Objective The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD). Methods A keyword-based literature search was conducted, and 26 publications were included. Results Overall, 7–31% of patients had LN at SLE diagnosis; 31–48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40–76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3–11% and 6–19%, respectively, in patients with SLE and LN. Conclusions Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.

Connected drug delivery devices are increasingly being developed to support patient supervision and counseling in home setting. Features may include dosing reminders, adherence trackers, tools for patient education, and patient diaries to collect patient-reported outcomes, as well as monitoring tools with interfaces between patients and health care professionals (HCPs). Five connected devices have been selected as the basis for a review of the clinical evidence concerning the impact of electronic tools on treatment adherence and efficacy outcomes. Disease areas covered include multiple sclerosis, diabetes, hypertension, liver and renal transplant recipients, tuberculosis, hepatitis C, clinically isolated syndrome, asthma, and COPD. From studies comparing the use of electronic feedback tools to standard of care, there is an initial evidence for a higher adherence to treatment and better outcomes among patients who use the electronic tools. To substantiate the assumption that connected devices can improve adherence in an outpatient setting over a prolonged period of time, further data from controlled randomized studies are required. Key barriers to the broader adoption of connected devices include data privacy laws that may prevent data sharing with HCPs in some countries, as well as the need to demonstrate that the tools are consistently used and generate a high-quality and reproducible database. If these challenges can be addressed in a way that is agreeable to all stakeholders, it is expected that the future value of connected devices will be to 1) facilitate and improve patient involvement in disease management in a flexible care setting, 2) enable early treatment decisions, and 3) complement value-based reimbursement models.

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Introduction Numerous medications are used for the preventive treatment of chronic migraine (CM), including oral treatments, onabotulinumtoxinA (onabotA; BOTOX), and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). Despite substantial clinical trial evidence, less is published about the real-world experience of these treatments based on data routinely collected from a variety of sources. This systematic review assessed real-world evidence on the effectiveness and safety of preventive treatments for CM in adults. Methods A systematic search of MEDLINE, Embase, and the Cochrane library with back-referencing and supplementary searches retrieved data published between January 2010 and February 2020. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. Search criteria included preventive medications for CM. Evidence was available for topiramate, onabotulinumtoxinA, CGRP mAbs (erenumab, galcanezumab, and fremanezumab). OnabotulinumtoxinA was most commonly assessed (55 studies), followed by erenumab (six studies), multiple CGRP mAbs (one study), and topiramate (one study). Long-term data (> 1 year) were available for onabotulinumtoxinA only, with erenumab reported up 6 months, topiramate up to 3 months, and multiple CGRP mAbs up to 12 months. Results Substantial data demonstrated that onabotulinumtoxinA reduces the number/frequency of headaches, concomitant acute medication use, and impact of headaches on well-being and daily activity. More limited evidence showed benefits for the same parameters with erenumab. Single studies suggested topiramate and multiple CGRP mAbs decrease the number/frequency of headaches and impact of headaches. To date, onabotulinumtoxinA is the only preventive treatment for CM that has long-term safety data in real-world settings reporting treatment-related adverse events of up to 3 years. Conclusion While substantial real-world evidence supports the long-term effectiveness and safety of onabotulinumtoxinA, real-world data on other preventive treatments of CM are currently limited to short term effectiveness due to their more recent approvals. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-022-00452-3.

Background Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by abnormal B-cell activation and the presence of autoantibodies, which can result in organ damage. Lupus nephritis (LN) is the most common severe organ manifestation of SLE and may result in impaired kidney function. However, there is limited research on the health-related quality of life (HRQoL) burden amongst patients with LN. The objective of this systematic literature review was to assess the HRQoL, fatigue and health utilities associated with LN. Methods A structured literature search (GSK Study 212980) of the MEDLINE and Embase databases was conducted in July 2019 and updated September 2021. Relevant international congress abstracts from 2016 to 2021 were searched, and gray literature searches and keyword-based searches in PubMed, Google, and Google Scholar were also conducted. Results were screened according to predefined criteria and data on the outcomes of interest were extracted. A quantitative analysis was conducted to supplement the narrative review, to provide 36-item Short Form survey (SF-36) estimates, and to determine variation by prognostic factors. Results Of 1155 articles identified, 26 studies for a total of 3440 patients were included. Patients with LN showed poorer HRQoL and more fatigue than healthy controls/the general population, although these were similar between patients with SLE with and without LN. HRQoL was worse in patients with LN Class III/IV or with active disease. Fatigue was generally reported as the most burdensome symptom and was associated with lower HRQoL and increased treatment dissatisfaction. During induction treatment, HRQoL and fatigue were improved with mycophenolate mofetil versus cyclophosphamide. HRQoL improved over time with treatment amongst patients with active LN. Very limited data were identified assigning utilities to health states for cost-effectiveness analysis. Nine studies were considered for quantitative analysis of baseline SF-36 scores. The analysis suggested that LN has a significant impact across all SF-36 domains, with the lowest scores in the general health perceptions and role-physical domains and physical component summary. Conclusions There is a large HRQoL burden in patients with LN, in particular regarding symptoms of fatigue. Future research should focus on investigating fatigue severity and health utilities in LN.

