Real-world Evidence Research Articles

Clinical and Diagnostic Utility of Genomic Profiling for Digestive Cancers: Real-World Evidence from Japan

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.

Tocilizumab in Severe and Critical COVID-19 Pneumonia: Streamlining the Mixed Signals

Four years since the start of the pandemic, the first lockdown in Manila happened on March 15, 2020 causing a pandemonium in the metro as the Filipinos gear up for the unexpected. As the suspected and confirmed cases grew, case numbers of unidentified patients soon became friends, relatives, and loved ones. As of May 2023 1 , there have been more than 1.3 million confirmed COVID-19 cases in Metro Manila alone with almost 14,000 deaths from severe and critical cases.
 The current knowledge about the disease as well as the explanation of its widely varied symptomatology continues to evolve. 2-4 At the center of the discussion for severe and critical COVID-19 requiring hospitalization is the hyperactivation ofthe inflammatory response resulting to simultaneous increase in multiple cytokines. 4,5 Such an inflammatory cascade results in nonspecific inflammatory reaction from damaged or dysfunctional virus-infected host cells making it difficult to identify a specific mediator of inflammatory response. 5,6 It is therefore not surprising that multiple therapeutic trials done targeting specific cytokines such as IL-6 and TNF-a have also led to mixed results. 7-10
 Since 2020, aggressive research has allowed both the development of new medications as well as repurposing of other molecules in the treatment of COVID-19. Antiviral drugs, monoclonal antibodies, IL-6R inhibitor/immune modulators, andsystemic corticosteroids have become household names. 6 IL-6, an identified key propagator of the cytokine storm in severe and critical COVID, has been the focus of the noise as mechanistically, IL-6 blockers including tocilizumab and sarilumabtheoretically disrupt the inflammatory cascade. 5-7
 If mechanistically, IL-6 blockers, particularly tocilizumab can block the inflammatory cascade, why are there mixed signals on its benefit based on real-world evidence? 7-10
 One of the largest and most recently published systematic review and meta-analysis of 15 randomized and two non- randomized clinical trials evaluating the effect of tocilizumab on the clinical outcomes of COVID-19 patients11 showed acombined cumulative risk of death in COVID-19 patients of 0.93 (RR 0.93, 95% CI 0.86 – 1.00, i 2 72.39%). The need for invasive ventilation, ICU admission was at 1.04 (RR 1.04, 95% CI 0.90 – 1.20, i 2 0.00). These figures indicate a 7% decreasedrisk of death with a 4% increased risk of ICU admission and need for invasive ventilation, again indicating mixed signals on the perceived benefit of tocilizumab. 11 Limitations in the study results compared to controlled clinical trials are probablydue to (1) heterogeneity of the patients with severe and critically ill COVID-19 patients potentially having different degrees of inflammatory activities; (2) timing of administration of tocilizumab; (3) different administrative and hospital policies inthe management of more ill patients suffering from COVID-19; and (4) presence of multiple inflammatory cytokines aside from IL-6, making it difficult to pinpoint the specific key mediator of inflammatory response on a per-patient basis.
 The local randomized controlled trial published by Amante et al.12 agree with these mixed signals from the published literature in COVID-19. In both intention-to-treat and per-protocol-analysis, there was no statistical significance and clinicalbenefit of using tocilizumab for severe and critically ill patients. Four years later, the picture is clearer now as real-world evidence coupled with carefully conducted clinical trials provide us a better understanding of the use of tocilizumab for current cases. However, back in 2020, when this mysterious respiratory illness is wreaking havoc, medications both newly developed and repurposed were offered as the medical research community was challenged by a pandemic in an unprecedented manner.
 As COVID-19 becomes endemic, the search for the cure for severe COVID-19 remains to be discovered. Given its mixed signals, shared decision making (pending confirmation in further studies) between the patient, caregiver, and the physician remains the cornerstone of management.

Long-term follow up of alemtuzumab-treated patients: a retrospective study in a Belgian tertiary care center.

