Suicidal Ideation in Medicinal Cannabis Patients: A 12-Month Prospective Study.

OBJECTIVE: To document the prevalence and correlates of suicidal ideation (SI) among individuals seeking cannabis-based medicinal products (CBMPs); to test whether SI declines or intensifies after three months of CBMP treatment and to document 12-month trajectories of depression in those reporting SI and other patients. METHOD: Observational data were available for 3781 patients at entry to treatment, 2112 at three months and 777 for 12 months. Self-reported depressed mood and SI were assessed using items from the PHQ-9. Additional data included sociodemographic characteristics and self-reported well-being. RESULTS: 25% of the sample reported SI at treatment entry and those with SI had higher levels of depressed mood (mean = 17.4 vs. 11.3; F(1,3533) = 716.5, p < .001) and disturbed sleep (mean = 13.8 vs. 12.2, F(1,3533) = 125.9, p < .001), poorer general health (mean = 43.6 vs. 52.2, F(1,3533) = 118.3, p < .001) and lower quality of life (mean = 0.44 vs. 0.56 (F(1,3533) = 118.3, p < .001). The prevalence of SI reduced from 23.6% to 17.6% (z = 6.5, p < .001) at 3 months. Twelve-month follow-up indicated a substantial reduction in depressed mood with this reduction being more pronounced in those reporting SI (mean (baseline) = 17.7 vs. mean (12 months) = 10.3) than in other patients (mean (baseline) = 11.1 vs. mean (12 months) = 7.0). CONCLUSIONS: SI is common among individuals seeking CBMPs to treat a range of chronic conditions and is associated with higher levels of depressed mood and poorer quality of life. Treatment with CBMPs reduced the prevalence and intensity of suicidal ideation.

Suicidal ideation is common among individuals seeking CBMPs for chronic conditionsIt is associated with higher levels of depressed mood and poorer quality of lifeTreatment with CBMPs reduced the prevalence and intensity of suicidal ideation.

A Comprehensive Framework for Evaluating the Value Created by Real-World Evidence for Diverse Stakeholders: The Case for Coordinated Registry Networks.

OBJECTIVES: This manuscript presents a comprehensive framework for the assessment of the value of real-world evidence (RWE) in healthcare decision-making. While RWE has been proposed to overcome some limitations of traditional, one-off studies, no systematic framework exists to measure if RWE actually lowers the burden. This framework aims to fill that gap by providing conceptual approaches for evaluating the time and cost efficiencies of RWE, thus guiding strategic investments in RWE infrastructure. METHODS: The framework consists of four components: (114th Congress. 21st Century Cures Act.; 2015. https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf .) identification of stakeholders using and producing RWE, (National Health Council. Glossary of Patient Engagement Terms. Published 2019. Accessed May 18. 2021. https://nationalhealthcouncil.org/glossary-of-patient-engagement-terms/ .) understanding value propositions on how RWE can benefit stakeholders, (Center for Drug Evaluation and Research. CDER Patient-Focused Drug Development. U.S. Food & Drug Administration.) defining key performance indicators (KPIs), and (U.S. Department of Health and Human Services - Food and Drug Administration: Center for Devices and Radiological Health and Center for Biologics Evaluation and Research. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices - Guidance for Industry and Food and Drug Administration Staff. 2017. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida .) establishing metrics and case studies to assess value. KPIs are categorized as 'better, faster, or cheaper" as an indicator of value: better focusing on high-quality actionable evidence; 'faster,' denoting time-saving in evidence generation, and 'cheaper,' emphasizing cost-efficiency decision compared to methodologies that do not involve data routinely collected in clinical practice. Metrics and relevant case studies are tailored based on stakeholder value propositions and selected KPIs that can be used to assess what value has been created by using RWE compared to traditional evidence-generation approaches and comparing different RWE sources. RESULTS: Operationalized through metrics and case studies drawn from the literature, the value of RWE is documented as improving treatment effect heterogeneity evaluation, expanding medical product labels, and expediting post-market compliance. RWE is also shown to reduce the cost and time required to produce evidence compared to traditional one-off approaches. An original example of a metric that measures the time saved by RWE methods to detect a signal of a product failure was presented based on analysis of the National Cardiovascular Disease Registry. CONCLUSIONS: The framework presented in this manuscript offers a comprehensive approach for evaluating the value of RWE, applicable to all stakeholders engaged in leveraging RWE for healthcare decision-making. Through the proposed metrics and illustrated case studies, valuable insights are provided into the heightened efficiency, cost-effectiveness, and improved decision-making within clinical and regulatory domains facilitated by RWE. While this framework is primarily focused on medical devices, it could potentially inform the determination of RWE value in other medical products. By discerning the variations in cost, time, and data utility among various evidence-generation methods, stakeholders are empowered to invest strategically in RWE infrastructure and shape future research endeavors.

