scholarly journals P257 Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials?

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Gareth T Jones ◽  
Linda E Dean ◽  
Ejaz Pathan ◽  
Gary J Macfarlane
Keyword(s):  
Clinical Trials ◽  
Treatment Response ◽  
Real World ◽  
Financial Support ◽  
World Population ◽  
Research Support ◽  
Trial Participants ◽  
Tnf Inhibition ◽  
Grant Holder

Abstract Background The development and utility of management guidelines assumes that clinical trial findings are generalisable. Seldom is data available to test this. We aimed to determine, in the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS), the proportion of patients commencing TNF inhibition (TNFi) that would/would not have been eligible for clinical trials that led to TNFi treatment guidelines, and whether treatment response differed between the trials and this real-world population. Methods Biologic-naïve spondyloarthritis patients were recruited from across Great Britain. Data was obtained from clinical records, and participants completed postal questionnaires. Participant characteristics were extracted from the placebo-controlled randomised trials in the NICE Health Technology Assessment: TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis (TA383). Descriptive statistics were used to examine differences, including treatment response (ASAS-20), between BSRBR-AS participants who would/would not have been eligible for the clinical trials, and the trial participants. Results 816/2420 (34%) BSRBR-AS participants were commencing TNFi. They were younger (mean age 44 versus 50yrs) with shorter disease duration (15 versus 22yrs), more active disease (BASDAI 6.4 versus 4.0), and poorer function (BASFI 6.2 versus 3.8). Fourteen clinical trials were identified. Compared to trial populations, fewer BSRBR-AS participants were male (67% versus 71%; difference: -4.1% (95%CI: -7.8%, -0.4%)) and fewer were HLA-B27 positive (76% versus 82%; difference: -6.6% (-10.6%, -2.6%)). BSRBR-AS participants were 6yrs older than trial participants, with longer symptom duration. They reported similar disease activity (BASDAI: 6.4 versus 6.2; difference 0.2 (-0.3, 0.7)), although significantly poorer function (BASFI: 6.2 versus 5.1; difference 1.1 (0.5, 1.8)) and spinal mobility (BASMI: 4.2 versus 3.3; difference 1.0 (0.8, 1.1)). Only 333 (41%) of BSRBR-AS participants commencing TNFi would have been eligible for any of the relevant trials. Ten trials reported ASAS20 response criteria, and 864/1401 participants reported a positive treatment response (61.7%). Follow-up data was available for 318 (39%) BSRBR-AS participants, of whom 163 (51.3%) achieved an ASAS20 treatment response (difference: 10.4% (4.4%, 16.5%)). There was no difference in ASAS20 response between those who would/would not have been eligible for clinical trials (50% versus 52%; difference 2.0% (-9.4%, 13.4%)). Conclusion In this real-world population, although the likelihood of meeting response criteria was unrelated to factors determining trial eligibility, the proportion of patients responding to TNFi was lower than in the clinical trial literature. Could this be explained by selection bias? Although fewer BSRBR-AS participants provided follow-up data than in the clinical trials, to account for the observed difference participants lost to follow-up would have to be one-third more likely to achieve ASAS20 response than those who provided follow-up data. We believe this is unlikely. These findings have important implications for the generalisability of trial results, and also for the cost-effectiveness of TNFi agents. Disclosures G.T. Jones: Grants/research support; GTJ is/was a grant holder for research funded by Pfizer, AbbVie, UCB and Celgene., GTJ is/was involved in research that received financial support from Novartis. L.E. Dean: Grants/research support; LED is/was involved in research that received financial support from Pfizer, AbbVie, UCB and Novartis. E. Pathan: None. G.J. Macfarlane: Grants/research support; GJM is/was a grant holder for research funded by Pfizer, AbbVie, UCB and Celgene., GJM is/was involved in research that received financial support from Novartis.

scholarly journals Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials?

2020 ◽  
Vol 79 (7) ◽  
pp. 914-919 ◽  
Author(s):  
Gareth T Jones ◽  
Linda E Dean ◽  
Ejaz Pathan ◽  
Rosemary J Hollick ◽  
Gary J Macfarlane
Keyword(s):  
Clinical Trials ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Treatment Response ◽  
Real World ◽  
Axial Spondyloarthritis ◽  
British Society ◽  
Symptom Duration ◽  
Clinical Records ◽  
Trial Participants

Management guidelines assume that results from clinical trials can be generalised, although seldom is data available to test this assumption. We aimed to determine the proportion of patients commencing tumour necrosis factor inhibition (TNFi) who would have been eligible for relevant clinical trials, and whether treatment response differs between these groups and the trials themselves. The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited a real-world cohort of TNFi-naïve spondyloarthritis patients with data collection from clinical records and patient questionnaires. Participant characteristics were extracted from trials identified from a recent Health Technology Assessment of TNFi for ankylosing spondylitis/non-radiographic axial spondyloarthritis. Descriptive statistics were used to determine the differences, including treatment response, between BSRBR-AS participants who would/would not have been eligible for the clinical trials and with trial participants. Among 2420 BSRBR-AS participants, those commencing TNFi (34%) had shorter symptom duration (15 vs 22 years) but more active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 6.4 vs 4.0; Bath Ankylosing Spondylitis Disease Functional Index (BASFI) 6.2 vs 3.8). Of those commencing TNFi, 41% met eligibility criteria for ≥1 of fourteen relevant trials; they reported higher disease activity (BASDAI 6.9 vs 6.1) and poorer function (BASFI 6.6 vs 6.0). 61.7% of trial participants reported a positive treatment response, vs 51.3% of BSRBR-AS patients (difference: 10.4%; 95% CI 4.4% to 16.5%). Potential eligibility for trials did not influence treatment response (difference 2.0%; -9.4% to 13.4%). Fewer patients in the real world respond to TNFi than is reported in the trial literature. This has important implications for the generalisability of trial results, and the cost-effectiveness of TNFi agents.

Real-world experience of talimogene laherparepvec in patients receiving immunotherapy in metastatic melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22003-e22003
Author(s):  
Tapas Ranjan Behera ◽  
Jung Min Song ◽  
Jennifer S. Ko ◽  
Michael J. McNamara ◽  
Pauline Funchain ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Metastatic Melanoma ◽  
Treatment Response ◽  
Median Time ◽  
Real World ◽  
Overall Response Rate ◽  
Response Rate ◽  
Talimogene Laherparepvec ◽  
Overall Response

e22003 Background: Talimogene laherparepvec (TVEC) is an oncolytic herpes virus approved by the FDA for intralesional therapy in unresectable metastatic melanoma. However, little is known regarding the effectiveness of TVEC+checkpoint inhibition (CPI) outside of clinical trials. We present outcomes of the largest single institution experience with TVEC in the context of different immune checkpoint inhibitors. Methods: All patients with stage III-IV unresectable melanoma having received TVEC were evaluated. Patient demographics, clinicopathological characteristics, TVEC treatment response and outcomes were assessed. Final analysis included those who received TVEC adjacent to CPI with a minimum 6-month follow-up, excluding patients on clinical trials. Response was estimated by sequential measurement of injectable on-target lesions. Results: A total of 62 patients received TVEC from 2016 to 2019, of which 43 remained excluding Merkel cell carcinoma, patients on trials, and TVEC monotherapy. Of 30 patients with available treatment response data and at least 6-months follow-up, median age was 68.5 years (30-99 years), 40% were female, 16 (53.3%) stage IV. Median follow-up was 17.5 months (6-43 months). At 6 months, 20 (67.7%) patients were alive; at 1 year, 17 (56.7%) patients were alive. Eighteen patients received pembrolizumab, 7 nivolumab and 5 ipilimumab/nivolumab. Median number of TVEC doses received was 8 (3-31 doses). Median time on TVEC therapy was 4 months (1-26 months). Overall response rate for on-target lesions was 24 (80%), with complete local response (CR) in 15 (50%), partial response (PR) in 9 (30%), and progressive disease (PD) in 6 (20%). Median time to response was 6 weeks (2-17 weeks); 5 in CR, 6.5 in PR and 5.5 in PD groups. Adverse events were mostly mild and limited to constitutional symptoms. Conclusions: To our knowledge this is the largest real-world experience assessing TVEC in patients receiving CPI. Local overall response rate appears higher in comparison to historic numbers for TVEC monotherapy. The findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma and has robust outcomes in real-life clinical settings.

scholarly journals Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Recurrence Rates ◽  
Factors Associated ◽  
Clostridioides Difficile ◽  
Multicentre Cohort Study ◽  
Clostridioides Difficile Infection ◽  
Prevention Of Recurrence ◽  
Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

scholarly journals POS0866 TWO-DIMENSIONAL HRCT-BASED RADIOMIC FEATURES IN SSC-ILD DISTINGUISH DRUG RESPONDERS FROM NON-RESPONDERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 688-689
Author(s):  
C. Meier ◽  
M. Maciukiewicz ◽  
M. Brunner ◽  
J. Schniering ◽  
H. Gabrys ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Linear Regression ◽  
Lung Disease ◽  
Treatment Response ◽  
Two Dimensional ◽  
Research Support ◽  
Pre Treatment

Background:Management of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is complicated by high inter-patient variability. To date, no validated predictors of treatment response are available for routine use. High resolution computed tomography (HRCT)-based radiomics, i.e. the high-dimensional, quantitative analysis of imaging metadata, have previously been shown to be successful in discriminating (SSc-)ILD phenotypes in preclinical and clinical studies1. Since HRCT is an integral part of the routine work-up in SSc, HRCT-based radiomic features may hold potential as non-invasive biomarkers.Objectives:To predict treatment response using two-dimensional (2D) HRCT-based radiomics in SSc-ILD patients from a prospectively followed cohort.Methods:Inclusion criteria were diagnosis of SSc-ILD in HRCT, availability of a suitable chest HRCT scan within 12 months prior to initiation of a new treatment, and availability of clinical baseline and follow-up information. Treatment response was defined as the absence of all of the following over a follow-up period of 12-24 months: relative decrease in forced vital capacity (FVC) ≥5%, increase of ILD in HRCT as assessed by a radiologist, change in treatment regimen due to insufficient response, ILD-related death or lung transplantation. Of each pre-treatment HRCT, 6 slices (15±5 mm apart, starting from the basal lung margin) were manually segmented and 1513 2D radiomic features were extracted using the in-house software Z-Rad (Python 2.7). Features were Z-score transformed and pre-filtered for inter- and intra-reader robustness (intraclass correlation coefficient >0.85) and inter-feature correlation (Spearman’s rho <0.9). A categorical linear regression model was created using 3-fold cross-validated elastic nets for feature selection. Features were then summarized and divided by their number. For generation of a score cut-off, Youden’s score was used. For two-group analyses of continuous variables, Wilcoxon’s test was performed, whereas categorical data was assessed using Fisher’s exact test.Results:A total of 64 pre-treatment HRCTs from 54 patients were analyzed. In 9 patients, >1 asynchronous treatments were assessed, while 45 patients had only 1 eligible treatment approach. The response rate within the assessed follow-up period was 45.3% (n=29). For score generation, 13 radiomic features were selected and an optimal cut-off value of -0.1589 was determined. Univariate linear regression showed significant association between our categorical radiomics-based score and treatment response (p=0.007, area under the curve = 0.65 (0.51-0.79), sensitivity=0.90, specificity=0.43), whereby a high score was predictive for treatment response.No differences between patients with high (n=46) or low (n=18) scores were detected for baseline age (mean±SD=55.5±12.0 and 55.5±13.6 years, p=0.84), duration of SSc (mean±SD=6.2±8.4 and 4.7±4.4 years, p=0.79), time since ILD diagnosis (2.7±2.9 and 2.4±3.1 years, p=0.59), FVC (77.6±20.6 and 80.1±17.9, p=0.41) or DLco (54.4±21.0 and 57.6±18.9, p=0.40). Distribution of anti-Scl-70 positivity (45.7% vs. 55.6%, p=0.58) and diffuse cutaneous disease (47.7% vs. 61.1%, p=0.41) was not significantly different between patients with high and low scores, respectively, although a trend towards higher percentages in the high score group was observed.Conclusion:Our results indicate that, following validation in external cohorts, radiomics may be a promising tool for future pre-treatment patient stratification. Moreover, our radiomics-based score seems not to be associated with commonly studied clinical predictors such as anti-Scl-70 positivity or lung function, underlining a possible additive value to ‘traditional’ clinical parameters.References:[1]Schniering, J., et al. Resolving phenotypic and prognostic differences in interstitial lung disease related to systemic sclerosis by computed tomography-based radiomics. medRxiv [Preprint] doi:10.1101/2020.06.09.20124800 (2020).Disclosure of Interests:Chantal Meier: None declared, Malgorzata Maciukiewicz: None declared, Matthias Brunner: None declared, Janine Schniering: None declared, Hubert Gabrys: None declared, Anja Kühnis: None declared, Oliver Distler Speakers bureau: Speaker fee on Scleroderma and related complications: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche. Speaker fee on rheumatology topic other than Scleroderma: MSD, iQone, Novartis, Pfizer, Roche, Consultant of: Consultancy fee for Scleroderma and its complications: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Boehringer, CSL Behring, ChemomAb, Corbus Pharmaceuticals, Horizon Pharmaceuticals, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Roivant Sciences, Sanofi, UCB. Consultancy fee for rheumatology topic other than Scleroderma: Abbvie, Amgen, Lilly, Pfizer, Grant/research support from: Research Grants to investigate the pathophysiology and potential treatment of Scleroderma and its complications: Kymera Therapeutics, Mitsubishi Tanabe, Thomas Frauenfelder: None declared, Stephanie Tanadini-Lang: None declared, Britta Maurer Speakers bureau: Speaker fees from Boehringer-Ingelheim, Grant/research support from: Grant/research support from AbbVie, Protagen, Novartis Biomedical Research, congress support from Pfizer, Roche, Actelion, mepha, and MSD

