scholarly journals Real-World Evidence of Caplacizumab Use in the Management of Acute TTP

Blood ◽  
2020 ◽  
Author(s):  
Tina Dutt ◽  
Rebecca J Shaw ◽  
Matthew James Stubbs ◽  
Jun Yong ◽  
Benjamin Bailiff ◽  
...  
Keyword(s):  
Platelet Count ◽  
Real World ◽  
Patient Characteristics ◽  
Patient Access Scheme ◽  
Fda Approval ◽  
Immune Mediated ◽  
Real World Evidence ◽  
Life Saving ◽  
The Uk ◽  
Von Willebrand

The cornerstone of life-saving therapy in immune mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody, trialled in two multicentre, randomised-placebo-controlled trials leading to EU and FDA approval, has been available in the UK through a patient-access scheme. Data was collected retrospectively from 2018-2020 for 85 patients receiving caplacizumab, including 4 children, from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial endpoints and historical outcomes in the pre-caplacizumab era. 84/85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalisation (3 days), duration of PEX (7 days) and hospital stay (12 days) was comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalisation was favourable compared with historical outcomes (p<0.05). TTP recurrence occurred in 5/85 patients; all with persistent ADAMTS13 activity <5iu/dL. Of 31 adverse events in 26 patients, 17/31 (55%) were bleeding episodes and 5/31 (16%) were thrombotic events (two unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4/5 deaths caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients receiving caplacizumab outside clinical trials, including paediatric patients. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

scholarly journals Caplacizumab Is Effective in Treating Immune-Mediated Thrombotic Thrombocytopenic Purpura in Real-World Scenarios and May Lower Mortality: An Aggregative Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1019-1019
Author(s):  
Linus A. Völker ◽  
Gesa Balduin ◽  
Lucas Kühne ◽  
Jessica Kaufeld ◽  
Ulf Schönermarck ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Real World ◽  
Prospective Trial ◽  
Patient Centered ◽  
Thrombocytopenic Purpura ◽  
Aggregated Data ◽  
Immune Mediated ◽  
Life Saving ◽  
The Uk ◽  
Historical Controls

Abstract Introduction: The treatment of acquired thrombotic thrombocytopenic purpura has been a subject to change lately due to the introduction of caplacizumab as a novel, and potentially life-saving agent. Here, we compare patient-centered outcomes of a historic cohort of 119 aTTP-patients and an extended real-world caplacizumab-treated cohort of 113 aTTP-patients from Germany and Austria in the context of multiple recently published international cohorts of aTTP patients. Methods: From October 2018 until May 2021, data from German and Austrian patients presenting with an acute episode of aTTP as defined by an ADAMTS13 activity below 10 % treated with caplacizumab were gathered retrospectively. We aggregated data from two published randomized controlled trials (TITAN, HERCULES), one single-arm prospective trial and two retrospective cohorts with a historical control cohort. In total, we report 846 aTTP cases, 396 of those treated with caplacizumab and 450 without. For data analysis, placebo groups from randomized trials and historical controls from retrospective analyses were combined. Results: All cohorts combined reported 30 aTTP-related deaths, predominantly in the non-caplacizumab cohort. Mortality in the caplacizumab-cohort (8 cases total) was mainly driven by 5 reported deaths in the UK-cohort, which have been ascribed to a delayed use of caplacizumab by the authors. The number of daily PEX was significantly less in the caplacizumab-treated cohort (7.2 vs 10.2 days). In line, the number of hospital (14.0 vs 18.1) and ICU (4.7 vs 8.9) days differed significantly. Exacerbations (14% vs 39%) were significantly reduced in the caplacizumab-group. In view of all treatment-related outcomes, the data presented herein argues strongly in favor of an early and consistent use of caplacizumab in all instances of aTTP. Disclosures Völker: Sanofi-Genzyme: Honoraria, Other: counselling fees.

scholarly journals Multi-Drug Featurization and Deep Learning Improve Patient-Specific Predictions of Adverse Events

2021 ◽  
Vol 18 (5) ◽  
pp. 2600
Author(s):  
Ioannis N. Anastopoulos ◽  
Chloe K. Herczeg ◽  
Kasey N. Davis ◽  
Atray C. Dixit
Keyword(s):  
Machine Learning ◽  
Real World ◽  
Variable Number ◽  
Patient Specific ◽  
Real World Evidence ◽  
Genetic Features ◽  
The Uk ◽  
Therapeutic Compounds ◽  
Improve Patient ◽  
Reaction Profile

While the clinical approval process is able to filter out medications whose utility does not offset their adverse drug reaction profile in humans, it is not well suited to characterizing lower frequency issues and idiosyncratic multi-drug interactions that can happen in real world diverse patient populations. With a growing abundance of real-world evidence databases containing hundreds of thousands of patient records, it is now feasible to build machine learning models that incorporate individual patient information to provide personalized adverse event predictions. In this study, we build models that integrate patient specific demographic, clinical, and genetic features (when available) with drug structure to predict adverse drug reactions. We develop an extensible graph convolutional approach to be able to integrate molecular effects from the variable number of medications a typical patient may be taking. Our model outperforms standard machine learning methods at the tasks of predicting hospitalization and death in the UK Biobank dataset yielding an R2 of 0.37 and an AUC of 0.90, respectively. We believe our model has potential for evaluating new therapeutic compounds for individualized toxicities in real world diverse populations. It can also be used to prioritize medications when there are multiple options being considered for treatment.

PP205 The Use Of Real-World Evidence To Support National Institute For Health And Care Excellence Medical Technology Submissions

2021 ◽  
Vol 37 (S1) ◽  
pp. 26-26
Author(s):  
Scott Gibson ◽  
Sita Saunders ◽  
Maximilian Blüher ◽  
Amanda Hansson Hedblom ◽  
Rafael Torrejon Torres ◽  
...  
Keyword(s):  
Decision Making ◽  
Real World ◽  
Trial Design ◽  
Clinical Evidence ◽  
Patient Characteristics ◽  
The United Kingdom ◽  
Real World Evidence ◽  
Guidance Documents ◽  
Meta Analyses ◽  
Positive Recommendation

IntroductionAlthough randomized controlled trials (RCTs) are recognized as providing the highest level of clinical evidence, few medical device RCTs are available due to underfunding or inherent challenges associated with trial design. This study examines the extent to which real-world evidence (RWE) supports the recommendations made by the National Institute for Health and Care Excellence Medical Technologies Evaluation Programme (MTEP).MethodsAll MTEP guidance documents published online prior to October 2020 were reviewed. The “case for adoption” recommendation, type of clinical data, and clinical critiques for each MTEP submission were extracted and categorized. RWE was defined as studies with neither blinding nor prospective selection or control of patient characteristics.ResultsOf the MTEP submissions reviewed, 34 of 45 (76%) received a positive recommendation. Independent of outcome, all submissions included RWE, but only 19 (42%) utilized RCT evidence (15 were recommended and four were not). Meta-analyses of RWE were used whenever possible. The most common clinical critiques in unsuccessful submissions were the following: (i) not generalizable to the United Kingdom National Health Service (NHS); (ii) low quality; (iii) likelihood of bias; (iv) trial design faults; (v) uncertain benefit; and (vi) evidence unrelated to scope.ConclusionsThis study suggests that while the use of RCTs has not always led to a positive recommendation, RWE can be valuable in decision-making. Evidence that is generalizable to the NHS, is related to the scope, and shows clear indication of benefit is more likely to positively influence MTEP decision-making.

Real-World Evidence in the Real World: Beyond the FDA

2018 ◽  
Vol 44 (2-3) ◽  
pp. 161-179 ◽  
Author(s):  
Joan H. Krause ◽  
Richard S. Saver
Keyword(s):  
Health Care ◽  
Health Care System ◽  
Real World ◽  
Regulatory Oversight ◽  
The Real ◽  
Health Care Fraud ◽  
Fda Approval ◽  
Real World Evidence ◽  
Potential Benefits ◽  
Care System

The 21st Century Cures Act (“Cures Act”) relies on the concept of real-world evidence (“RWE”) to improve the Food and Drug Administration (“FDA”) approval process. This has amplified interest and furthered momentum in applying RWE more broadly, beyond FDA regulation. In this article, we discuss the understandable appeal of RWE's pragmatic application and its many potential benefits. But we also caution that claims about RWE's wide-ranging, ameliorative impact on the health care system are likely overstated.The real world of RWE is messy and uncertain. Successfully incorporating RWE into regular health care system decision-making, beyond the FDA, faces considerable obstacles and limitations. We review the reasons to be wary about RWE as a game-changer. These concerns including data reliability, insufficient incentives for stakeholders to generate and engage with high-quality RWE, and lack of comprehensive regulatory oversight. In addition, the push for RWE may impact the enforcement of the health care fraud and abuse laws, perhaps not in necessarily positive ways. Increased reliance on RWE may have significant implications for off-label fraud enforcement, further conflating the distinction between claims that are false for reimbursement rather than for scientific purposes.

scholarly journals PMD24 - ASSOCIATION BETWEEN IOL DESIGN AND INCIDENCE OF PCO AND ND:YAG CAPSULOTOMY: A RETROSPECTIVE REAL WORLD EVIDENCE STUDY IN THE UK

