Omalizumab, an Anti-IgE mAb, Receives Approval for the Treatment of Chronic Idiopathic/Spontaneous Urticaria

Omalizumab, an anti-IgE mAb, has recently been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of chronic idiopathic urticaria. Saini et al. (2014) (this issue) report on ASTERIA I, a 40-week randomized, double-blinded, placebo-controlled phase III trial evaluating omalizumab for the treatment of this disease

Persistence and Effectiveness of Non-Biologic Systemic Therapies for Moderate-Severe Psoriasis in Adults: a Systematic Review

BACKGROUND: The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized. OBJECTIVES: To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate, involving at least 100 adult patients with moderate-to-severe psoriasis, exposed to therapy for ≥ 3 months. METHODS: MEDLINE, Embase, the Cochrane Library and PubMed were searched from 1 January 2007 to 1 November 2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness [improvements in Psoriasis Area and Severity Index (PASI) or Physician's Global Assessment (PGA)]. This review was registered with PROSPERO, number CRD42018099771. RESULTS: Of 411 identified studies, eight involving 4624 patients with psoriasis were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta-analysis from being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterized, but mean discontinuation times ranged from 28 to 50 months for FAE and 7·7 to 22·3 months for methotrexate. At 12 months of follow-up, three studies reported that 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ≥ 75% reduction in PASI, and one reported that 76% of FAE-exposed patients achieved a markedly improved or clear PGA. CONCLUSIONS: The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real-world clinical practice in the past decade cannot be well described due to the inconsistency of the methods used

Assessing Response in Atopic Dermatitis: A Systematic Review of the Psychometric Performance of Measures Used in HTAs and Clinical Trials

Abstract Introduction Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. Methods A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator’s Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. Results A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Conclusion Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs

Incident Comorbidity, Resource Use, and All-Cause Mortality Associated with Prurigo Nodularis: A United Kingdom Retrospective Database Analysis

We described comorbidity, resource utilization, and mortality for patients with prurigo nodularis (PN) using data from the Clinical Practice Research Datalink. Patients with incident PN (2008–2018) were selected and matched to controls. Of 2,416 patients with PN, 2,409 (99.7%) were matched to controls. Prevalence of atopic dermatitis (relative risk [RR] = 2.571; 95% confidence interval [CI] = 2.356–2.806), depression (RR = 1.705; 95% CI = 1.566–1.856), anxiety (RR = 1.540; 95% CI = 1.407–1.686), coronary heart disease (RR = 1.575; 95% CI = 1.388–1.787), chronic kidney disease (RR = 1.529; 95% CI = 1.329–1.759), and type 2 diabetes mellitus (RR = 1.836; 95% CI = 1.597–2.111) was significantly higher for patients with PN. Subsequent risk of atopic dermatitis (hazard ratio = 6.58; 95% CI = 5.17– 8.37), depression (hazard ratio = 1.61; 95% CI = 1.30–1.99), and coronary heart disease (hazard ratio = 1.37; 95% CI = 1.09–1.74) were significantly increased. Resource utilization was increased in all settings: incidence rate ratio = 1.48 (95% CI = 1.47–1.49) for primary care, incident rate ratio = 1.80 (95% CI = 1.75–1.85) for inpatients, incident rate ratio = 2.15 (95% CI = 2.13–2.18) for outpatients, and incidence rate ratio = 1.32 (95% CI = 1.27–1.36) for accident and emergency. Respective cost ratios were 1.78 (95% CI = 1.67–1.90), 1.52 (95% CI = 1.20–1.94), 2.34 (95% CI = 2.13–2.58), and 1.55 (95% CI = 1.33–1.80). Total primary and secondary healthcare costs were £2,531 versus £1,333, a cost ratio of 1.62 (95% CI = 1.36–1.94). The adjusted hazard ratio for mortality was 1.37 (95% CI = 1.14–1.66). Patients with PN had significantly increased rates of comorbidity, healthcare resources utilization, and mortality compared with matched controls

Development and Validation of an Algorithm to Accurately Identify Atopic Eczema Patients in Primary Care Electronic Health Records from the UK.

Electronic health records hold great promise for clinical and epidemiologic research. Undertaking atopic eczema (AE) research using such data is challenging because of its episodic and heterogeneous nature. We sought to develop and validate a diagnostic algorithm that identifies AE cases based on codes used for electronic records used in the UK Health Improvement Network. We found that at least one of five diagnosis codes plus two treatment codes for any skin-directed therapy were likely to accurately identify patients with AE. To validate this algorithm, a questionnaire was sent to the physicians of 200 randomly selected children and adults. The primary outcome, positive predictive value for a physician-confirmed diagnosis of AE, was 86% (95% confidence interval = 80-91). Additional criteria increased the PPV up to 95% but would miss up to 89% of individuals with physician-confirmed AE. The first and last entered diagnosis codes for individuals showed good agreement with the physician-confirmed age at onset and last disease activity; the mean difference was 0.8 years (95% confidence interval = -0.3 to 1.9) and -1.3 years (95% confidence interval = -2.5 to -0.1), respectively. A combination of diagnostic and prescription codes can be used to reliably estimate the diagnosis and duration of AE from The Health Improvement Network primary care electronic health records in the UK