasis and Atopic Dermatitis: From Genetics to Immunopathogenesis to Phenotypes.

Psoriasis (PSO) and atopic dermatitis (AD) were once considered to be mutually exclusive diseases, but gradually regarded as a spectrum of disease. Shared genetic loci of both diseases were noted in some populations, including Chinese. Shared immunopathogenesis involving Th17, Th1, Th22 cells, or even IL-13 was found in certain stages or phenotypes. This review discusses the overlapping genetic susceptibility, shared cytokines, immune-mediated comorbidities, and clinical presentations. Overlapping conditions could be classified into mainly PSO lesions with AD features or vice versa, concomitant PSO and AD, or disease transformation as a result of biologics treatment.

Switching biologics in psoriasis - practical guidance and evidence to support.

INTRODUCTION: Advances of biologic agents have changed the treatment paradigm of psoriasis to higher efficacy and better quality of life. However, the demand for biologic switch is increasing due to patient's greater expectation and decreasing efficacy in long-term use. Also, biologic-induced adverse effects necessitate the switching of biologics. AREAS COVERED: This review article was divided into two parts. The first part focused on the biologic switch due to lack of efficacy. The second part provided switching suggestions related to adverse effects. EXPERT COMMENTARY: Biologic switch in psoriasis was mainly due to lack of efficacy, and the subsequent biologic agent was usually given at the next scheduled time point without washout period. In pivotal randomized controlled trials, patients with poor response to TNF-alpha inhibitors and ustekinumab achieved better efficacy after switching to IL-23 and IL-17 inhibitors. In addition, real-world data showed that intra-class switch could still achieve a 50%-80% of PASI 75 response in individuals with anti-IL-17 failure histories. As for the biologic switch due to adverse effects, washout period was recommended and transition to a biologic agent with different modes of action was preferred, especially class-specific adverse events.

A review of antibiotics and psoriasis: induction, exacerbation, and amelioration.

Introduction: Psoriasis is affected by many environmental factors, including infections and antibiotics. However, the relationship between antibiotics and psoriasis is inadequately studied. Some antibiotics were listed as triggering factors; others showed benefit for psoriasis control. The aim of this article is to review current evidence that may help identify appropriate antibiotics for patients with psoriasis. Areas covered: The PubMed, Embase, Clinicalkey databases, and google scholar were searched for relevant articles published up to May 2019. Literature regarding antibiotics and psoriasis were included. Six randomized controlled trials and four controlled or cohort studies were identified in 13 kinds of antibiotics. Expert opinion: Macrolides and rifampin showed decrease of psoriasis area and severity index score in plaque-type psoriasis, while penicillin revealed no statistically significant improvement in guttate psoriasis. Previously tetracyclines were considered as triggering factors, but data were found only in cases or retrospective studies. Mechanisms were thought to be related to immunomodulation rather than bacteria inhibition. Research gap in the influence of genetic susceptibility, the impact on microbiota, and the mode of actions remain to be investigated.

Itraconazole in the Treatment of Nonfungal Cutaneous Diseases: A Review.

INTRODUCTION: The anti-inflammatory and pro-kinetic properties of antibiotics have been widely reported. However, the non-antifungal properties of antifungal agents are less well known and less explored in clinical practice. The purpose of this review was to survey the literature on the non-antifungal use of itraconazole in dermatological practice and the possible modes of action of this agent. METHODS: The PubMed database was searched for relevant articles published up to January 2017. The references in the articles identified by the search were then hand-searched for additional relevant publications. RESULTS: Itraconazole displays a great diversity of non-antifungal activity and has been used to treat a broad spectrum of diseases. The results of our survey reveal that itraconazole has the potential to be an alternative agent for treating patients with advanced cancer (either alone or in combination with other cytotoxic chemotherapeutic drugs), especially those refractory to traditional treatments. Moreover, itraconazole acts as an anti-angiogenesis agent, induces nail growth, and modulates inflammatory or immune diseases. CONCLUSION: Oral antifungal agents have many non-antifungal properties. However, the body of evidence on individual agents often remains limited due to the lack of large-scale randomized controlled studies. Although some of the findings published to date seem promising, pharmacological vigilance should be taken for off-label use in real-world practice.

Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

Anti-interleukin and interleukin therapies for psoriasis: current evidence and clinical usefulness.