Comorbidities and survival of multiple myeloma patients diagnosed in Finland between 2000 and 2021.

Advances in treatment have improved the survival of multiple myeloma (MM) patients, but the disease remains incurable. Here, in this nationwide retrospective real-world evidence (RWE) study, we report the patient characteristics, incidence, overall survival outcomes, comorbidities, and healthcare resource utilization (HCRU) of all adult MM patients diagnosed between 2000 and 2021 in Finland. A total of 7070 MM patients and their 21,210 age-, sex- and region-matched controls were included in the analysis. The average MM incidence doubled from 4.11 to 8.33 per 100,000 people during the follow-up. The average age-standardized incidence also showed a significant increase over time (2.51 in 2000 to 3.53 in 2021). An increase in incidence was particularly seen in older population, indicative of improved diagnosis praxis. The median overall survival (mOS) of the MM patients and their matched controls was 3.6 and 15.6 years, respectively. The mOS of all MM patients increased significantly from 2.8 years (2000-2004) to 4.4 years (2017-2021) during the follow-up period. Distinctively, in patients who received autologous stem cell transplantation (ASCT), the mOS was 9.2 years, while in patients who did not receive ASCT, the mOS was only 2.7 years. MM patients showed more comorbidities at index and increased HCRU than their matched controls. The longer median survival and decreased risk of death indicate improved treatment outcomes in MM patients in Finland.

Malignant melanoma in Portuguese adult population: a scoping review of the real-world evidence.

PURPOSE: Malignant melanoma is an aggressive cancer, and there is a notable dearth on epidemiology, clinical and treatment characterization within the Portuguese population. We performed a scoping review to identify real-world evidence studies focused in Portuguese adult patients with malignant melanoma. METHODS: A comprehensive search was conducted. After screening, we described the studies by design, sample size, geographics, setting, population, and outcomes reported. RESULTS: The search yielded 54 studies, mainly retrospective (79.6%). The population assessed was heterogeneous varying from patients with melanoma in general to specific types of melanoma, or even more restricted to patients with specific conditions. The evidence found was mostly concerning clinical outcomes (n=46), patients' clinical profile (n=44) and demographic characterization (n=48). Treatment information was described in 30 studies whereas only 18 reported epidemiological parameters. Studies were mainly performed by the major oncology centers in Lisbon, Oporto and Coimbra, and only two evaluated the entire Portuguese population. To allow comparability, only studies including patients with cutaneous malignant melanoma were considered (13 of the 54) for outcomes evaluation analysis. Median OS varied from 18 to 36 months, assessed after melanoma treatment. Incidence was the most reported epidemiological parameter, confirming the increasing number of cutaneous malignant melanoma patients over the years. Only one study reported prevalence and four reported mortality rates. CONCLUSIONS: The evidence found confirms the lack of information about malignant melanoma in Portugal, highlighting the need of real-world studies to assess melanoma prevalence and incidence rates, current treatment approaches, and clinical characterization of these patients.

[CAR T-cell therapy for malignant lymphoma].

Advances in understanding of the pathogenesis of B-cell lymphoma have led to development of various novel targeted therapies. Among them, CD19-targeted chimeric antigen receptor (CAR) T-cell therapies for relapsed and refractory B-cell lymphomas have shown remarkable efficacy in clinical trials, and three CAR T-cell products are now available in Japan. Real-world evidence (RWE) has shown that these products can provide comparable efficacy to clinical trials in clinical practice, where CAR T-cells were administered in patients with wider range of backgrounds. This finding will certainly broaden the role of CAR T-cell therapies in the treatment of B-cell lymphoma. However, since about half of the patients treated with CAR T-cell therapy progress thereafter, there is an urgent need for risk stratification and optimized management of refractory cases. Here, we review the results of clinical trials and RWE of CAR T-cell therapy in B-cell lymphoma.

Effectiveness and Safety of the MVA-BN Vaccine against Mpox in At-Risk Individuals in the United States (USMVAc).

The mpox 2022 outbreak was declared a public health emergency in July 2022. In August 2022, the MVA-BN vaccine received emergency use authorization in the United States (US) to target at-risk groups. This study (EUPAS104386) used HealthVerity's administrative US healthcare data to generate real-world evidence for MVA-BN vaccine effectiveness and safety to prevent mpox disease in men who have sex with men (MSM) and transgender women, the most affected population during the 2022 mpox outbreak. Fully vaccinated subjects (two doses ≥ 28 days apart) were initially matched with five unvaccinated subjects on calendar date, age, US region, and insurance type. Subjects were followed from index date (14 days after the second dose) until death or data end to ascertain mpox occurrence. After propensity score adjustment, the MVA-BN vaccine effectiveness against mpox disease was 89% (95% CI: 12%, 99%) among those fully vaccinated; attenuated to 64% (95% CI: 40%, 78%) among those with any dose and 70% (95% CI: 44%, 84%) for those with only a single dose. One pericarditis adverse event of special interest was observed when the risk window was extended to 28 days. These results contribute to the totality of evidence supporting the favorable benefit/risk profile of the MVA-BN vaccine.

Incorporating external real-world data (RWD) in confirmatory adaptive design.

Adaptive designs, such as group sequential designs (and the ones with additional adaptive features) or adaptive platform trials, have been quintessential efficient design strategies in trials of unmet medical needs, especially for generating evidence from global regions. Such designs allow interim decision making and making adjustment to study design when necessary, meanwhile maintaining study integrity and operating characteristics. However, driven by the heightened competitive landscape and the desire to bring effective treatment to patients faster, innovation in the already functional designs is still germane to further propel drug development to a more efficient path. One way to achieve this is by leveraging external real-world data (RWD) in the adaptive designs to support interim or final decision making. In this paper, we propose a novel framework of incorporating external RWD in adaptive design to improve interim and/or final analysis decision making. Within this framework, researchers can prespecify the decision process and choose the timing and amount of borrowing while maintaining objectivity and controlling of type I error. Simulation studies in various scenarios are provided to describe power, type I error, and other performance metrics for interim/final decision making. A case study in non-small cell lung cancer is used for illustration on proposed design framework.

Use of Real-World Evidence in Regulatory Decisions for Traditional Chinese Medicine: Current Status and Future Directions.

Traditional Chinese medicine (TCM) is a valuable resource unique to China with a long history of human use and clinical practice, which can be analyzed to generate real-world evidence (RWE). The Chinese government has been actively promoting regulatory reform that is in line with the characteristics of TCM, optimizing the clinical evidence system for TCM, and exploring the important role of RWE in supporting the development of new drugs and regulatory decision-making for TCM. This article aims to provide a comprehensive review of the use of RWE in regulatory decisions for TCM. Based on the characteristics of TCM, this study focuses on the application scenarios, challenges, and opportunities of RWE in TCM. And some suggestions are put forward to promote the wider application of RWE in TCM development and supervision.