Pivotal studies have reported a significant proportion of patients achieving no evidence of disease activity (NEDA) after 2 cycles of treatment with alemtuzumab (ATZ), that can be maintained for several years. Long-term real-world evidence regarding ATZ as well as subsequent treatment trajectories is still scarce. To analyze the effectiveness and safety of ATZ-treated patients in a tertiary care Belgian center. A retrospective cohort study including 32 patients treated with ATZ between 2015 and 2021 was performed. 32 patients received 2 ATZ courses with a mean follow-up (FU) duration of 5.6years (range: 2.25-8.2). 21.75% patients were treatment naïve. 40.5% were previously treated with natalizumab or fingolimod. NEDA-3 was achieved in 61.3-85% of patients, with failure mostly attributed to recurrence of radiological disease activity. During FU, annualized relapse rates remained very low (0.06-0.14), disability improvement occurred in up to 40.5%, whereas disability worsening occurred in up to 13.5%. Retreatment risk was associated with younger age (< 45years old, Odds Ratio 8.0, p = 0.02) and a higher number of previous DMTs (Hazard ratio 2.7, 95%CI 1.3-7.4, p = 0.02). Safety in our cohort was consistent with the known profile of ATZ. At the end of FU, 65.6% patients remained untreated after 2 or 3 courses of ATZ, while the remaining switched to anti-CD20 therapy or cladribine. ATZ is a high efficacy therapy for active MS, providing long-term remission in a significant proportion of patients. Retreatment was more frequent in younger patients or patients having failed a higher number of previous DMTs.

Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. TheCOMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30days during the follow-up period. These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Early use of high-efficacy therapies in multiple sclerosis in the United States: benefits, barriers, and strategies for encouraging adoption.

Multiple sclerosis (MS) is characterized by progressive neuroinflammation and neurodegeneration from disease onset that, if left untreated, can result in the accumulation of irreversible neurological disability. Early intervention with high-efficacy therapies (HETs) is increasingly recognized as the best strategy to delay or mitigate disease progression from the earliest stages of the disease and to prevent long-term neurodegeneration. Although there is growing clinical and real-world evidence supporting early HET intervention, foregoing this strategy in favor of a traditional escalation approach prioritizing lower-efficacy disease-modifying therapies remains a common approach in clinical practice. This review explores potential health care professional- and patient-related barriers to the early use of HETs in patients with MS in the United States. Barriers can include regulatory and reimbursement restrictions; knowledge gaps and long-term safety concerns among health care professionals; and various individual, cultural, and societal factors affecting patients. Potential strategies for overcoming these barriers and encouraging early HET use are proposed.

ESMO Guidance for reporting oncology real-world evidence (GROW)

The European Society for Medical Oncology (ESMO) has produced the very first expert-based guidance for reporting real-world evidence (RWE) studies specifically for oncology. The publication addresses nuances of modern RWE research in oncology and provides a comprehensive list of detailed key recommendations — that have also been transcribed into an interactive informative scoring checklist tool — for full article development in different RWE research scenarios.

Real-world evidence of treatment patterns and survival of metastatic gastric cancer patients in Germany

BackgroundPatients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients.MethodsA retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan–Meier method.ResultsThe cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 – 13.3 months] vs. 3.7 months [95%CI 3.4 – 4.0 months]).ConclusionSystemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population.

Predictors of Survival, Treatment Modalities, and Clinical Outcomes of Diffuse Large B-Cell Lymphoma in Patients Older Than 70 Years Still an Unmet Medical Need in 2024 Based on Real-World Evidence

