Defining a Minimal Effective Serum Trough Concentration of Secukinumab in Psoriasis: A Step toward Personalized TherapyThe armamentarium of psoriasis treatments has been reinforced by the introduction of biologics that target IL-17A (European Medicines Agency, 2015; Frieder et al., 2018), and at present, achieving complete skin clearance has become a realistic goal. However, in clinical practice, physicians encounter various levels of responses, including insufficient response or loss of response with anti–IL-17A treatment. This has led to physicians exploring off-label intensification regimens through trial and error, either by increasing the dose or by shortening the administration intervals (Beecker and Joo, 2018; Phung et al., 2018).
Impact of Secukinumab on Endothelial Dysfunction and Other Cardiovascular Disease Parameters in Psoriasis Patients over 52 WeeksPsoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA (Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated with Secukinumab) was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomly assigned to receive 300 mg or 150 mg secukinumab until week 52 or to receive placebo until week 12 and then 300 mg or 150 mg secukinumab until week 52.
Online Care Versus In-Person Care for Improving Quality of Life in Psoriasis: A Randomized Controlled Equivalency TrialThis 12-month, pragmatic, randomized controlled equivalency trial evaluated whether an online, collaborative connected-health model results in equivalent improvements in quality of life compared with in-person care for psoriasis. Overall, 296 adults with physician-diagnosed psoriasis from ambulatory clinics were randomly assigned to either online or in-person care; all were analyzed for outcomes. In the online group, patients and primary care providers sought dermatologists’ care directly and asynchronously online.
Defining the Therapeutic Range for Adalimumab and Predicting Response in Psoriasis: A Multicenter Prospective Observational Cohort StudyBiologics have transformed management of inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by circulating drug levels has been proposed. We aimed to determine the real-world clinical utility of therapeutic drug monitoring in psoriasis. Within a multicenter (n = 60) prospective observational cohort, 544 psoriasis patients were included who were receiving adalimumab monotherapy and had at least one serum sample and Psoriasis Area and Severity Index (PASI) score available within the first year.
Incidence and Risk of Inflammatory Bowel Disease in Patients with Psoriasis—A Nationwide 20-Year Cohort StudyIn psoriasis patients, incidence rates of Crohn disease (CD) and ulcerative colitis (UC) have been increased in epidemiological studies and certain clinical trials, yet the association remains poorly understood. We studied a 20-year nationwide cohort of 235,038 Danish adults with psoriasis and a 1:1 matched reference group. Less than 1% of psoriasis patients developed CD or UC during follow-up. Incidence rates of CD were highest for younger women with psoriasis and patients with concurrent psoriatic arthritis, whereas men with psoriasis had particularly high incidence rates of UC compared with their non-psoriasis peers.
Risk of Serious Infection, Opportunistic Infection, and Herpes Zoster among Patients with Psoriasis in the United KingdomThe risk of infection among patients with psoriasis of varying severity in a broadly representative population remains poorly understood. Using The Health Improvement Network (THIN), an electronic medical records database representative of the general UK population, we performed a cohort study to determine the risks of serious infection, opportunistic infection, and herpes zoster among patients with versus without psoriasis and according to psoriasis severity. We identified 187,258 patients with mild and 12,442 patients with moderate to severe psoriasis based on treatment patterns.
Intentional and Unintentional Medication Non-Adherence in Psoriasis: The Role of Patients’ Medication Beliefs and Habit StrengthMedication non-adherence is a missed opportunity for therapeutic benefit. We assessed “real-world” levels of self-reported non-adherence to conventional and biologic systemic therapies used for psoriasis and evaluated psychological and biomedical factors associated with non-adherence using multivariable analyses. Latent profile analysis was used to investigate whether patients can be categorized into groups with similar medication beliefs. Latent profile analysis categorizes individuals with similar profiles on a set of continuous variables into discrete groups represented by a categorical latent variable.
Risk of Incident Liver Disease in Patients with Psoriasis, Psoriatic Arthritis, and Rheumatoid Arthritis: A Population-Based StudyRelatively little is known about the risk for incident liver disease in psoriasis (PsO), psoriatic arthritis (PsA), and rheumatoid arthritis (RA). We performed a cohort study among patients with PsO, PsA, or RA and matched controls in The Health Improvement Network from 1994 to 2014. Outcomes of interest were any liver disease, nonalcoholic fatty liver disease, and cirrhosis (any etiology). Among patients with PsO (N = 197,130), PsA (N = 12,308), RA (N = 54,251), and matched controls (N = 1,279,754), the adjusted hazard ratios for any liver disease were elevated among patients with PsO (without systemic therapy [ST] 1.37; with ST 1.97), PsA (without ST 1.38; with ST 1.67), and RA without an ST (1.49) but not elevated in patients with RA prescribed an ST (0.96).