Dose-response association of metformin use and risk of age-related macular degeneration among patients with type 2 diabetes mellitus: a population-based study.

Background: Recent studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) who receive metformin have a decreased risk of developing age-related macular degeneration (AMD). However, other studies have also suggested that metformin may increase the risk of AMD development. Therefore, this study investigated the association between treatment with metformin and the risk of AMD in patients with T2DM by using Taiwan' National Health Insurance Research Database. Methods: Patients who received a diagnosis of new-onset T2DM between 2002 and 2013 were enrolled in this study. The patients were divided into patients treated and not treated with metformin to evaluate the risk of AMD after 5 years of follow-up. The logistic regression was used to estimate the risk of AMD associated with the intensity of treatment with metformin. Result: A total of 7 517 patients (103.16 patients per 10,000 people) developed AMD in 5 years after DM diagnosis. After adjusting for the relevant variables, patients with T2DM treated with <5 defined daily dose (DDD)/month of metformin had a lower risk of AMD (odds ratios [OR]: 0.93; 95% confidence interval [CI]: 0.88 0.99). Patients treated with >25 DDD/month of metformin had a higher risk of AMD (OR: 1.39; 95% CI: 1.08-1.78). Conclusion: Metformin use may be associated with a risk of AMD among patients with T2DM in a dose-dependent association manner, with the greater benefit at lower DDD/month. However, higher DDD/month exhibited an increased risk of AMD.

AIT 2023: Current innovation and future outlook.

Although used for over 100 years, allergen immunotherapy (AIT) is still an indispensable tool in modern allergy managemen20t due to its potential to cure allergic diseases. Its current rapid development through the application of personalized and precision medicine approaches is strongly supported by advances in mHealth, component-resolved diagnosis (CRD)-based diagnostics, validation of novel biomarkers, advanced data management, and development of novel preparations. This review summarizes the key advances in the field and shows the perspectives for further development of next-generation AIT treatments.

A blueprint for success in real-world evidence: "glocal" approach to building capabilities and generating impactful evidence.

The past decade has seen the increasing influence and relevance of real-world data (RWD) and real-world evidence (RWE) in healthcare decision making. The value added by RWD/RWE has prompted the pharmaceutical industry to develop high performing systems and practices to harness the power of evidence generated at the global level. However, this worldwide transformation provides outstanding opportunities to support capability building within local affiliates and to impact key country-level stakeholders through resulting evidence. Therefore, we present an Evidence Blueprint Initiative, which links the global and local ("glocal") skills, and furthermore addresses the opportunities and gaps in evidence generation capabilities at the local level. Cross-functional experts were recruited at the local, regional, and global level to define best practices. A framework was developed to characterize the foundational expertise needed and to assess markets' existing capabilities. Subsequently, targeted roadmaps were developed and implemented to build capabilities in specific areas within each affiliate. The impact from the Blueprint is encouraging, resulting in improved local evidence plans, established evidence teams, enhanced RWD use and strategic implementation of patient centric science in local affiliates. The success of the Blueprint resides in empowering affiliates to realise their local evidence generation ambitions and to match them to their local context. It strengthens and expands the ties between various parts of the organisation and the external environment while building fit-for-future evidence capabilities from local affiliates.

Efficacy and safety of turoctocog alfa in patients with hemophilia A requiring surgical procedures: A multicentre retrospective study.

BACKGROUND: Turoctocog alfa is a recombinant Factor VIII used in patients with hemophilia A. The aim is to assess the real-life evidence of turoctocog alfa in surgery. STUDY DESIGN AND METHODS: Data were extracted from a national database. RESULTS: Turoctocog alfa was used for 86 surgeries (49 major and 37 minor) in 56 patients. The results are expressed as medians (interquartile range). Six (10.7%) patients had severe hemophilia A, four (7.1%) moderate, and 46 (82.2%) mild. For patients who underwent major surgeries, basal plasma FVIII coagulant activity (FVIII:C) levels were 15 IU.dL-1 (8-22). Eight (5-14) infusions were given, at a preoperative loading dose of 40.0 (35.0-45.5) IU.kg-1 and a total dose of 253.3 (125.0-507.0) IU.kg-1 . In patients who underwent minor surgeries, basal FVIII:C levels were 18 IU.dL-1 (9-31). Two (1-3) infusions were required, at a preoperative loading dose of 34.0 (28.8-38.5) IU.kg-1 and a total dose of 73.7 (37.6-122.1) IU.kg-1 . The overall clinical efficacy was judged excellent/good in 77 procedures (89.5%) and fair/poor in nine (10.5%). The fair/poor efficacy concerned seven patients (six mild hemophilia and one severe), for four urological surgeries, two dermatological procedures, one heart surgery, one ear-nose-throat procedure, and one dental avulsion in the patient with severe hemophilia. Three out of those seven patients received antiplatelet therapy. No thromboembolic events, anti-FVIII antibodies, or adverse events were reported. DISCUSSION: The efficacy and safety of turoctocog alfa were confirmed for the management of surgery in patients with hemophilia A. No adverse events were observed and overall efficacy was good.

Evaluating treatments in rare indications warrants a Bayesian approach.

Evaluating efficacy and real-world effectiveness for novel therapies targeting rare mutations or patient subpopulations with unmet needs is a growing challenge in health economics and outcomes research (HEOR). In these settings it may be difficult to recruit enough patients to run adequately powered randomized clinical trials, resulting in greater reliance on single-arm trials or basket trial designs. Additionally, evidence networks for performing network meta-analysis may be sparse or disconnected when comparing available treatments in narrower patient populations. These challenges create an increased need for use of appropriate methods for handling small sample sizes, structural modelling assumptions and more nuanced decision rules to arrive at "best-available evidence" on comparative and non-comparative efficacy/effectiveness. We advocate for greater use of Bayesian methods to address these challenges as they can facilitate efficient and transparent borrowing of information across varied data sources under flexible modelling assumptions, probabilistic sensitivity analysis to assess model assumptions, and more nuanced decision-making where limited power reduces the utility of classical frequentist hypothesis testing. We illustrate how Bayesian methods have been recently used to overcome several challenges of rare indications in HEOR, including approaches to borrowing information from external data sources, evaluation of efficacy in basket trials, and incorporating non-randomized studies into network meta-analysis. Lastly, we provide several recommendations for HEOR practitioners on appropriate use of Bayesian methods to address challenges in the rare disease setting.

Real-World Persistence and Treatment Patterns in Patients with Psoriatic Arthritis Treated with Anti-IL17 Therapy in Spain: The PerfIL-17 Study.

INTRODUCTION: Given the growing interest and use of interleukin-17 inhibitors (anti-IL17) for the treatment of psoriatic arthritis (PsA), an observational study has been conducted to characterize the patient profile, treatment patterns, and persistence of ixekizumab or secukinumab in patients with PsA receiving them as first anti-IL17. METHODS: This is a multicenter retrospective study, conducted at eight Spanish hospitals where data from adult patients with PsA were collected from electronic medical records. Three cohorts of patients, initiating treatment with an anti-IL17 [secukinumab 150 mg (SECU150), secukinumab 300 mg (SECU300), or ixekizumab (IXE)] between January 2019 and March 2021, were included. Demographic and clinical patient characteristics, treatment patterns, and persistence were analyzed descriptively. Continuous data were presented as mean [standard deviation (SD)] and categorical variables as frequencies with percentages. Persistence rates at 3, 6, and 12 months were calculated. RESULTS: A total of 221 patients with PsA were included in the study [SECU150, 103 (46.6%); SECU300, 38 (17.2%); and IXE, 80 (36.2%)]. Treatment patterns differed by clinical characteristics: SECU150 was initiated more frequently in patients with moderate PsA and less peripheral joint involvement, while patients on SECU300 included those with a higher rate of enthesitis and active skin psoriasis, and patients on IXE showed a longer time since PsA diagnosis, more frequent comorbidities, joint involvement, and diagnosed skin psoriasis. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) were previously administered in 88.2% of patients and biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) were administered in 72.9%. The mean number of previous b/tsDMARDs was 2.4 (SD 1.5) in the IXE cohort, 1.7 (SD 0.9) in the SECU300 cohort, and 1.6 (SD 1.0) for those in the SECU150 cohort. The global persistence on all anti-IL17 was 97.2%, 88.4%, and 81.0% at 3, 6, and 12 months, respectively. The most frequent reason for discontinuation across the three cohorts was lack of effectiveness (16.7%; 37/221). CONCLUSIONS: Most of the patients with PsA treated with anti-IL17 in Spain had moderate to severe disease activity, high peripheral joint and skin involvement, and had received previous b/tsDMARDs. More than 80% of patients with a 1-year follow-up persisted on anti-IL17, with the highest rate observed in the IXE cohort, followed by the SECU150 then SECU300 cohorts.