FRI0362 COMPARATIVE EFFECTIVENESS OF USTEKINUMAB (UST) AND TNF INHIBITORS (TNFI) IN PATIENTS WITH PSORIATIC ARTHRITIS (PSA) IN THE REAL-WORLD, MULTINATIONAL PSABIO STUDY: 12-MONTH FOLLOW-UP

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 778-779
Author(s):  
J. S. Smolen ◽  
S. Siebert ◽  
T. Korotaeva ◽  
P. Bergmans ◽  
K. De Vlam ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Activity Index ◽  
Treatment Options ◽  
Disease Activity Index ◽  
Rapid Screening ◽  
Research Support ◽  
Real World Data

Background:Among treatment options for PsA, IL-12/23 inhibition with UST was the first new biologic mode of action after TNFi. Few real-world data comparing UST with TNFi are available.Objectives:Comparison of UST and TNFi treatment effectiveness within the prospectively followed PsABio cohort at 12-month (mo) follow-up.Methods:The PsABio study (NCT02627768) evaluates effectiveness, tolerability and persistence of 1st, 2nd or 3rd-line UST or TNFi in PsA. Proportions of patients (pts) reaching MDA/very low disease activity (VLDA) and clinical Disease Activity index for PSoriatic Arthritis (cDAPSA) LDA/remission are described. Comparison across UST and TNFi cohorts was done on last observation carried forward up to 12 (±3) mo, with non-response imputation for pts who had stopped/switched initial treatment. Logistic regression analysis was used, including propensity score (PS) analysis to adjust for imbalanced prognostic baseline (BL) covariates: country, age, sex, BMI, smoking (yes/no), comorbidities (cardiovascular/metabolic syndrome), PsA type (axial, polyarticular, oligoarticular), psoriasis body surface area (BSA), disease duration, cDAPSA, 12-item PsA Impact of Disease (PsAID-12), dactylitis, enthesitis, Fibromyalgia Rapid Screening Tool (FiRST) score, line of biologic (b)DMARD, synthetic DMARD use, and steroid or NSAID use.Results:Of 929 eligible pts, 893 had evaluable data at BL and at follow-up; 438 (95.6%) were treated with UST and 455 (96.6%) with TNFi (including stoppers/switchers). UST and TNFi groups had BL differences in mean age (51.0 vs 48.5 years, respectively), concurrent comorbidities (68.7% vs 60.9%), time since diagnosis (7.5 vs 6.2 years), line of treatment (1st-line 45.0% vs 55.2%; 3rd-line 20.5% vs 12.1%), NSAID use (54.8% vs 68.8%), concomitant MTX use (29.9% vs 42.0%) and psoriasis skin involvement (BSA >10% in 26.6% vs 14.8%).In 714 pts with available data, mean (standard deviation) BL cDAPSA was 30.6 (20.2; n=358) for UST and 29.3 (18.6; n=356) for TNFi. Observed data showed differences in proportion of pts achieving MDA/VLDA and cDAPSA LDA/remission in favour of TNFi, but after PS adjustment for BL differences (such as line of therapy, skin psoriasis, concomitant conventional DMARD, etc.), odds ratios for reaching targets at 12 mo did not significantly differ between UST and TNFi groups (Fig. 1).Comparison of 6- and 12-mo unadjusted data showed sustained MDA/VLDA responses with both UST (21.8%) and TNFi (29.5%), with comparable proportions of additional pts achieving these targets between 6 and 12 mo (17.0% and 20.3%, respectively). Sustained efficacy became lower with successive lines of treatment (data not shown).Conclusion:Various factors, including patient characteristics such as comorbidities, influence the physician’s selection of treatment modality for patients needing a bDMARD. Our real-world results demonstrate differences in observed clinical effectiveness between UST and TNFi. However, after PS adjustment for a number of BL differences, clinical results at 12 mo were comparable between UST and TNFi groups. Data at 12 mo also show sustained response with both UST and TNFi treatment, as well as a similar rate of pts achieving targets after 6 to 12 mo of treatment.Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Wim Noel Employee of: Janssen Pharmaceuticals NV, Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB

Abstract 15829: Temporal Characteristics of Intra-thoracic Impedance Before and After Heart Failure Hospitalizations in a Large Real-world Population of Patients With Cardiovascular Implanted Electronic Devices

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shantanu Sarkar ◽  
Jodi L Koehler ◽  
Eddy Warman
Keyword(s):  
Real World ◽  
Electronic Devices ◽  
Primary Diagnosis ◽  
Implantable Devices ◽  
World Population ◽  
Inclusion Criteria ◽  
Temporal Characteristics ◽  
Before And After ◽  
Intrathoracic Impedance

Introduction: Intrathoracic impedance (IMP), measured in ICD/CRTD implantable devices, is a measure of intravascular blood volume and have been shown to correlate with intracardiac pressures. We investigated the temporal characteristics of IMP before and after HF events (HFE) in a large real-world cohort of patients (pts) with ICD/CRTD devices. Methods: We linked Optum© deidentified EHR dataset during the period from 2007-2017 to the Medtronic CareLink data warehouse. Pts with ICD/CRTD implants with IMP measurements were included. HFE was defined as an inpatient, ED, or observation unit stay with primary diagnosis of HF and IV diuretics administration. Temporal average of IMP measurement across all pts in the 60 days pre and post HFE were compared for HFE with and without readmission for HF within 60 days and in pts with no HFE. Results: A total of 17,886 pts with 1.8±1.2 years of follow-up met inclusion criteria. The average age was 66.6 ±12.3 years, with 72% being males, and 51% with ICD devices. A total of 1174 pts had 1425 HFE with no readmission and 282 pts had 295 HFE which were followed by readmission. A total of 17,839 pts had no HFE over 86,858 follow-up months. The average IMP during HFE, with and without readmission, and in pts with no HFE are shown in Fig. IMP decreases over a period of time prior to HFE and recovers due to treatment during HFE. The average IMP across all patients was lower on all 60 days pre and post HFE with readmission compared to HFE with no readmission (p<0.001) and both were lower compared to follow-up period with no HFE (p<0.001). The IMP recovers less often after HF events which are followed by readmission within 60 days compared to HF events with no readmission. Conclusions: In a large real-world population of pts with ICD/CRTD devices, on an average IMP reduces prior to and recovers during HFE. IMP was lower before and after HFE with readmission compared to HFE with no readmission. Readmission is more likely in pts with smaller impedance recovery after HF events.

scholarly journals Challenges in Tuberculosis Clinical Trials in the Face of the COVID-19 Pandemic: A Sponsor’s Perspective

2020 ◽  
Vol 5 (2) ◽  
pp. 86
Author(s):  
I.D. Rusen
Keyword(s):  
Clinical Trials ◽  
Safety Monitoring ◽  
Chain Management ◽  
Mdr Tb ◽  
The Face ◽  
System Functioning ◽  
Treatment Continuity ◽  
The Impact ◽  
Trial Participants

The COVID-19 pandemic has caused unforeseen and extreme changes in societal and health system functioning not previously experienced in most countries in a lifetime. The impact of the pandemic on clinical trials can be especially profound given their complexities and operational requirements. The STREAM Clinical Trial is the largest trial for MDR-TB ever conducted. Currently operating in seven countries, the trial had 126 participants on treatment and 312 additional participants in active follow up as of March 31, 2020. Areas of particular concern during this global emergency include treatment continuity, supply chain management and participant safety monitoring. This commentary highlights some of the challenges faced due to the pandemic and the steps taken to protect the safety of trial participants and the integrity of the trial.

scholarly journals A Distribution-based Method for Assessing The Differences between Clinical Trial Target Populations and Patient Populations in Electronic Health Records

2014 ◽  
Vol 05 (02) ◽  
pp. 463-479 ◽  
Author(s):  
P. Ryan ◽  
Y. Zhang ◽  
F. Liu ◽  
J. Gao ◽  
J.T. Bigger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Electronic Health Records ◽  
Real World ◽  
World Population ◽  
Health Records ◽  
Target Populations ◽  
Electronic Health

SummaryObjective: To improve the transparency of clinical trial generalizability and to illustrate the method using Type 2 diabetes as an example.Methods: Our data included 1,761 diabetes clinical trials and the electronic health records (EHR) of 26,120 patients with Type 2 diabetes who visited Columbia University Medical Center of New-York Presbyterian Hospital. The two populations were compared using the Generalizability Index for Study Traits (GIST) on the earliest diagnosis age and the mean hemoglobin A1c (HbA1c) values.Results: Greater than 70% of Type 2 diabetes studies allow patients with HbA1c measures between 7 and 10.5, but less than 40% of studies allow HbA1c<7 and fewer than 45% of studies allow HbA1c>10.5. In the real-world population, only 38% of patients had HbA1c between 7 and 10.5, with 12% having values above the range and 52% having HbA1c<7. The GIST for HbA1c was 0.51. Most studies adopted broad age value ranges, with the most common restrictions excluding patients >80 or <18 years. Most of the real-world population fell within this range, but 2% of patients were <18 at time of first diagnosis and 8% were >80. The GIST for age was 0.75. Conclusions: We contribute a scalable method to profile and compare aggregated clinical trial target populations with EHR patient populations. We demonstrate that Type 2 diabetes studies are more generalizable with regard to age than they are with regard to HbA1c. We found that the generalizability of age increased from Phase 1 to Phase 3 while the generalizability of HbA1c decreased during those same phases. This method can generalize to other medical conditions and other continuous or binary variables. We envision the potential use of EHR data for examining the generaliz-ability of clinical trials and for defining population-representative clinical trial eligibility criteria.Citation: Weng C, Li Y, Ryan P, Zhang Y, Liu F, Gao J, Bigger JT, Hripcsak G. A distribution-based method for assessing the differences between clinical trial target populations and patient populations in electronic health records. Appl Clin Inf 2014; 5: 463–479 http://dx.doi.org/10.4338/ACI-2013-12-RA-0105

scholarly journals Longitudinal clinical outcomes in a real-world population of patients with idiopathic pulmonary fibrosis: the PROOF registry

