Impact of muscular symptoms and/or pain on disease characteristics, disability, and quality of life in adult patients with hypophosphatasia: A cross-sectional analysis from the Global HPP Registry.

Introduction: Hypophosphatasia (HPP) manifests in adults as fractures/pseudofractures, pain, muscle weakness, and other functional impairments. Better phenotypic disease characterization is needed to help recognize disability and treat patients with HPP. Methods: Baseline/pretreatment demographic, clinical characteristic, and patient-reported disability/health-related quality-of-life (HRQoL) data from adults (≥18 y) in the Global HPP Registry (NCT02306720) were stratified by presence of overt skeletal manifestations (skeletal group) versus muscular/pain manifestations without skeletal manifestations (muscular/pain group) and summarized descriptively. Disability was measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI), and HRQoL using the 36-item Short Form Health Survey (SF-36v2). Results: Of 468 adults, 300 were classified into the skeletal group and 73 into the muscular/pain group. The skeletal group had a higher median age at baseline (50.1 vs 44.4 y; P=0.047) but a lower median age at first HPP manifestation (12.3 vs 22.1 y; P=0.0473), with more signs and symptoms (median, 4 vs 3; P<0.0001) and involved body systems (median, 3 vs 2; P<0.0001) than the muscular/pain group. More patients in the skeletal group required any use of mobility aids (22.6% vs 3.5%, respectively; P=0.001). Six-Minute Walk test distances walked were similar between groups. SF-36v2 and HAQ-DI scores were similar between groups for physical component summary (n=238; mean [SD]: 40.2 [11.0] vs 43.6 [11.2]; P=0.056), mental component summary (n=238; mean [SD]: 43.6 [11.3] vs 43.8 [11.8]; P=0.902), and HAQ-DI (n=239; median [minimum, maximum]: 0.4 [0.0, 2.7] vs 0.3 [0.0, 2.1]; P=0.22). Conclusion: Adults with HPP experience similar QoL impairment regardless of skeletal involvement. Registration: https://clinicaltrials.gov/ct2/show/NCT02306720 and https://www.encepp.eu/encepp/viewResource.htm?id=47907, identifier NCT02306720; EUPAS13514.

Short-Term Efficacy of Biologic Therapies in Moderate-to-Severe Plaque Psoriasis: A Systematic Literature Review and an Enhanced Multinomial Network Meta-Analysis.

INTRODUCTION: Many targeted, systemic therapies have been developed for treatment of moderate-to-severe psoriasis (PsO). A network meta-analysis (NMA) allows for comparison between treatments not directly compared in randomized controlled trials (RCT). This study's objective was to compare the short-term (10-16 weeks) clinical efficacy according to the Psoriasis Area and Severity Index (PASI) among approved biologic treatments for moderate-to-severe PsO using a novel (enhanced) NMA model. METHODS: A systematic literature review (SLR) of RCTs for patients with moderate-to-severe PsO was conducted. English publications in MEDLINE, Embase, and The Cochrane Library up to March 2019 were searched. An enhanced multinomial Bayesian NMA was performed to simultaneously adjust for baseline risk and utilize the conditional nature of the PASI (50, 75, 90, and 100) levels. The model relaxes typical constraints that all treatments must have the same ranks across PASI levels. RESULTS: The SLR resulted in 319 relevant publications, of which 72 publications from 73 RCTs reporting 10- to 16-week data for at least one PASI response level (30,314 total patients) were included. Interleukin (IL) inhibitors (risankizumab, ixekizumab, brodalumab, secukinumab, and guselkumab) were the best performing treatments for achieving all PASI levels. Etanercept was outperformed by the other subcutaneous tumor necrosis factor α inhibitors. Application of an enhanced NMA model that allowed treatment rankings to differ by PASI level tested the robustness of results of previous NMAs in PsO. CONCLUSION: The results of this model confirmed that IL inhibitors are likely the best short-term treatment choices for improving all PASI levels.