Background: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials. Methods: This retrospective, observational, and single-center real-world study included 185 DLBCL, NOS patients older than 70 years treated at the largest oncology center in Latin America from 2009 to 2020. We aimed to assess the outcomes, determine survival predictors, and compare responses and toxicities between three different primary therapeutic strategies, including the conventional R-CHOP regimen and the attenuated R-MiniCHOP and R-MiniCHOP of the elderly protocols. Results: The median age at diagnosis was 75 years (70–97 years), and 58.9% were female. Comorbidities were prevalent, including 19.5% with immobility, 28.1% with malnutrition, and 24.8% with polypharmacy. Advanced clinical stage was observed in 72.4%, 48.6% had bulky disease ≥7 cm, 63.2% had B-symptoms, and 67.0% presented intermediate–high/high-risk IPI. With a median follow-up of 6.3 years, the estimated 5-year OS and PFS were 50.2% and 44.6%, respectively. The R-MiniCHOP of the elderly regimen had a lower ORR (p = 0.040); however, patients in this group had higher rates of unfavorable clinical and laboratory findings, including hypoalbuminemia (p = 0.001), IPI ≥ 3 (p = 0.013), and NCCN-IPI ≥ 3 (p = 0.002). Although associated with higher rates of severe neutropenia (p = 0.003), the R-CHOP regimen promoted increased OS (p = 0.003) and PFS (p = 0.005) in comparison to the attenuated protocols. Additionally, age ≥ 75 years, high levels of LDH, B-symptoms, advanced clinical stage (III/IV), neutrophilia, and low lymphocyte/monocyte ratio were identified as poor prognostic factors in this cohort. Conclusions: In this large and real-life Latin American cohort, we demonstrated that patients with DLBCL, NOS older than 70 years still do not have satisfactory clinical outcomes in 2024, with half of cases not reaching 5 years of life expectancy after diagnosis. Although the conventional R-CHOP offers response and survival advantages over attenuated regimens, its myelotoxicity is not negligible. Therefore, the outcomes reported and the prognostic factors here identified may assist clinicians in the appropriate selection of therapeutic strategies adapted to the risk for old and very old DLBCL patients.

Comparing the outcomes and costs of cardiac monitoring with implantable loop recorders and mobile cardiac outpatient telemetry following stroke using real-world evidence.

Aim: Patients with ischemic stroke (IS) commonly undergo monitoring to identify atrial fibrillation with mobile cardiac outpatient telemetry (MCOT) or implantable loop recorders (ILRs). The authors compared readmission, healthcare cost and survival in patients monitored post-stroke with either MCOT or ILR. Materials & methods: The authors used claims data from Optum's de-identified Clinformatics® Data Mart Database to identify patients with IS hospitalized from January 2017 to December 2020 who were prescribed ambulatory cardiac monitoring via MCOT or ILR. They compared the costs associated with the initial inpatient visit as well as the rate and causes of readmission, survival and healthcare costs over the following 18months. Datasets were balanced using patient baseline and hospitalization characteristics. Multivariable generalized linear gamma regression was used for cost comparisons. Cox proportional hazard regression was used for survival and readmission analysis. Sub-cohorts were analyzed based on the severity of the index IS. Results: In 2244 patients, readmissions were significantly lower in the MCOT monitored group (30.2%) compared with the ILR group (35.4%) (hazard ratio [HR] 1.23; 95% CI: 1.04-1.46). Average cost over 18months starting with the index IS was $27,429 (USD) lower in the MCOT group (95% CI: $22,353-$32,633). Survival difference bordered on statistical significance and trended to lower mortality in MCOT (8.9%) versus ILR (11.3%) (HR 1.30; 95% CI: 1:00-1.69), led by significance in patients with complications or comorbidities with the index event (MCOT 7.5%, ILR 11.5%; HR 1.62; 95% CI: 1.11-2.36). Conclusion: The use of MCOT versus ILR as the primary monitor following IS was associated with significant decreases in readmission, lower costs for the initial IS and total care over the next 18months, significantly lower mortality for patients with complications and comorbidities at the index stroke, and a trend toward improved survival across all patients.

Real-world evidence on tagraxofusp for blastic plasmacytoid dendritic cell neoplasm – collected cases from a single center and case reports

IntroductionBlastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare, aggressive hematologic malignancy. Until recently, the only curative treatment consisted of intensive chemotherapy, followed by hematopoietic cell transplantation (HCT) in eligible adult cases. Tagraxofusp, a CD123-targeted protein-drug conjugate and the first approved targeted treatment for BPDCN, might enhance outcomes especially in patients not eligible for intensive therapies.MethodsHere, we report real-world outcomes of five male patients with a median age of 79 years who received tagraxofusp as first-line treatment for BPDCN.ResultsTagraxofusp was found to be well-tolerated in this elderly cohort, with only one patient requiring discontinuation. Three patients responded to the treatment (two patients achieved a CR and one patient achieved a partial response), of which two subsequently underwent allogeneic (allo) HCT. One patient is alive and well after ≥ 4 years after alloHCT, and one patient shows sustained CR after now 13 cycles of tagraxofusp. The other three patients died of progressive disease 4-11 months after initiation of treatment.DiscussionIn line with results from 13 published cases outside clinical trials in the literature, sustained responses were associated with CR after tagraxofusp treatment and subsequent alloHCT. Our results provide real-world evidence for safety and efficacy of tagraxofusp as first-line treatment for BPDCN.