Use of Real-World Evidence for Drug Regulatory Decisions in China: Current Status and Future Directions.

Real-world data (RWD) and real-world evidence (RWE) have garnered great interest for supporting drug research and development (R&D) by medical researchers and regulators in recent years. The application and development of RWD/E in drug regulatory decision-making have been vigorously promoted in China. This study seeks to provide a broad overview of how RWE has been contributing to drug regulatory decisions in China. In this paper, we review the development of RWD and RWE, summarize key elements that promote application of RWE, introduce relevant methods and guidelines, elaborate on the opportunities and challenges of RWE in regulatory decision-making in China, and put forward suggestions to promote the application of RWE in China's regulatory decision-making and to further facilitate innovative drug evaluation and regulation.

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

BACKGROUND: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH risk stratification. METHODS: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: results from a real-world US cohort.

Introduction: Ixekizumab has demonstrated efficacy in pivotal trials in patients with psoriatic arthritis (PsA), both those naïve to prior biologic therapy and those with prior inadequate response or intolerance to biologics; however, minimal information is currently available on the effectiveness of ixekizumab in routine clinical practice. The objective of this study was to investigate the clinical effectiveness of ixekizumab for the treatment of PsA over 6- and 12-month follow-up periods in a real-world setting. Methods: This retrospective cohort study included patients who initiated treatment with ixekizumab from the OM1 PremiOMTM PsA dataset, a dataset of over 50,000 patients with claims and electronic medical record (EMR) data. Changes in musculoskeletal outcomes, such as tender and swollen joint count and patient-reported pain, as well as physician and patient global assessment, as measured using the Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) were summarized at 6 and 12 months. The RAPID3, CDAI score, and their individual components were assessed in multivariable regressions adjusting for age, sex, and baseline value. The results were stratified by biologic disease-modifying antirheumatic drug (bDMARD) status (naïve vs. experienced) and monotherapy status (monotherapy vs. combination therapy with conventional synthetic DMARDs). Changes in a 3-item composite score derived from a physician global assessment, patient global assessment, and patient-reported pain score were summarized. Results: Among the 1,812 patients identified receiving ixekizumab, 84% had prior bDMARD treatment and 82% were monotherapy users. All outcomes improved at 6 and 12 months. For RAPID3, the mean (SD) change at 6 and 12 months was -1.2 (5.5) and -1.2 (5.9), respectively. Patients overall, bDMARD experienced, and monotherapy patients achieved statistically significant mean change in CDAI and all components from baseline to 6 and 12 months in adjusted analyses. Patients experienced an improvement in the 3-item composite score at both time points. Conclusion: Treatment with ixekizumab was associated with improvements in musculoskeletal disease activity and PROs as assessed by several outcome measures. Future research should assess ixekizumab's clinical effectiveness in the real world across all PsA domains using PsA-specific endpoints.

Psychedelic therapy in the treatment of addiction: the past, present and future.

Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.