Background: Guselkumab is an interleukin-23 inhibitor indicated for treatment of moderate-to-severe plaque psoriasis. Objective: The objective was to determine the relative efficacy and safety of guselkumab compared to other biologics. Methods: A systematic review was performed to identify randomized controlled trials (RCTs). Bayesian network meta-analyses (NMAs) were conducted using meta-regression analyses that adjusted for cross-trial differences and risk differences. The primary outcome was Psoriasis Area and Severity Index (PASI) 90 response. Other efficacy and safety outcomes were considered. Several meta-regressions were performed to account for variations in patient and study characteristics: baseline risk adjustment (ie, control group response), prior biologic use, duration of psoriasis, weight, age, race, and baseline PASI/dermatology life quality index scores. The best-fitting model using predefined criteria was selected. Results: Forty-five RCTs were identified. Patient and study characteristics differed between RCTs as reflected in variations in control group response. Both the baseline risk-adjusted NMA and the risk-difference NMA fit the data best and suggested guselkumab has one of the highest PASI 90 responses. Pairwise comparisons from the baseline risk-adjusted PASI 90 NMA suggested guselkumab has comparable efficacy with ixekizumab (relative risk [RR]: 0.999, 95% credible intervals [CrIs]: 0.89-1.13) and brodalumab (RR: 1.04, 95% CrIs: 0.91-1.17) and superior efficacy versus all other treatments in the network (RR range, 1.20 to 43.22). Guselkumab was superior or comparable to other therapies for other efficacy outcomes and had a more favorable safety profile than most. Conclusions: Guselkumab has one of the highest PASI 90 responses among psoriasis treatments; similar findings were observed for other efficacy outcomes. Guselkumab has a favorable benefit-risk balance compared to moderate-to-severe psoriasis therapies.

Grade IV glioma (glioblastoma) is one of the most common brain/central nervous system cancers. In 2005, the standard of care for adjuvant treatment was significantly changed with the approval of temozolomide. Carmustine wafers have also gained some popularity. Phase III trials are currently evaluating bevacizumab in conjunction with the standard temozolomide regimen. Despite these recent advances in pharmacotherapy, roughly two-thirds of patients do not survive longer than 2 years after diagnosis. Meanwhile, the costs of treatment are substantial. The goal of this study is to review the clinical, cost-of-illness, and cost-effectiveness literature relevant to treating glioblastoma. Estimates of the economic burden of glioblastoma within different healthcare systems were converted to 2013 US dollars. Temozolomide has demonstrated a 2.5-month increase in overall survival and a 1.9-month increase in progression-free survival, relative to radiotherapy alone. Carmustine wafers have also been shown to increase overall survival by 2.3 months, compared with placebo wafers. Cost-effectiveness studies of temozolomide have produced incremental cost-effectiveness ratios, adjusted to 2013 US dollars, with a range from US$73,586 per quality-adjusted life-year (QALY) (UK National Health Service perspective) to US$105,234 per QALY (US societal perspective). More research is needed to quantify the full societal burden of illness.

Summary Background Total work productivity loss (WPL) and associated indirect costs contribute to the economic burden of psoriasis. Objectives To estimate total WPL and related indirect costs, and identify predictors of WPL associated with psoriasis severity in France, Germany, Spain, the U.K. and Italy (EU5) and the U.S.A. Methods Data from the 2015 Adelphi Real World Psoriasis Disease Specific Programme, analysed for absenteeism, presenteeism and total WPL, were quantified (0–100%) from participants who completed the Work Productivity and Activity Impairment (WPAI) instrument. These measures were converted to indirect costs using the human capital method. Univariate and multivariate statistical analyses controlling for patient demographic and clinical characteristics were conducted. Results Of the 936 respondents (29·6% U.S.A., 70·4% EU5) who completed the WPAI, 32·6%, 40·7% and 26·6% had mild [body surface area (BSA) 0–2%], moderate (BSA 3–10%) and severe (BSA > 10%) psoriasis, respectively. Average age, Dermatology Life Quality Index (DLQI) score and BSA were, respectively, 42·4 years, 5·1 and 9·6%; and 37·2% of respondents were female. Mean percentages of total WPL for respondents with mild, moderate and severe psoriasis were 10·1%, 18·9% and 29·4%, respectively. Presenteeism contributed considerably more to total WPL than did absenteeism across all countries and disease severity classes. Mean annual indirect costs per patient due to WPL ranged from 3742 U.S. dollars in Spain to 9591 U.S. dollars in the U.S.A. Multivariate regression showed that a one‐unit increase in DLQI score increases total WPL by 1·8% (P < 0·001). Conclusions WPL increased progressively with increasing DLQI scores and BSA, confirming the relationship between psoriasis severity and its economic burden. What's already known about this topic? The economic burden of psoriasis is exceptionally high given the high prevalence and lifelong nature of the condition. Several studies have attempted to assess the overall economic burden of psoriasis but there is a lack of comparative data from different countries, and issues around inconsistent methodologies, including statistical analyses. Total work productivity loss (WPL) and associated indirect costs are believed to contribute to the economic burden of psoriasis. What does this study add? This study measured total WPL and indirect costs via the same method and at the same time point in the U.S.A., France, Germany, Spain, U.K. and Italy. Total WPL increased progressively with psoriasis disease severity. Disease severity and Dermatology Life Quality Index scores significantly correlated with WPL after controlling for patient demographic and clinical characteristics. The U.S.A. had the highest annual mean indirect costs associated with total WPL. Linked Comment: Drabo et al. Br J Dermatol 2020; 183:420–421.

Under typical US willingness-to-pay cutoffs, ustekinumab 90 mg is not cost effective compared with etanercept 50 mg therapy in moderate to severe psoriasis patients for the base-case 3-year time horizon. Ustekinumab 45 mg dominates etanercept 50 mg therapy for an equivalent patient psoriasis severity and time horizon.

Aim: The importance of adjusting for cross-study heterogeneity when conducting network meta-analyses (NMAs) was demonstrated using a case study of biologic therapies for moderate-to-severe plaque psoriasis. Methods: Bayesian NMAs were conducted for Psoriasis Area and Severity Index 90 response. Several covariates were considered to account for cross-trial differences: baseline risk (i.e., placebo response), prior biologic use, body weight, psoriasis duration, age, race and baseline Psoriasis Area and Severity Index score. Model fit was evaluated. Results: The baseline risk-adjusted NMA, which adjusts for multiple observed and unobserved effect modifiers, was associated with the best model fit. Lack of adjustment for cross-trial differences led to different clinical interpretations of findings. Conclusion: Failure to adjust for cross-trial differences in NMA can have important implications for clinical interpretations when studying the comparative efficacy of healthcare interventions.