Differential Drug Survival of Second-Line Biologic Therapies in Patients with Psoriasis: Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74–79%), falling to 58% (55–61%) in the third year.
Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort.
Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in JapanesePsoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with heterogeneity in epidemiologic and genetic landscapes of global populations. We conducted an initial genome-wide association study and a replication study of PsV in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the single nucleotide polymorphisms with PsV risk at TNFAIP3-interacting protein 1and the major histocompatibility complex region (P = 3.7 × 10−10 and 6.6 × 10−15, respectively).
Re: Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-AnalysisWe thank Reich et al. for their correspondence on our paper (Jabbar-Lopez et al., 2017). They helpfully highlight the IXORA-S trial comparing ixekizumab with ustekinumab for moderate-severe plaque psoriasis (Reich et al., 2017). This was published after our search cutoff date and so was not included in our review.
Obesity, Waist Circumference, Weight Change, and Risk of Incident Psoriasis: Prospective Data from the HUNT StudyAlthough psoriasis has been associated with obesity, there are few prospective studies with objective measures. We prospectively examined the effect of body mass index, waist circumference, waist-hip ratio, and 10-year weight change on the risk of developing psoriasis among 33,734 people in the population-based Nord-Trøndelag Health Study (i.e., HUNT), Norway. During follow-up, 369 incident psoriasis cases occurred. Relative risk (RR) of psoriasis was estimated by Cox regression. One standard deviation higher body mass index, waist circumference, and waist-hip ratio gave RRs of 1.22 (95% confidence interval [CI] = 1.11–1.34), 1.26 (95% CI = 1.15–1.39), and 1.18 (95% CI = 1.07–1.31), respectively.
Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-AnalysisMultiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo.
All-Cause and Cause-Specific Mortality in Patients with Psoriasis in Taiwan: A Nationwide Population-Based StudyAsian population-based data evaluating all-cause mortality and cause-specific mortality in patients with psoriasis are limited. This study aimed to evaluate the risk of all-cause mortality (stratified according to onset status, disease severity, and concomitant psoriatic arthritis) and cause-specific mortality in patients with psoriasis. Our study cohort consisted of 80,167 patients with newly diagnosed psoriasis between 2001 and 2012 in the National Health Insurance Database. Vital status and cause of death were ascertained from the National Death Registry of Taiwan.
Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis: A Population-Based StudyThe factors that contribute to the development of psoriatic arthritis (PsA) among patients with psoriasis are not well known; however, systemic inflammation is believed to be important. On the basis of recent laboratory work demonstrating that major depressive disorder (MDD) is associated with increased systemic inflammation, we hypothesized that patients with psoriasis who develop MDD are at increased risk of subsequently developing PsA. We utilized The Health Improvement Network, a primary care medical records database, to identify 73,447 individuals with psoriasis.
Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the BIOBADADERM RegistryInformation regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression.
Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-AnalysisA comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria.
Increased Risk of Autoimmune Hepatitis in Patients with Psoriasis: A Danish Nationwide Cohort StudyPsoriasis is associated with autoimmune diseases, for example, diabetes and inflammatory bowel disease. A link between psoriasis and autoimmune diseases may be the dysregulation of tissue resident memory T cells (TRMs), which reside long term in peripheral tissues including the skin. This subset of T cells probably evolved to populate epithelial barriers throughout the body with protective T cells reacting to pathogens most relevant in their respective tissues (Clark, 2015; Mackay et al., 2013; Wakim et al., 2012).
Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort StudyPsoriasis and multiple sclerosis (MS) are inflammatory disorders with similarities in genetic risk variants and inflammatory pathways. Limited evidence is available on the relationship between the two diseases. We therefore investigated the risk of incident (new-onset) MS in patients with mild and severe psoriasis, respectively. All Danish citizens aged ≥ 18 years from 1 January 1997 to 31 December 2011 were identified by linkage of nationwide registries at the individual level. We estimated incidence rate ratios (IRRs) adjusted for age, gender, socioeconomic status, smoking, medication, comorbidity, and UV phototherapy by Poisson regression.