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.

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.

Background A systematic review and meta-analysis was conducted to assess breast cancer (BC) outcomes among patients with early-stage hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) BC, receiving adjuvant endocrine therapy. Methods Randomized controlled trials (RCTs) and real-world evidence (RWE) studies were identified using Ovid MEDLINE®, Embase, and Evidence-Based Medicine Reviews. Clinical and methodological similarities including alignment of outcome definitions with standardized definitions for efficacy endpoints criteria were assessed to evaluate feasibility of conducting a meta-analysis. Where feasible, 5-year probabilities of BC recurrence or death were estimated using a Bayesian hierarchical arm-based model. Results Of 21 included studies, 8 RCTs and 4 RWE studies reported outcome data of interest. There was heterogeneity in outcome reporting, as well as variation in recurrence risk amongst studies with aligned reporting. Of the 12 studies, 10 were considered for inclusion in a meta-analysis of BC recurrence or death. Only a subgroup analysis of node-positive patients (3 studies; n = 7307) was deemed feasible. The 5-year probability of BC recurrence or death was 17.2% (95% credible interval: 14.6%–20.3%). Conclusion Although studies reporting recurrence outcomes were limited, there remains a high risk of BC recurrence, especially among node-positive patients. Approximately 1 in 6 women with node-positive HR+/HER2- early-stage BC receiving endocrine therapy experience recurrence or death within 5-years of initiating treatment, suggesting a need for novel treatments for this population.

OBJECTIVE Long-term outcomes of single-level lumbar arthroplasty are understood to be very good, with the most recent Investigational Device Exemption (IDE) trial showing a < 5% reoperation rate at the close of the 7-year study. This post hoc analysis was conducted to determine whether specific patients from the activL IDE data set had better outcomes than the mean good outcome of the IDE trial, as well as to identify contributing factors that could be optimized in real-world use. METHODS Univariable and multivariable logistic regression models were developed using the randomized patient set (n = 283) from the activL trial and used to identify predictive factors and to derive risk equations. The models were internally validated using the randomized patient set and externally validated using the nonrandomized patient set (n = 52) from the activL trial. Predictive power was assessed using area under the receiver operating characteristic curve analysis. RESULTS Two factors were significantly associated with achievement of better than the mean outcomes at 7 years. Randomization to receive the activL device was positively associated with better than the mean visual analog scale (VAS)–back pain and Oswestry Disability Index (ODI) scores, whereas preoperative narcotics use was negatively associated with better than the mean ODI score. Preoperative narcotics use was also negatively associated with return to unrestricted full-time work. Other preoperative factors associated with positive outcomes included unrestricted full-time work, working manual labor after index back injury, and decreasing disc height. Older age, greater VAS–leg pain score, greater ODI score, female sex, and working manual labor before back injury were identified as preoperative factors associated with negative outcomes. Preoperative BMI, VAS–back pain score, back pain duration ≥ 1 year, SF-36 physical component summary score, and recreational activity had no effect on outcomes. CONCLUSIONS Lumbar total disc replacement for symptomatic single-level lumbar degenerative disc disease is a well-established option for improving long-term patient outcomes. Discontinuing narcotics use may further improve patient outcomes, as this analysis identified associations between no preoperative narcotics use and better ODI score relative to the mean score of the activL trial at 7 years and increased likelihood of return to work within 7 years. Other preoperative factors that may further improve outcomes included unrestricted full-time work, working manual labor despite back injury, sedentary work status before back injury, and randomization to receive the activL device. Tailoring patient care before total disc replacement may further improve patient outcomes.

A nested case-control study among 137 nursing home residents who did not receive antimicrobials, of whom 44 acquired a multidrug-resistant organism, was performed. Risk factors for acquisition included gastrointestinal medications that affect the gut microbiome, number of visits from healthcare workers, pressure ulcers, and not residing in a dementia unit.