Tildrakizumab in the treatment of psoriasis: latest evidence and place in therapy.

Psoriasis is a chronic inflammatory disorder that is clinically characterized by scaly cutaneous plaques. New evidence suggests that dysregulation of interleukin (IL)-23, a key cytokine in the T-helper-17 pathway, plays a vital role in the development of psoriatic systemic inflammation. The novel biologic medication tildrakizumab is among the first drugs with specific action against IL-23 that has recently been approved by the United States Food and Drug Administration and the European Medicines Agency for moderate-to-severe psoriasis. Tildrakizumab has been shown in large randomized controlled trials to be effective in improving skin manifestations as well as enhancing quality of life outcomes in patients with psoriasis. Its simple dosing, prolonged duration of action, and mild adverse event profile make it a practical option for patients; however, only a small number of trials have investigated the clinical effectiveness of tildrakizumab, and long-term data regarding the drug's efficacy and safety are currently limited. Hence, further research is needed to better understand the risks and benefits of tildrakizumab. This review summarizes and analyzes phase I, phase II, and phase III clinical trials that investigate the mechanism, pharmacokinetics, efficacy, and safety of tildrakizumab. It also identifies areas in which additional studies are warranted to further elucidate the advantages of tildrakizumab over other biologic therapies

Emerging Methods to Objectively Assess Pruritus in Atopic Dermatitis.

INTRODUCTION:Atopic dermatitis (AD) is an inflammatory skin disease with a chronic, relapsing course. Clinical features of AD vary by age, duration, and severity but can include papules, vesicles, erythema, exudate, xerosis, scaling, and lichenification. However, the most defining and universal symptom of AD is pruritus. Pruritus or itch, defined as an unpleasant urge to scratch, is problematic for many reasons, particularly its negative impact on quality of life. Despite the profoundly negative impact of pruritus on patients with AD, clinicians and researchers lack standardized and validated methods to objectively measure pruritus. The purpose of this review is to discuss emerging methods to assess pruritus in AD by describing objective patient-centered tools developed or enhanced over the last decade that can be utilized by clinicians and researchers alike. METHODS:This review is based on a literature search in Medline, Embase, and Web of Science databases. The search was performed in February 2019. The keywords were used "pruritus," "itch," "atopic dermatitis," "eczema," "measurements," "tools," "instruments," "accelerometer," "wrist actigraphy," "smartwatch," "transducer," "vibration," "brain mapping," "magnetic resonance imaging," and "positron emission tomography." Only articles written in English were included, and no restrictions were set on study type. To focus on emerging methods, prioritization was given to results from the last decade (2009-2019). RESULTS:The search yielded 49 results in PubMed, 134 results in Embase, and 85 results in Web of Science. Each result was independently reviewed in a standardized manner by two of the authors (M.S., K.L.), and disagreements between reviewers were resolved by consensus. Relevant findings were categorized into the following sections: video surveillance, acoustic surveillance, wrist actigraphy, smart devices, vibration transducers, and neurological imaging. Examples are provided along with descriptions of how each technology works, instances of use in research or clinical practice, and as applicable, reports of validation studies and correlation with other methods. CONCLUSION:The variety of new and improved methods to evaluate pruritus in AD is welcomed by clinicians, researchers, and patients alike. Future directions include next-generation smart devices as well as exploring new territories, such as identifying biomarkers that correlate to itch and machine-learning programs to identify itch processing in the brain. As these efforts continue, it will be essential to remain patient-centered by developing techniques that minimize discomfort, respect privacy, and provide accurate data that can be used to better manage itch in AD

Psoriasiform Hailey-Hailey Disease Presenting as Erythematous Psoriasiform Plaques Throughout the Body: A Case Report

INTRODUCTION: Hailey-Hailey disease is an adult-onset skin condition characterized by lesions in the intertriginous regions of the body. The lesions can be pruritic, painful, and associated with physical and social impairment. CASE PRESENTATION: We present a case of psoriasiform Hailey-Hailey disease in a 60-year-old white woman who exhibited erythematous psoriasiform plaques in many areas of her body. The patient's condition was successfully treated with a twice-daily regimen of doxycycline, mometasone, and clindamycin. DISCUSSION: It is important to recognize this variant of Hailey-Hailey disease so it can be diagnosed and treated promptly. Hailey-Hailey disease can be treated with topical corticosteroids and antibiotics and usually is associated with a positive prognosis

Five-year analysis from the ESPRIT 10-year postmarketing surveillance registry of adalimumab treatment for moderate to severe psoriasis

BackgroundESPRIT is an ongoing, 10-year, observational registry, evaluating long-term safety and effectiveness of adalimumab treatment in routine clinical practice for patients with moderate to severe, chronic plaque psoriasis.ObjectivesInitial 5-year results are reported.MethodsTwo populations were analyzed: the “all-treated” population received 1 or more adalimumab doses in registry, continuing adalimumab treatment from a current prescription or previous study participation, and included the “new-prescription” population initiating adalimumab 4 weeks or earlier preregistry entry.ResultsData were collected from September 26, 2008, through November 30, 2013, for all-treated (n = 6059), which included new-prescription (n = 2580, 42.6%); median registry exposure was 765 and 677 days, respectively. In all-treated, rate (events per 100 patient-years of total adalimumab exposure [E/100PY]) of serious treatment-emergent adverse events (inside or outside of the registry) was 4.3 E/100PY, serious infection 1.0 E/100PY, malignancies 0.9 E/100PY (nonmelanoma skin cancers 0.6 E/100PY; melanomas <0.1 E/100PY). Standardized mortality ratio was 0.30 (95% confidence interval 0.19-0.44). Physician Global Assessment clear or minimal (effectiveness parameter) was achieved by 57.0% at 12 months and 64.7% at 60 months of treatment.LimitationsObservational data are subject to outcome-reporting bias.ConclusionNo new safety signals were observed with adalimumab treatment during this initial 5-year registry review. Observed number of deaths was below expected. As-observed effectiveness remained stable through 60 months

Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

IntroductionSleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation.MethodsOur analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average.ResultsResults from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch.ConclusionThese results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management

The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study

Background: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. Objectives: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. Methods: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. Results: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. Conclusions: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS

Comorbidities in Chilean patients with psoriasis: a Global Healthcare Study on Psoriasis

Background: Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. Aim: To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. Methods: This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. Results: In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. Conclusions: We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting