Real-world Patients Research Articles

Single-microglia transcriptomic transition network-based prediction and real-world patient data validation identifies ketorolac as a repurposable drug for Alzheimer's disease.

High microglial heterogeneities hinder the development of microglia-targeted treatment for Alzheimer's disease (AD). We integrated 0.7 million single-nuclei RNA-sequencing transcriptomes from human brains using a variational autoencoder. We predicted AD-relevant microglial subtype-specific transition networks for disease-associated microglia (DAM), tau microglia, and neuroinflammation-like microglia (NIM). We prioritized drugs by specifically targeting microglia-specific transition networks and validated drugs using two independent real-world patient databases. We identified putative AD molecular drivers (e.g., SYK, CTSB, and INPP5D) in transition networks of DAM and NIM. Via specifically targeting NIM, we identified that usage of ketorolac was associated with reduced AD incidence in both MarketScan (hazard ratio [HR]=0.89) and INSIGHT (HR=0.83) Clinical Research Network databases, mechanistically supported by ketorolac-treated transcriptomic data from AD patient induced pluripotent stem cell-derived microglia. This study offers insights into the pathobiology of AD-relevant microglial subtypes and identifies ketorolac as a potential anti-inflammatory treatment for AD. An integrative analysis of≈ 0.7 million single-nuclei RNA-sequencing transcriptomes from human brains identified Alzheimer's disease (AD)-relevant microglia subtypes. Network-based analysis identified putative molecular drivers (e.g., SYK, CTSB, INPP5D) of transition networks between disease-associated microglia (DAM) and neuroinflammation-like microglia (NIM). Via network-based prediction and population-based validation, we identified that usage of ketorolac (a US Food and Drug Administration-approved anti-inflammatory medicine) was associated with reduced AD incidence in two independent patient databases. Mechanistic observation showed that ketorolac treatment downregulated the Type-I interferon signaling in patient induced pluripotent stem cell-derived microglia, mechanistically supporting its protective effects in real-world patient databases.

Older adults’ recognition of medical terminology in hospital noise

Word identification accuracy is modulated by many factors including linguistic characteristics of words (frequent vs. infrequent), listening environment (noisy vs. quiet), and listener-related differences (older vs. younger). Nearly, all studies investigating these factors use high-familiarity words and noise signals that are either energetic maskers (e.g., white noise) or informational maskers composed of competing talkers (e.g., multitalker babble). Here, we expand on these findings by examining younger and older listeners’ speech-in-noise perception for words varying in both frequency and familiarity within a simulated hospital noise that has important non-speech information. The method was inspired by the real-world challenges aging patients can face in understanding less familiar medical terminology used by healthcare professionals in noisy hospital environments. Word familiarity data from older and young adults were collected for 800 medically related terms. Familiarity ratings were highly correlated between the two age groups. Older adults’ transcription accuracy for sentences with medical terminology that vary in their familiarity and frequency was assessed across four listening conditions: hospital noise, speech-shaped noise, amplitude-modulated speech-shaped noise, and quiet. Listeners were less accurate in noise conditions than in a quiet condition and were more impacted by hospital noise than either speech-shaped noise. Sentences with low-familiarity and low-frequency medical words combined with hospital noise were particularly detrimental for older adults compared to younger adults. The results impact our theoretical understanding of speech perception in noise and highlight real-world consequences of older adults’ difficulties with speech-in-noise and specifically noise containing competing, non-speech information.

Prognostic Impact of Patient-Reported Symptoms in Multiple Myeloma.

Patient-reported outcomes (PROs) are associated with treatment outcomes in multiple myeloma (MM) in the clinical trial setting. However, most PRO tools are time consuming, which hinders use in routine practice. Our institution incorporated a "Hematology Patient-Reported Symptom Screen" (HPRSS), a 3-item questionnaire for fatigue, pain, and quality of life (QOL). The main objective of this study was to evaluate the impact of these symptoms on progression-free (PFS) and overall survival (OS) in real-world cohort patients with newly diagnosed MM. This retrospective study included MM patients diagnosed between April 2011-December 2017, seen at Mayo Clinic (Rochester MN), who completed the HPRSS. Patients rated their symptoms on a scale from 0-10. Clinically relevant symptoms were defined as scores ≥5 for pain and fatigue, and ≤5 for QOL. At diagnosis, 735 patients had scores for all domains. The median follow-up was 8.1 years. Age was associated with increased odds of fatigue and decreased QOL. Female sex and comorbidities were associated with fatigue and pain. Higher disease stage, anemia, lytic lesions, and plasma cell burden were associated with fatigue, pain, and decreased QOL. Clinically relevant fatigue, pain, and decreased QOL were associated with decreased PFS and OS. On multivariate analysis including age, ISS III, high-risk cytogenetics, and post-induction transplantation, fatigue and decreased QOL were independently associated with decreased OS. A composite HPRSS score stratified patients into three groups with distinct OS. Patient-reported symptoms are prognostic in newly diagnosed MM patients. The prognostic values of fatigue and QOL are independent of age, stage, and transplant.

Comparison of On-Label Treatment Persistence in Real-World Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Interleukin-17A Inhibitors.

Psoriatic arthritis (PsA) is a chronic, multidomain, inflammatory disease requiring long-term treatment. Guselkumab, a fully human interleukin [IL]-23p19-subunit inhibitor, and the IL-17A inhibitors (IL-17Ai) ixekizumab and secukinumab are approved by the US Food and Drug Administration (FDA) for adults with active PsA. Real-world data evaluating on-label treatment persistence is an important consideration for patients. This retrospective claim-based analysis (IQVIA PharMetrics® Plus) included adults with PsA receiving guselkumab or their first subcutaneous (SC) IL-17Ai (ixekizumab/secukinumab) per FDA label ("on-label") between July 14, 2020, and June 30, 2022. Baseline demographicanddisease characteristics were collected in the 12 months preceding the index date (date of first guselkumab or SC IL-17Ai claim); follow-up extended through the earlier of theend of continuous insurance eligibility or end of data availability. Baseline characteristics were balanced between the cohorts by propensity score weighting (standardized mortality ratio [SMR]). Discontinuation was defined as a gap 2 × the FDA-approved maintenance dosing interval (guselkumab:112 days; SC IL-17Ai: 56 days); on-label persistence in the weighted cohorts was assessed using Kaplan-Meier curves and compared with a Cox proportional hazards model. Weighted demographic and disease characteristics were well balanced between the cohorts (guselkumab: N = 910, mean age = 50.4 years, 60.4% female; SC IL-17Ai: N = 2740, mean age = 50.2, 59.4% female). At 12 months, the guselkumab cohort was 1.85 × more likely to remain persistent with on-label therapy vs the SC IL-17Ai cohort (p < 0.001); median time to discontinuation was not reached for guselkumab and was12.3 months for SC IL-17Ai. At 3, 6, 9, and 12 months, persistence rates in the weighted cohorts were higher with guselkumab than with SC IL-17Ai (p < 0.001). In this real-world claims data analysis in adults with PsA, on-label persistence rates were statistically significantly higher with guselkumab, as early as 3 months, with ~ 2 × greater likelihood of persistence at 12 months relative to SC IL-17Ai.

Real-World Safety Profile of Direct Oral Anticoagulants (DOACs): Disproportionality Analysis of Major Bleeding Events

BackgroundDirect Oral Anticoagulants (DOACs) have revolutionized the management of thrombotic conditions, providing more predictable and manageable anticoagulation compared to traditional vitamin K antagonists. Despite their success, major bleeding events remain a significant concern. This study aims to assess and compare the haemorrhagic risks associated with various DOACs using data from the FDA's Adverse Event Reporting System (FAERS). MethodsA retrospective disproportionality analysis of the FAERS database was conducted, covering the period from January 1, 2015, to December 31, 2023. The study focused on adverse bleeding events reported for DOACs. The Proportional Reporting Ratio (PRR) was calculated for each DOAC to identify disproportionate reporting of haemorrhagic events. Major haemorrhagic events were classified as those leading to hospitalization. The analysis also utilized the Medicare Part D dataset to estimate the usage of specific DOACs from 2015 to 2021. ResultsA total of 353,188 haemorrhagic events were identified, with 17,236 (4.9%) attributed to DOACs. The PRR for major haemorrhagic events was highest for Edoxaban at 14.1 (95% CI 13.93-14.85), followed by Dabigatran at 4.0 (95% CI 3.81-4.20), Apixaban at 3.53 (95% CI 3.47-3.61), and Rivaroxaban at 2.11 (95% CI 2.05-2.18). Edoxaban also had the highest PRR for cerebral haemorrhages. Medicare data indicated that Apixaban was the most commonly used DOAC (58.3%), followed by Rivaroxaban (34.5%). ConclusionsEdoxaban shows a significantly higher risk of major and cerebral haemorrhages compared to other DOACs, while Rivaroxaban demonstrates a lower overall risk of haemorrhage. These findings emphasize the need for careful consideration of bleeding risks in DOAC therapy. Continuous post-marketing surveillance is crucial for understanding the safety profiles of DOACs in real-world clinical settings, aiding clinicians and patients in making informed decisions about anticoagulant therapy.

An optimal antibiotic selection framework for Sepsis patients using Artificial Intelligence

In this work we present OptAB, the first completely data-driven online-updateable antibiotic selection model based on Artificial Intelligence for Sepsis patients accounting for side-effects. OptAB performs an iterative optimal antibiotic selection for real-world Sepsis patients focussing on minimizing the Sepsis-related organ failure score (SOFA-Score) as treatment success while accounting for nephrotoxicity and hepatotoxicity as serious antibiotic side-effects. OptAB provides disease progression forecasts for (combinations of) the antibiotics Vancomycin, Ceftriaxone and Piperacillin/Tazobactam and learns realistic treatment influences on the SOFA-Score and the laboratory values creatinine, bilirubin total and alanine-transaminase indicating possible side-effects. OptAB is based on a hybrid neural network differential equation algorithm and can handle the special characteristics of patient data including irregular measurements, a large amount of missing values and time-dependent confounding. OptAB’s selected optimal antibiotics exhibit faster efficacy than the administered antibiotics.

Bridging the Research-to-Practice Gap: The Individual Placement and Support Model.

The Research-to-Practice Gap often hinders the translation of effective healthcare interventions from clinical trials to routine care. Individual Placement and Support (IPS), an evidence-based practice designed to help individuals with mental health conditions achieve and maintain employment, has notably bridged this gap. Unlike many interventions that struggle with widespread implementation, IPS has successfully scaled to over 2,000 programs across all U.S. states and 30 other countries. This paper examines the strategies that have facilitated the rapid and extensive adoption of IPS, offering insights into best practices for integrating randomized controlled trial (RCT) findings into everyday clinical settings. Key factors contributing to the success of IPS include conducting RCTs in settings with real-world patients and clinicians, fostering collaboration through the International IPS Learning Community, developing comprehensive implementation materials and a dynamic fidelity scale, and engaging in regular, systematic meetings with stakeholders such as providers, advocates, and policymakers. These approaches have ensured that IPS remains adaptable, responsive to patient needs, and maintains fidelity to its core principles while promoting continuous improvement. The experience with IPS underscores the importance of integrating real-world evidence with clinical practice through ongoing collaboration among all stakeholders. The principles underpinning IPS-real-world application, stakeholder engagement, and adaptability-provide a model that could guide future efforts to close the research-to-practice gap across diverse healthcare settings and interventions.

EGFR slope as predictor of mortality in heart failure patients.

Heart failure (HF) leads to an imbalance between heart and kidney function, resulting in poor outcomes. However, the prognostic significance of the estimated glomerular filtration rate (eGFR) trajectory in HF patients remains unclear. We analysed electronic health records (EHRs) of real-world HF patients, assessing eGFR trajectories and their impact on mortality. Retrospective clinical data of HF patients were processed using natural language processing. Chronic kidney disease (CKD) was evaluated, and eGFR trajectories were analysed using linear mixed-effects models. Cox proportional hazard models were used to evaluate the relationship between baseline variables and mortality, while joint modelling combined eGFR trends and mortality. The dataset comprised 1986 patients, with a mean age of 74.8years (SD±11.7) and 58% male. At the time of HF diagnosis, 58% of patients were diagnosed with CKD, and 39% presented with heart failure with preserved ejection fraction (HFpEF). The median follow-up duration was 3.16years, during which 399 patients (20%) died. Patients with CKD were significantly older and exhibited a higher prevalence of myocardial infarction (P=0.048), coronary revascularization (P=0.004), stroke (P<0.001), atrial fibrillation (P<0.001) and type 2 diabetes (P<0.001). Mortality rates at 1 and 2years were nearly twice as high in CKD patients compared with those without (P<0.001). Notably, CKD was significantly less prevalent among survivors (55% vs. 71%, P<0.001). Key predictors of mortality included older age, beta-blocker use, prior stroke, lower serum haemoglobin levels, and elevated potassium and NT-proBNP levels. Each 10mL/min/1.73m2 decrease in eGFR was associated with a 1.22 (95% CI: 1.10-1.35, P<0.001) increase in mortality hazard. Additionally, a 1-year decline of 10mL/min/1.73m2 in eGFR resulted in a mortality hazard of 1.97 (95% CI: 1.45-2.69, P<0.001). CKD is prevalent in a real-world HF population and is an independent predictor of mortality. The current eGFR value and the eGFR slope from the previous year have the potential to be used for assessing individual mortality risk in the clinical follow-up of HF patients.

Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature

Purpose: Single-agent immune checkpoint inhibitor (IO) therapy is the standard for non-oncogene-addicted advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score ≥ 50%. Smoking-induced harm generates high tumor mutation burden (H-TMB) in smoking patients (S-pts), while never-smoking patients (NS-pts) typically have low TMB (L-TMB) and are unresponsive to IO. However, the molecular characterization of NS-pts with H-TMB remains unclear. Experimental design: Clinical data of 142 aNSCLC patients with PD-L1 ≥ 50% treated with first line pembrolizumab were retrospectively collected. Next-generation sequencing was performed using the FoundationOne®CDx assay to correlate genomic alterations with clinical characteristics and response outcomes. Detected mutations were classified into eleven main pathways and enrichment analysis identified patient subgroups based on mutated pathways. Additionally, a patient similarity network was constructed to analyze molecular characterization. Results were validated using data from 853 aNSCLC patients in POPLAR and OAK trials. Results: Among the patients, S-pts had higher TMB than NS-pts. Interestingly, 11 (8%) NS-pts exhibited H-TMB and were enriched in β-catenin/Wnt and DDR pathway mutations. DDR pathway mutations were confirmed to be enriched in NS-pts with H-TMB using data from POPLAR and OAK trials. In the real-world cohort, the NS/H-TMB subgroup with DDR pathway mutations demonstrated improved IO outcome. Patient similarity network analysis confirmed the clustering of NS/H-TMB patients with DDR mutations and their association with improved overall survival in both the real-world cohort and the trials. Conclusions: The DDR signature has a potential role as an additional generator of H-TMB in NS-pts. This subgroup of IO-responsive NS-pts may have better prognosis. Our findings suggest that DDR-based mutational profiling may help identify NS-pts who could benefit from IO therapy.

Prospective cohort study of basivertebral nerve ablation for chronic low back pain in a real-world setting: 12 months follow-up

BackgroundThe basivertebral nerve, which densely supplies the vertebral endplates, is a potential source of chronic low back pain transmission in patients with Modic changes. Basivertebral nerve ablation (BVNA), a minimally invasive procedure, aims to disrupt this pain signaling. ObjectivesIn this study, we investigated BVNA's effectiveness in treatment of vertebrogenic low back pain and we followed patients for 12 months to assess long-term effectiveness. Study designSingle group prospective cohort study (ClinicalTrials.gov NCT05692440). SettingSingle-center, community private practice. MethodsThirty-five patients were treated with the INTRACEPT® device (Boston Scientific, MA, USA). Thirty-one patients completed Oswestry Disability Index (ODI), Visual Analog Scale (VAS), SF-36 Physical Component Summary (PCS), and SF-36 Mental Component Summary (MCS) at baseline and follow-up visits up to 12 months. ResultsThe average age of the 31 patients was 73.0 ± 6.34 years and 71.0 % of the population was male (N=22)) at baseline. All four self-reported outcomes (ODI, VAS, SF-36 PCS, and MCS) showed statistically and clinically significant improvements from baseline through 12 months (all p < 0.001, with the exception of the SF-36 MCS at 1 month, p = 0.165). Overall, 67.7 % of patients demonstrated ODI improvements above the minimal clinically important difference (decrease of at least 15 points) and 77.4 % of patients demonstrated a decrease on the VAS above the minimal clinically important difference (≥2 cm reduction) at 12 months. LimitationsLimitations of the study include the lack of a control group and potentially unintentional bias in patient selection. ConclusionsBVNA demonstrates potential as an effective and minimally invasive treatment for chronic low back pain in a real-world patient cohort where substantial improvements were observed. These results align with those seen in previous randomized controlled trials (RCTs) and industry-funded studies of BVNA.

Investigation of Severe Hypoglycemia Risk Among Patients with Diabetes Treated with Ultra-Rapid Lispro in Japan.

There is no information on the incidence of severe hypoglycemia in real-world patients with diabetes receiving ultra-rapid lispro (URLi). This post-marketing, observational, safety study assessed the incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit in URLi-treated patients. It also compared the risk of severe hypoglycemia between patients treated with URLi or other rapid-acting insulin analogs (RAIAs). Claims data were obtained from a nationwide hospital-based administrative database in Japan (Medical Data Vision). Adults with diabetes who initiated URLi or other RAIA on/after June 01, 2020, were followed up through May 31, 2023. Severe hypoglycemia was identified using a validated algorithm. Incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit was described in URLi-treated patients (descriptive analysis). These outcomes were also compared against propensity score (PS)-matched other RAIA-treated patients (comparator; comparative analysis). Hazard ratio (HR) and 95% confidence interval (CI) was estimated with a Cox proportional hazards model. The descriptive analysis' URLi-treated cohort included 17,838 patients [mean (standard deviation, SD) age 65.9 (15.7) years; 58.3% male]. The majority had type 2 diabetes (75.7%). The incidence proportion of the first severe hypoglycemia event requiring a hospital visit was 0.6% (95% CI 0.5, 0.8) and the incidence rate was 1.7 per 100 person-years (95% CI 0.7, 4.3). The comparative analysis included 10,592 URLi-treated and 52,917 comparator-treated patients. The incidence rate of severe hypoglycemia did not significantly differ between these cohorts (HR 0.8; 95% CI 0.5, 1.1; p=0.132;. This study did not show a statistically significant increase in the incidence and risk of the first severe hypoglycemia event requiring a hospital visit in real-world URLi-treated patients in Japan, compared with a PS-matched cohort of other RAIA-treated patients.

Adaptive dosing of high-dose busulfan in real-world adult patients undergoing haematopoietic cell transplant conditioning.

To evaluate the effectiveness of a Bayesian adaptive dosing strategy in achieving target busulfan exposure in adult patients undergoing haematopoietic cell transplantation (HCT). This study included 71 adult patients scheduled to receive high-dose busulfan. Busulfan was administered to achieve a cumulative area under the curve (AUC) of 66.0mg/L/h (16 000 μM/min), 82.60 mg/L/h (20 000 μM/min) or 87.6mg/L/h (21 200 μM/min) depending on the regimen. Individual pharmacokinetic (PK) parameters of busulfan were estimated from three blood samples using a one-compartment model and Bayesian estimation after the first standard dose. Individual PK parameters were used to adjust subsequent doses to achieve the target exposure. All patients had their dose adjusted after the first dose administration. The final deviation from the target AUC was significantly improved compared to the initial deviation after standard mg/kg dosing (mean absolute deviation 19.5% vs 11.7%, P< .01). In addition, the proportion of patients with marked deviation from target exposure (ie, >25%) decreased significantly from 31% after standard dosing to 10% after PK-guided dosing (P< .01). Canonical busulfan-related toxicity, specifically veno-occlusive disease, was observed in 5% of patients who achieved successful PK-guided dosing. In contrast, one-third of patients with off-target exposure with poor dosing experienced toxicity. The Bayesian adaptive dosing strategy significantly improves the accuracy of achieving the target busulfan AUC in patients undergoing HCT. This approach not only reduces marked deviations from target exposure, but also reduces the incidence of busulfan-related toxicity, thereby maintaining a favourable toxicity/efficacy ratio.

Towards a Further Understanding of Meta-Analysis Using Gestational Exposure to Cannabis and Birth Defects as a Case in Point.

About 5%-10% of pregnancies in the US are exposed to cannabis with highest use reported during the first trimester. Two recent meta-analyses presented estimates of the risk of birth defects associated with prenatal exposure to cannabis; the larger and more recent meta-analysis pooled data from 18 cohort and 18 case-control studies with a total sample size of >19 million subjects. The meta-analyses found that prenatal exposure to cannabis was associated with a small but statistically significant increased risk of any birth defect (pooled odds ratios [ORs], 1.25-1.33); ORs were also significantly elevated for cardiovascular, gastrointestinal, nervous system, genitourinary, and musculoskeletal but not orofacial birth defects. The ORs were smaller and less likely to be statistically significant in adjusted analyses. These meta-analyses had strengths but also shortcomings. The strengths and shortcomings are explained in detail so that readers obtain a better understanding of how to critically assess findings in meta-analyses. One strength was the presentation of both unadjusted and adjusted pooled estimates; the former allow an understanding of risks in the average real world patient and the latter allow an understanding of the unique contribution of the exposure to the outcomes. Another strength was the presentation of cumulative meta-analyses which demonstrated from which calendar year onwards a finding became consistently statistically significant in the scientific literature. One shortcoming, in analyses of subcategories of birth defects, was the repeated representation of the same sample in the same forest plot; the many reasons why this is problematic are explained. Another shortcoming was the pooling of ORs obtained from cohort studies with those obtained from case control studies; conceptual and numerical reasons why this is problematic are also explained.

Retrospective Analysis of the Impact of Screening for Psoriatic Arthritis (PsA) with the Psoriasis Epidemiology Screening Tool (PEST) in Clinical Dermatology Practice

Introduction: Patients with plaque psoriasis (PSO) have an increased risk of developing PsA as the disease severity progresses. While it is estimated that 30% of patients with PSO have PsA, nearly 16% of patients with PSO may have undiagnosed PsA.1,2 Implementing the PEST questionnaire for PsA screening in dermatologic practice may increase early intervention by improving rates of timely diagnosis.3 This observational study aimed to assess the proportion of patients with PSO and no previous PsA diagnosis who screened positive on the PEST and were then diagnosed with PsA by a healthcare provider in the PEST deployment period within the Advanced Dermatology and Cosmetic Surgery (ADCS) specialty dermatology network. Procedure/Study: De-identified, real-world patient data [2018–2019 and 2021–2022] were sourced from electronic health records within the ADCS network of outpatient facilities across 14 states in the United States. Patients were included in the analysis if they received care at an ADCS facility where the PEST was deployed, had ≥1 encounter with a diagnosis code for PSO, and never had a diagnosis code for PsA before their first diagnosis code for PSO. For outcomes directly related to PEST evaluations, data from 1/1/2021–12/31/2022 (PEST deployment period) were used. For outcomes not directly related to PEST results, data from 1/1/2018–12/31/2019 (period before PEST deployment) were evaluated. Descriptive statistics, including frequencies, percentages, and 95% confidence intervals (CIs) for categorical variables, were used to characterize the patient cohorts by study period. Results: Among ADCS facilities using the PEST during the deployment period (44% of practices in the network), the final study population included 14,308 and 21,142 patients with PSO in the period before PEST deployment and during the PEST deployment period, respectively. In the PEST deployment cohort, 1,100 (5.2%; 95% CI: 4.9–5.5) patients were screened using the PEST. In the period before PEST deployment, 327 (2.3%; 95% CI: 2.0–2.5) patients with PSO and no previous PsA diagnosis were subsequently diagnosed with PsA. During the PEST deployment period, 449 (2.1%; 95% CI: 1.9–2.3) patients with PSO and no previous PsA diagnosis received a subsequent PsA diagnosis without PEST screening. Of all patients with PSO who screened positive for PsA on the PEST (score ≥3; n=296), 10.8% (n=32; 95% CI: 7.6–15.1) subsequently received a formal PsA diagnosis during the PEST deployment period. Conclusion: These results suggest that a meaningful proportion of patients with PsA may be underdiagnosed in the dermatology setting. Deployment of the PEST in the clinical dermatologic workflow may provide an opportunity to diagnose PsA earlier and improve patient outcomes.

Worldwide Clinical and Real-World Exposure to Baricitinib

Introduction: Baricitinib (BARI), an oral selective JAK inhibitor, is approved in many geographies for adults with rheumatoid arthritis or alopecia areata and for patients as young as age 2 years with atopic dermatitis or juvenile idiopathic arthritis. It is also approved in the US for hospitalized patients with COVID-19 infection. We report the worldwide clinical trial and real-world exposure to BARI across a range of diseases, ages and racial backgrounds. Methods: Real-world patient exposure estimates were calculated based on total mg sold, average daily dose, and average length of therapy as reported to regulatory agencies through the cumulative timeframe ending Jan. 31, 2024. Clinical trial exposures were based on actual exposures from completed trials through Feb. 13, 2024, and estimates were made for ongoing blinded trials based on the enrolment/randomization schemes Results: In the real-world setting, an estimated 1,836,600 patients have been exposed to the following BARI doses: 1 mg, ~2,000 (0.1%); 2 mg, ~524,900 (28.6%); 4 mg, ~1,309,600 (71.3%). Of these estimated exposures, ~ 57% were for COVID-19 with the remaining for all other indications combined. Across 59 clinical trials (completed and ongoing), an estimated 14,660 subjects (548 healthy volunteers and 14,112 patients) have received BARI since June 2008. Exposures from completed studies include 10,276 patients (62% female), 399 of whom were &lt;18 yrs of age (≤1 month, N=4; 1 month - ≤2 yrs, N=24; &gt;2 - ≤12 yrs, N=111; &gt;12 - ≤18 yrs, N=260), 8820 were &gt;18 to ≤65 yrs, 1027 were &gt;65 yrs, and 30 had age unknown. An additional 467 adolescent and pediatric patients down to the age of 2 have been treated with BARI for atopic dermatitis in an ongoing clinical trial, bringing the total number of patients &lt;18 years of age to 866 across dermatologic, rheumatologic, other autoimmunologic, and acute infectious diseases (excluding alopecia areata for which there is an ongoing pediatric trial). Clinical trial exposures by racial and ethnic background are as follows: Asian, N=2,491; Black, N=450; Caucasian, N=6,237; other, N=496; multiple, N=135; unknown, N=467. Conclusion: There has been extensive real-world exposure to BARI across indications and populations, and BARI is a well-studied molecule in clinical trials, across varied disease states, racial populations and ages. Since average daily dose and length of therapy may vary over time, real-world exposures are only an estimate of total patients receiving BARI. Exposures in clinical trials include patients as young as less than 1 month of age up to patients over the age of 65 years. While these exposures do not indicate efficacy or safety, they provide data to establish the overall profile of the drug and can inform on its performance over time across a variety of populations.

Provider Burden Associated With Apremilast Adverse Events

Introduction: In December 2021, the US Food and Drug Administration (FDA) expanded its initial approval for apremilast to include moderate and severe cases of psoriasis. However, real-world epidemiology data regarding the use of apremilast, the influence of adverse events (AEs), and the burden of AEs on managing physicians, has been lacking. This retrospective, observational, multisite study aimed to describe real-world patient characteristics, AEs (including diarrhea, nausea, and headache), and healthcare provider-level burden associated with the psoriasis treatment apremilast in the US. Methods: Dermatologists abstracted medical record data for adults treated with apremilast on or after January 1, 2018, who had ≥3 months of data available. Dermatologist and patient characteristics, including demographics and clinical characteristics, AEs, and provider burden in managing AEs were summarized using descriptive statistics. Results: Forty-seven dermatologists nationwide responded to a survey and conducted a chart review of 308 patients. Dermatologists practiced in various US geographic regions. The most common practice setting was in a private community with 2 to 5 physicians (34.0%). Most patients were White (74.4%), non-Hispanic (86.0%), and male (55.2%). The mean age at diagnosis was 43.6 years (SD, 16.8 years). AEs occurred in 29.2% of patients, with the most common being diarrhea (16.2%), followed by nausea (13.6%) and headache (4.9%). Diarrhea mostly occurred ≤30 days into treatment (87.2%) and resulted in 1 additional office visit (39.5%) and 3 phone calls per patient to their providers (34.9%). Nausea mostly occurred within 30 days (70.2%) and resulted in 1 additional visit (29.7%) and 1 phone call per patient (35.1%). The burdens of managing both diarrhea and nausea were similar, although diarrhea resulted in more phone calls to the healthcare provider. Conclusion: Diarrhea and nausea were common and resulted in an additional time and resource burden on dermatologists and their staff. Future research on the AE burden on providers and patients related to apremilast is needed.

Patient Profiles in Randomized Controlled Trials Versus a Real-World Study in Psoriatic Arthritis: Scoping Review and Metaanalysis.

Patients with psoriatic arthritis (PsA) in randomized controlled trials (RCTs) may not reflect patients with PsA in clinical practice. Our objective was to perform a metaanalysis comparing the characteristics of patients with PsA in RCTs of biologic disease-modifying antirheumatic drugs (bDMARDs) to patient profiles in a real-world study. Data sources included (1) a scoping literature review of phase III RCTs of bDMARDs in PsA published between 2015 and 2020, and (2) an international observational study of patients with PsA starting a bDMARD enrolled between 2015 and 2018 (PsABio; ClinicalTrials.gov: NCT02627768). Data collected at baseline included swollen and tender joint counts (SJC/TJC), presence of enthesitis, skin involvement (body surface area [BSA]), C-reactive protein (CRP), physician global assessment (PGA), and patient-reported outcomes (PROs; Health Assessment Questionnaire [HAQ], pain). Univariate random effects metaanalysis was conducted to calculate pooled means and proportions. Overall, 5654 patients from 10 RCTs were compared to 930 PsABio patients. Demographic data were similar. SJC/TJC were higher in RCTs than in PsABio (pooled means: 11.8/21.5 vs 5.7/11.9), and enthesitis was more frequent in RCTs (64.7% vs 48.2%), as were patients with a BSA ≥ 3% (62.2% vs 54%). PGA was higher in RCTs (59.7 vs 54.1). In contrast, PROs were similar, whereas CRP was significantly higher in PsABio (1.4 vs 1.1 mg/dL). Patients with PsA starting a bDMARD in RCTs had highly active disease and a high patient-reported disease burden. In contrast, PsABio real-world patients starting a bDMARD had lower SJC/TJC, skin involvement, and PGA, but presented with similar patient-reported disease burden. The extrapolation of RCT data in clinical practice should take these elements into account.