Rheumatoide Arthritis: Langzeitverläufe haben sich seit Einführung von Biologika und gezielter Therapie verbessert

&lt;b&gt;Background:&lt;/b&gt; Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. &lt;b&gt;Methods:&lt;/b&gt; Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. &lt;b&gt;Results:&lt;/b&gt; We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. &lt;b&gt;Conclusions:&lt;/b&gt; With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.

Real-world evidence of efficacy of pembrolizumab plus chemotherapy and nivolumab plus ipilimumab plus chemotherapy as initial treatment for advanced non-small cell lung cancer.

For advanced non-small cell lung cancer (NSCLC), combination therapies including a PD-1 inhibitor plus chemotherapy or a PD-1 inhibitor, CTLA-4 inhibitor, and chemotherapy are standard first-line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real-world setting. In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first-line therapies in 182 patients with stage IIIB-IV NSCLC. Primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan-Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD-L1 expression. In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3-4 adverse events occurred comparably, but immune-related adverse events were numerically more frequent in the CNI group. In real-world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC.

Age-specific Risk of Parkinson’s Disease and Parkinsonian Syndrome in Patients with Type 1 Gaucher Disease: Real-world Evidence from the International Collaborative Gaucher Group Gaucher Registry (P2-3.001)

Age-specific Risk of Parkinson’s Disease and Parkinsonian Syndrome in Patients with Type 1 Gaucher Disease: Real-world Evidence from the International Collaborative Gaucher Group Gaucher Registry (P2-3.001)

Real-world Evidence on Treatment Retention, Safety, and Tolerability of Edaravone in Canadian Patients with Amyotrophic Lateral Sclerosis (P5-11.012)

Real-world Evidence on Treatment Retention, Safety, and Tolerability of Edaravone in Canadian Patients with Amyotrophic Lateral Sclerosis (P5-11.012)

Real-world Evidence of Efficacy, Use, and Discontinuation of Pharmacotherapies for the Treatment of Essential Tremor (P3-3.006)

Real-world Evidence of Efficacy, Use, and Discontinuation of Pharmacotherapies for the Treatment of Essential Tremor (P3-3.006)

Cardiovascular events among patients with prostate cancer treated with abiraterone and enzalutamide.

There is growing concern about the adverse metabolic and cardiovascular effects of abiraterone acetate (AA) and enzalutamide (ENZ), two standard hormonal therapies for prostate cancer. We analysed the risk of cardiovascular adverse events among patients treated with AA and ENZ. We used Kythera Medicare data from January 2019 to June 2023 to identify patients with at least one pharmacy claim for AA or ENZ. The index date was the first prescription claim date. Patients were required to have 1 year of data pre- and post-index date. New users excluded those with prior AA or ENZ claims and pre-existing cardiovascular comorbidities. Demographic and clinical variables, including age, socioeconomic status (SES), comorbidity score, prostate-specific comorbidities, and healthcare costs, were analysed . Propensity score matching was employed for risk adjustment. Of the 8,929 and 8,624 patients in the AA and ENZ cohorts, respectively, 7,647 were matched after adjusting for age, sociodemographic, and clinical factors. Between the matched cohorts (15.54% vs. 14.83%, p < 0.05), there were no statistically significant differences in any cardiovascular event after adjusting for these factors. The most common cardiovascular event in both cohorts was heart failure (5.20% vs. 4.49%), followed by atrial fibrillation (4.42% vs. 3.60%) and hypotension (2.93% vs. 2.48%). This study provides real-world evidence of the cardiovascular risk of AA and ENZ that may not appear in clinical trial settings. Adjusting for age, baseline comorbidities, and SES, the likelihood of a cardiovascular event did not differ between treatment groups.

Comparative Effectiveness of Placental Allografts in the Treatment of Diabetic Lower Extremity Ulcers and Venous Leg Ulcers in U.S. Medicare Beneficiaries: A Retrospective Observational Cohort Study Using Real-World Evidence.

Objective: To compare the effectiveness of cellular tissue products (CTP) versus standard care in U.S. Medicare beneficiaries with diabetic lower extremity ulcers (DLEUs) or venous leg ulcers (VLUs). Approach: We performed a retrospective cohort study using real-world evidence from U.S. Medicare claims for DLEUs or VLUs between 2016 and 2020. There were three cohorts evaluated: viable cryopreserved placental membrane (vCPM) or viable lyopreserved placental membrane (vLPM); other CTP; and standard care. Claims were collapsed into episodes of care. Univariate and bivariate statistics were used to examine the frequency distribution of demographics and clinical variables. Multivariable zero-inflated binomial regressions were used to evaluate mortality and recurrence trends. Logistic regression compared three adverse outcomes (AOs): amputation; 1-year mortality; and wound recurrence. Results: There were 333,362 DLEU episodes among 261,101 beneficiaries, and 122,012 VLU episodes among 80,415 beneficiaries. DLEU treatment with vLPM was associated with reduced 1-year mortality (-26%), reduced recurrence (-91%), and reduced AOs (-71%). VLU treatment with vCPM or vLPM was associated with reduced 1-year mortality (-23%), reduced recurrence (-80%), and 66.77% reduction in AOs. These allografts were also associated with a 49% and 73% reduced risk of recurrence in DLEU and VLU, respectively, compared with other CTPs. Finally, vCPM or vLPM were associated with noninferior prevention of AOs related to amputation, mortality, and recurrence (95% CI: 0.69-1.14). Conclusions: DLEUs and VLUs treated with vCPM and vLPM allografts are associated with lowered 1-year mortality, wound recurrence, and AOs in DLEUs and VLUs compared with standard care. Decision makers weighing coverage of placental allografts should consider these added short- and long-term clinical benefits relative to costly management and high mortality of Medicare's most frequent wounds.

Canakinumab treatment real world evidence in 3 monogenic periodic fever syndromes in 2009–2022: an interim analysis using the French JIR cohort database

BackgroundOur study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS).MethodsThis study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study.Results31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab.ConclusionThis interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

Renal Denervation for Uncontrolled Hypertension

What Is the Issue?&#x0D; &#x0D; It is estimated that 23% of adults in Canada have hypertension. About 1/3 of this population have uncontrolled hypertension, a condition in which (BP) blood pressure levels continue to remain high despite treatment. People with high BP despite being prescribed 3 or more blood pressure-lowering (antihypertensive) medicines are considered to have uncontrolled resistant hypertension.&#x0D; Renal denervation is a therapy that involves disrupting activity in the sympathetic nerves in the renal artery using a minimally invasive catheter-based procedure to treat high BP.&#x0D; We wanted to know if renal denervation would effectively and safely reduce BP in people with uncontrolled hypertension.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; We identified and summarized the literature comparing the clinical effectiveness and safety of renal denervation in individuals with uncontrolled hypertension to help guide decisions on the use of this intervention.&#x0D; An information specialist searched for peer-reviewed and grey literature sources published between January 1, 2019, and February 5, 2024. The search was limited to English-language documents. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; The evidence for this report was based on 2 systematic reviews and 3 randomized controlled trials (RCTs).&#x0D; Renal denervation could lead to a reduction in BP compared to sham in adults with uncontrolled nonresistant hypertension.&#x0D; It is uncertain if renal denervation is an effective treatment for resistant hypertension and suspected hypertensive heart disease due to the methodological limitations of the included studies.&#x0D; Serious side effects of renal denervation were rare.&#x0D; &#x0D; What Does This Mean?&#x0D; &#x0D; Our findings agree with evidence-based guidelines and real-world evidence that suggest renal denervation can be considered a treatment option for patients with uncontrolled nonresistant hypertension. Other factors, including costs and resources, equity, acceptability, and patient selection, should be considered when implementing renal denervation in Canada, where it remains an emerging medical technology.&#x0D; Future research should assess important patient outcomes, such as quality of life.&#x0D;