Anti-interleukin (IL) therapies have emerged as a major treatment for patients with moderate-to-severe psoriasis. This article reviews the up-to-date results of pivotal clinical trials targeting the interleukins used for the treatment of psoriasis, including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IL-20, IL-22, IL-23, IL-36 and bispecific biologics IL-17A/tumor necrosis factor alpha (TNF-α). Cytokines involved in the circuits of psoriasis inflammation without ongoing clinical trials are also mentioned (IL-9, IL-13, IL-15, IL-16, IL-18, IL-19, IL-21, IL-24, IL-27, IL-33, IL-35, IL-37, and IL-38).

A postmenopausal woman with sciatica from broad ligament leiomyoma: a case report.

BACKGROUND: Unilateral lower abdominal pain and/or sciatic nerve pain is a common presentation in the elderly population. The prevalence of broad ligament leiomyoma is <1 % with the prevalence declining after the menopause and it is rare for broad ligament leiomyomas to be clinically significant. Thus, we highlight a case of symptomatic broad ligament leiomyoma in a postmenopausal woman whose symptoms improved after definitive treatment. CASE PRESENTATION: A 62-year-old postmenopausal Macedonian woman was referred to our gynecological department with unexplained pain in her left leg and left iliac fossa region on walking. There was minimal relief with increasing analgesia use prescribed by the family physician. Investigations revealed an ipsilateral adnexal mass and subsequent treatment with laparoscopic broad ligament myomectomy helped to alleviate her symptoms. CONCLUSIONS: Our case highlights the importance of staying mindful of alternate diagnoses when presented with a common presentation of iliac fossa pain and pain in the leg. Although broad ligament leiomyomas are benign tumors, the uncommon symptomatic presentation led us to report and focus some attention on this type of tumor.

Diabetes and poor glycaemic control in rural patients with coronary artery disease.

BACKGROUND: The burden of cardiovascular disease is higher in rural populations. Existing data on rural cardiovascular health is mainly based on community surveys. Regional differences are not well addressed. This study aims to identify regional inequalities in cardiovascular risk factors (CVRFs) in Australian patients with suspected coronary artery disease. METHODS AND RESULTS: 538 subjects (72% male; mean age 63years) were recruited from a single cardiac catheter laboratory over a 24-month period. Subjects were stratified into Remoteness Areas (RAs) according to the Australian Standard Geographical Classification (RA1 corresponds to Major Cities, RA2 to Inner Regional Areas, RA3 to Outer Regional Areas). Body-mass index, blood pressure, hypertension, dyslipidaemia, diabetes and smoking history were recorded. A blood sample taken before the angiogram was analysed for lipids and fasting blood glucose (FBG). Distribution of the study population across RA1, RA2 and RA3 was 34.8%, 46.1% and 19.1%. Only FBG (p=0.019) and diagnosed diabetes (p=0.009) were significantly different i.e. higher in RA1. Of those without known diabetes, RA3 had the highest prevalence of dysglycaemia (p=0.023) with two-thirds having either pre-diabetes or undiagnosed diabetes. Logistic regression showed that age and RA3 were the only statistically significant predictors of elevated FBG. CONCLUSION: CAD patients from remote Australia had higher rates of pre-diabetes, undiagnosed diabetes and poorer glycaemic control. Analysis of the main CVRFs revealed a regional inequality in the recognition and management of diabetes alone. Attention to this gap in rural and urban healthcare is crucial to future cardiovascular health outcomes in Australia.

Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells.

Prostate cancer is one of the leading causes of cancer death in men in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of prostate cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as pterostilbene. As a constituent of small fruits such as grapes, berries, and their products, pterostilbene is under intense investigation as a cancer chemopreventive agent. Using the p53 wild type LNCaP and p53 null PC3 cells, we found that treatment with pterostilbene resulted in dose-dependent inhibition of cellular proliferation, which suggested that the interaction of pterostilbene with the p53 might not fully explain its inhibitory effect on proliferation. In this study, we found that pterostilbene activated AMPK in both p53 positive and negative human prostate cancer cells. Pterostilbene-activated AMPK decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the resolution between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive LNCaP cells, pterostilbene blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, pterostilbene induced apoptosis in p53 negative PC3 cells. Our results suggest that pterostilbene may be a functional chemopreventive agent and that dietary exposure to pterostilbene would be helpful for antiprostate cancer activity.