Real-world patient experience with medicinal cannabis use for symptom management in an Australian advanced cancer setting: a mixed method, cohort study using the theory of planned behaviour framework

PurposePatient hesitancy to use MC due to the fear of negative social implications leads to intentional non-adherence and compromises therapeutic outcomes. Hence, we aimed to determine the rate of patient adherence to MC and explore factors influencing patient MC use.MethodsDemographic and quantitative data related to MC usage were extracted from medical records for patients prescribed MC at a single cancer centre in metropolitan Sydney. Qualitative data was generated from semi-structured interviews. Interview guides were developed based on the Theory of Planned Behaviour (TBP) domains (i.e. Attitudes, Subjective Norms, Behavioural Intention and Perceived Behavioural Control) to elucidate themes influencing MC use. A mixed method approach involving triangulation of quantitative and qualitative methods was used for data analysis.ResultsTwenty patients were included in the study, and the majority of patients showed adherence (n = 14, 70%). The MC formulation used (p = .018), symptom relief (p = .001) and side effects experienced (p = .007) significantly influenced MC adherence. In addition to side effects experienced, findings for barriers to adherence were convergent or complementary for other medication-related factors, including the inconvenience of MC co-administration with food, cost and unpleasant taste.ConclusionsMC adherence is influenced by its effectiveness for symptom relief whereby appropriate MC formulation selection is crucial and should be determined by the indication (or symptom clusters). Social factors such as the views and experiences of close others had little bearing on MC adherence.

Real-World Outcomes of Selective RET Inhibitor Selpercatinib in the United States: Descriptive, Retrospective Findings from Two Databases.

This study described real-world patient characteristics and outcomes among selpercatinib-treated patients in the United States, using the Flatiron Health electronic health record-derived deidentified database (FHD) for advanced/metastatic non-small cell lung cancer (a/mNSCLC) and Optum's de-identified Clinformatics® Data Mart Database (CDM). Patients initiating selpercatinib treatment between 08MAY2020 and 30JUN2023 were included. We evaluated real-world time to selpercatinib treatment discontinuation or death (rwTTDd) and time to next treatment or death (rwTTNTd) using Kaplan-Meier analyses. Medication possession ratio (MPR) was estimated as a measure of medication adherence in CDM patients. In a/mNSCLC patients from the FHD (N = 68), the median rwTTDd and rwTTNTd were 22.4 [95%CI: 13.3-NR] and 21.0 [95%CI: 11.6-NR] months, respectively. In CDM, these durations were 12.1 [95%CI: 9.6-NR] and 16.2 [95%CI: 9.6-NR] months for lung cancer (n = 43), while these were not reached for thyroid cancer (n = 24) patients. The median MPR was 0.98 [IQR: 0.84-1.00] among all patients in the CDM (N = 75), with 77.3% of patients adhering (MPR ≥ 0.80) to selpercatinib. Real-world outcomes in this older and frailer patient cohort align with phase 3 trial results, further supporting selpercatinib as the standard of care for patients with RET-altered cancers. Early testing for the detection of RET alterations remains essential.

Abstract 4120534: Long-Term Outcomes After Medication, Coronary Stenting or Surgery for Men and Women With Three-Vessel Coronary Disease

Background: Sex is a vital prognostic factor in patients with coronary heart disease, however, the data on sex-treatment interaction among real-world patients with three-vessel coronary disease (TVD) are limited. Objectives: This study aimed to investigate the long-term outcomes after medication therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass grafting surgery (CABG) according to sex in patients with TVD. Methods: Consecutive 8943 patients with TVD [2421 (27.1%) MT, 3825 (42.8%) PCI, and 2697 (30.2%) CABG] were enrolled from April 2004 to February 2011 at Fu Wai Hospital. The primary endpoint was cardiac death and major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction (MI), stroke or repeat revascularization. The secondary endpoints were the components of MACCE. Results: Among 8943 TVD patients, 7122 (79.6%) were men and 1821 (20.4%) were women. While the number of women undergoing PCI was comparable to men, women opted for more MT and fewer CABG (Figure 1). During a median 6.6-year follow-up, CABG showed a lower risk of MACCE compared to PCI, with a similar treatment effect for women and men (female HR: 0.76; 95% CI: 0.60 to 0.97; male HR: 0.61, 95% CI: 0.55 to 0.69; p for interaction=0.222) (Figure 2 and Figure 3). CABG also showed lower risks of all-cause death, MI, and repeat revascularization, and a higher risk of stroke, which had no significant interaction with sex. PCI, compared to MT, was associated with lower risks of MACCE, all-cause death, and stroke and a higher risk of MI and repeat revascularization, without significant gender disparities. CABG versus MT was associated with lower risks of MACCE, all-cause death, MI and repeat revascularization and a higher risk of stroke, with a similar treatment effect for female and male patients (Figure 3). Conclusion: There was no significant sex differences in the risks of long-term outcomes of PCI vs. CABG, PCI vs. MT, and CABG vs. MT in real-world TVD patients.