2018 ◽  
Vol 21 ◽  
pp. S246
Author(s):  
M. Dhariwal ◽  
D. O'Boyle ◽  
C. Bouchet ◽  
J. Khan ◽  
A. Venerus ◽  
...  
Keyword(s):  
Real World ◽  
Real World Evidence ◽  
The Uk

scholarly journals Patient Characteristics and Treatment Patterns in the First-Line and Second-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the United Kingdom, France, and Germany

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4234-4234 ◽  
Author(s):  
Aaron Galaznik ◽  
Nate Way
Keyword(s):  
Systemic Therapy ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Current Treatment ◽  
Treatment Patterns ◽  
Initial Diagnosis ◽  
The United Kingdom ◽  
Real World Evidence ◽  
The Uk ◽  
Combination Regimens

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are hematologic malignancies with poor prognosis for patients who do not respond well to therapy. As current treatment options may be suboptimal for many patients, it is important to better understand the current treatment landscape for DLBCL and FL. Here we provide recent real-world evidence on patient characteristics and treatment patterns in relapsed/refractory (R/R) DLBCL and R/R FL across the United Kingdom (UK), France (FRA), and Germany (DE). Methods: Hematologists and oncologists (N=140) from the UK, FRA, or DE retrospectively identified patients diagnosed with R/R DLBCL or R/R FL who received at least two lines of therapy and had radiographically or clinically measurable disease with at least one target lesion per International Working Group criteria for malignant lymphoma. Descriptive statistics examined patient characteristics and treatment patterns in first-line (1L) and second-line (2L) therapy. Results: Mean (SD) age at initial diagnosis was 59.9 (10.9) years for the aggregate DLBCL patient sample (N=272). DLBCL patients were primarily male (69.1%), distributed across the UK (29.0%), FRA (36.8%), and DE (34.2%), and had various Eastern Cooperative Oncology Group (ECOG) performance statuses at initial diagnosis (0 ECOG 28.7%, 1 ECOG 48.9%, 2 ECOG 14.3%, ≥3 ECOG 5.9%, unknown ECOG 2.2%). Mean (SD) age at initial diagnosis was 61.0 (10.2) years for the aggregate FL patient sample (N=282). FL patients were primarily male (53.9%), distributed across the UK (29.4%), FRA (36.9%), and DE (33.7%), and had various ECOG performance statuses at initial diagnosis (0 ECOG 30.5%, 1 ECOG 50.7%, 2 ECOG 13.5%, ≥3 ECOG 4.2%, unknown ECOG 1.1%). DLCBL and FL patient characteristics by country are presented in Table 1. DLCBL patients in 1L and 2L received combination regimens (93.8% and 82.7%, respectively) or monotherapy regimens (6.2% and 17.3%, respectively). DLCBL patients in 1L received treatment largely consistent with current guidelines, consisting mainly of systemic therapy only (86.8%) and treatment with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP, 68.0%). DLCBL patients in 2L completed multiple therapy cycles (median 3 cycles) and were treated with systemic therapy only (79.4%), systemic therapy and radiation (4.0%), systemic therapy and stem cell transplantation (SCT, 16.2%), or systemic therapy, radiation, and SCT (0.4%). The most common 2L DLCBL regimens were: rituximab, dexamethasone, high-dose cytosine arabinoside, and cisplatin (R-DHAP, 19.5%); bendamustine plus rituximab (12.9%); rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX, 12.5%). FL patients in 1L and 2L received combination regimens (86.5% and 78.4%, respectively) or monotherapy regimens (13.5% and 21.6%, respectively). FL patients in 1L received treatment largely consistent with current guidelines, consisting mainly of systemic therapy only (90.8%) and treatment with R-CHOP (35.1%). FL patients in 2L completed multiple therapy cycles (median 4 cycles) and were treated with systemic therapy only (90.1%), systemic therapy and radiation (2.1%), systemic therapy and SCT (6.0%), or systemic therapy, radiation, and SCT (1.8%). The most common 2L FL regimens were: bendamustine plus rituximab (33.3%); R-CHOP (9.6%); R-DHAP (8.5%). DLCBL and FL 2L treatment patterns by country are presented in Table 2. Conclusion/Summary: Given the rapid evolution of therapies used to treat FL and DLBCL, these findings fill a crucial data gap in real-world evidence on patient characteristics and treatment patterns in R/R DLCBL and R/R FL in the UK, FRA, and DE. There is an unmet need in DLBCL and FL. As novel treatments for patients with DLBCL and FL are currently in development, it is important to better understand the patients being treated for these conditions and the current treatment landscape. Disclosures Galaznik: Takeda Pharmaceuticals International Co.: Employment. Way:Seattle Genetics: Research Funding; Kantar Health: Employment.