Background Digital therapeutics (DTx) are software-based products that prevent, manage, or treat a medical condition and are delivered through a smartphone app, web application, or wearable device. Clinical trials assessing DTx pose challenges, foremost among which is designing appropriate digital shams (or digital placebos), which should ideally mimic DTx (in terms of design, components, and duration of treatment) while omitting the active principle or component. Objective The objective of our review was to understand how digital shams are being used in clinical research on DTx in neuroscience, which is the most common therapy area for DTx. Methods We conducted a systematic literature review of DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) with a focus on controlled clinical trials involving digital shams. Studies were identified from trial registries (ClinicalTrials.gov, the European Union Clinical Trials Register, and Trial Trove) and through structured searches in MEDLINE and Embase (both via the Embase website) and were limited to articles in English published from 2010 onward. These were supplemented by keyword-based searches in PubMed, Google, and Google Scholar and bibliographic searches. Studies assessing DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) were included. Details related to the publication, DTx, comparator, patient population, and outcomes were extracted and analyzed. Results Our search criteria identified 461 neuroscience studies involving 213 unique DTx. Most DTx were extended reality based (86/213, 40.4%) or mobile device based (56/213, 26.3%); 313 were comparative, of which 68 (21.7%) used shams. The most common therapeutic areas assessed in these studies were stroke (42/213, 19.7%), depression (32/213, 15%), and anxiety (24/213, 11.3%). The most common treatments were cognitive behavioral therapy or behavioral therapy (67/213, 32.4%), physical rehabilitation (60/213, 28.2%), and cognitive training (41/213, 19.2%). We identified the following important issues related to the use of digital shams in neuroscience: shams were not validated before use in studies, they varied widely in design (from being nearly identical to the DTx to using different software programs altogether), and the level of patient engagement or satisfaction with the sham and the impact of the sham on study outcomes were infrequently reported. Conclusions Digital shams are critical for the clinical development of DTx in neuroscience. Given the importance of sham controls in evaluating DTx efficacy, we provide recommendations on the key information that should be reported in a well-designed DTx trial and propose an algorithm to allow the correct interpretation of DTx study results. Sham-controlled studies should be routinely used in DTx trials—in early-phase studies—to help identify DTx active components and—in late-phase studies—to confirm the efficacy of DTx. The use of shams early in development will ensure that the appropriate sham control is used in later confirmatory trials.

UNSTRUCTURED Digital therapeutics (DTx) are software-based products that prevent, manage, or treat a medical condition, and are delivered through a smartphone app, web application or wearable. Clinical trials assessing DTx pose challenges, foremost amongst which is designing appropriate ‘digital shams’ (or ‘digital placebos’), which should ideally mimic the DTx (in terms of design, components and duration of treatment) while omitting the active principle/component. To understand how digital shams are being used in clinical research on DTx, we conducted a systematic literature review (SLR) of DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) with a focus on controlled clinical trials involving digital shams. Our search criteria identified 461 neuroscience studies involving 213 unique DTx. Most DTx were extended reality-based (40.4%) or mobile device-based (26.3%); 313 were comparative, of which 68 used shams. The most common therapeutic areas assessed in these studies were stroke (19.7%), depression (15%) and anxiety (11.3%); and the most common treatments were cognitive behavioral therapy/behavioral therapy (32.4%), physical rehabilitation (28.2%), and cognitive training (19.2%). Results: We identified the following important issues related to the use of digital shams: shams were not validated prior to use in studies; they varied widely in design; (from being near-identical to the DTx to using different software programs altogether); the level of patient engagement/satisfaction with the sham and the impact of the sham on study outcomes was infrequently reported. Conclusions: Digital shams are critical to the clinical development of DTx. Given the importance of sham controls in evaluating DTx efficacy, we provide recommendations on the key information that should be reported in a well-designed DTx trial and propose an algorithm to allow correct interpretation of DTx study results. Sham-controlled studies should be routinely used in DTx trials – in early phase studies, to help identify DTx active components, and in late-phase studies, to confirm the efficacy of DTx. Use of shams early in development will ensure that the appropriate sham control is used in later confirmatory trials.

BackgroundDespite recent advances in the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN), understanding of their pathogenesis and the interrelation between disease states remains incomplete. A pragmatic review (GSK study LS3178) was conducted to map disease severity and progression of renal involvement in SLE, focusing on: LN development among patients with SLE, within-LN progression, and progression to end-stage renal disease (ESRD).MethodsA keyword based literature search was conducted using PubMed, Google and Google Scholar and supplemented with a bibliography search relevant to the focus area. The following publications were screened and prioritized for inclusion: high quality; published after 2010; addressed a topic of focus or an information gap; data were from the USA or Europe. High-quality pre-2010 and non-USA/Europe publications were permitted.ResultsOverall, 248 citations were identified (keyword based search, n=117; bibliography search, n=131). Following full text screening, 144 publications were considered relevant to the review and 26 were selected for inclusion (21 primary studies, 3 narrative reviews and 2 systematic literature reviews). An overview of the results is provided in the Figure. This review identified that 726% of patients had LN at the time of SLE diagnosis, and 3148% of patients with SLE developed LN in the disease course, most (8090%) within 5 years of diagnosis. Class IV nephritis was the most common LN class found at first (3560%) and repeat (3563%) biopsy and had the worst prognosis. Histological transformation from one LN class to another was reported in 4076% of patients, most commonly in patients with nonproliferative lesions in the first biopsy. Overall, the proportion of patients who subsequently developed ESRD was 36% (SLE) and 428% (LN). Limited data existed for time to progression within LN and from SLE/LN to ESRD, and for renal signs present before LN diagnosis.Abstract 87 Figure 1ConclusionsThis review highlights risk factors for developing LN and progressing from SLE/LN to ESRD. Male patients, patients of non white ethnicities, and patients of a younger age at SLE diagnosis had the highest risk for developing LN and progressing from SLE/LN to ESRD. Of the renal parameters, elevated serum creatinine was identified as the best predictor of worsening disease state. A higher risk of worse outcomes is seen in the earlier SLE/LN disease stages, demonstrating the importance of early diagnosis and the need for effective disease modifying treatments for SLE and LN.Funding Source(s):Study funded by GSK.