scholarly journals 1136P Feasibility of linking the UK 100,000 genomes project and real-world evidence databases for a melanoma patient population

2020 ◽  
Vol 31 ◽  
pp. S760-S761
Author(s):  
E. Scherrer ◽  
G.M. Hair ◽  
S. Mt-Isa ◽  
M. Pereira ◽  
G. Chan ◽  
...  
Keyword(s):  
Real World ◽  
Patient Population ◽  
Melanoma Patient ◽  
Real World Evidence ◽  
The Uk

Characteristics of patients receiving immune checkpoint inhibitors (ICI) in ASCO’s CancerLinQ.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2566-2566
Author(s):  
Wendy S. Rubinstein ◽  
Li Chen ◽  
George Anthony Komatsoulis ◽  
Edward Stepanski ◽  
Monika Jun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Real World ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Treatment Patterns ◽  
Disease Stage ◽  
Cancer Type ◽  
Lung Cancer Patients ◽  
Fda Approval

2566 Background: ICI’s have demonstrated significant clinical benefit since the first FDA approval in 2011 of ipilimumab for metastatic melanoma. Five additional ICI therapies have since been approved across several indications. The objectives of this study were to describe the clinical and demographic features of patients receiving ICI treatment along with utilization patterns in real-world settings. Methods: We conducted a retrospective, observational cohort study using statistically de-identified data from January 2011 to November 2018 in CancerLinQ, ASCO’s real-world oncology database, which now contains EHR data from 49 diverse oncology practices in the U.S. Adult patients diagnosed with any cancer type who received ≥1 dose of an ICI (see Table) and had ≥2 clinical visits were eligible for inclusion. Patients were excluded if they received an ICI prior to its first FDA approval date to avoid inclusion of clinical trial patients. Descriptive statistics were used to examine treatment patterns and clinical characteristics of patients receiving ICIs. Results: This analysis included 12,712 patients who received an ICI. Median patient age was 67.4 years [IQR 59.3, 75.3]; 58% were male. White race made up the highest percent (83%) of ICI patients, followed by Black race (9%) and Other (8%). The most common primary cancers at the start of treatment were lung cancer (36%), melanoma (8%), urothelial cancer (2%) and renal cell carcinoma (2%). Of the 8,444 patients with known disease stage, 5,446 (64%) had Stage IV cancer. Breakdown of ICI treatment patterns can be found in the accompanying table. Uptake of ICIs was the most rapid for nivolumab, which had the highest use (49%), followed by pembrolizumab for rapid adoption and use (30%). Conclusions: This analysis gives insights into patient characteristics and real-world treatment patterns for ICIs. ICIs were used most widely in males, lung cancer patients and patients with advanced disease. These baseline characteristics inform our analyses of ICI use in patients with autoimmune disease, also reported herein.[Table: see text]

First Real-world Evidence of Meningococcal Group B Vaccine, 4CMenB, Protection Against Meningococcal Group W Disease: Prospective Enhanced National Surveillance, England

2020 ◽  
Author(s):  
Shamez N Ladhani ◽  
Helen Campbell ◽  
Nick Andrews ◽  
Sydel R Parikh ◽  
Joanne White ◽  
...  
Keyword(s):  
Real World ◽  
Disease Surveillance ◽  
Age Cohorts ◽  
Poisson Models ◽  
Real World Evidence ◽  
Meningococcal Group ◽  
Adjusted Incidence Rate ◽  
Group B ◽  
The Uk ◽  
Adjusted Incidence

Abstract Background 4CMenB is a protein-based meningococcal B vaccine, but the vaccine antigens may be present on non–group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunization program, alongside an emergency adolescent meningococcal ACWY (MenACWY) program to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST-11 clonal complex. The adolescent program aimed to provide direct protection for adolescents and indirect protection across the population. Methods Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during 4 years before and 4 years after implementation of both vaccines were analyzed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB program along with the indirect impact of the adolescent MenACWY program in children eligible for 4CMenB but not MenACWY. Results Model estimates showed 69% (adjusted incidence rate ratio [aIRR], .31; 95% CI, .20–.67) and 52% (aIRR, .48; 95% CI, .28–.81) fewer MenW cases than predicted among age-cohorts that were fully- and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in <5-year-olds. 4CMenB directly prevented 98 (95% CI, 34–201) cases, while the MenACWY program indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over 4 years. Disease severity was similar in 4CMenB-immunized and unimmunized children. Conclusions This is the first real-world evidence of direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups.

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