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wim A. Wuyts ◽  
Caroline Dahlqvist ◽  
Hans Slabbynck ◽  
Marc Schlesser ◽  
Natacha Gusbin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Clinical Outcomes ◽  
Real World ◽  
Lung Transplant ◽  
World Population ◽  
Duration Of Treatment

Abstract Background The PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry. Methods Patients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013–2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed. Results The PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months. Conclusions The PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower. Trial registration PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d’Éthique et de Recherche (CNER) N201309/03–12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.

Demographics, Treatment Patterns, Safety, and Real-World Effectiveness in Patients ≥70 Years of Age with Chronic Lymphocytic Leukemia Receiving Bendamustine with or without Rituximab,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3914-3914
Author(s):  
Kathryn S. Kolibaba ◽  
Avani D. Joshi ◽  
James A. Sterchele ◽  
Michael Forsyth ◽  
Erin Alwon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Real World ◽  
Progressive Disease ◽  
Lymphocytic Leukemia ◽  
Social Security Administration ◽  
Grade 3

Abstract Abstract 3914 Background Bendamustine is a unique, well-established alkylating agent with multifaceted actions leading to cancer cell death in several hematologic malignancies. In a phase 3 trial in treatment-naïve patients with chronic lymphocytic leukemia (CLL), rates of response and progression-free survival (PFS) were significantly superior to those for chlorambucil [Knauf WU et al. J Clin Oncol 2009;27:4378–84]. In vitro studies have found that the cytotoxic activity of bendamustine against CLL-derived cell lines is synergized by rituximab, an anti-CD20 monoclonal antibody [Demidem A et al. Cancer Biother Radiopharm 1997;12:177–86]. Older patients may demonstrate lower tolerance to chemoimmunotherapy [Foon KA & Hallek MJ. Leukemia 2010;24:500–11], and published clinical data on bendamustine-rituximab in CLL are scarce. Thus, this retrospective study sought to characterize a population of adults ≥70 years old with CLL receiving bendamustine with or without rituximab, describe patterns of care, assess data on real-world effectiveness outside of the controlled environment of clinical trials [Waldthaler C et al. Wien Klin Wochenschr 2011;123:269–275], and assess safety. Methods Records were extracted from US Oncology iKnowMed (iKM) record databases for all outpatients ≥70 years old with CLL (but no other tumor) and more than 1 visit recorded (but not enrolled in clinical trials) who received bendamustine between March 2008 and May 2010. Patients were classified as treatment-naïve or relapsed (including ≥ second-line therapy). To ascertain mortality, the iKM data were supplemented with vital-status data from the Social Security Administration Death Index. The overall response rate (ORR) included complete response (CR), nodal partial response (nPR), and partial response (PR). PFS was time from first bendamustine dose to progressive disease (change in line of therapy), relapse, or death from any cause. Data from patients who did not die, or had no progression and were lost to follow-up were censored. Results Among 91 patients, the mean (SD) initial age at beginning of first therapy was 77.4 (5.6) years, age at diagnosis was 70.3 (6.5) years, and 63.7% were male. Of the 16 (17.6%) treatment-naïve patients, 10 had received bendamustine monotherapy and 6 received bendamustine-rituximab. Of the 75 (82.4%) relapsed patients, 20 had received bendamustine monotherapy and 55 received bendamustine-rituximab. The observed ORR for treatment-naïve patients was 56.3% (n=9; 18.8% CR, 37.5% PR, and 0 nPR); 6.3% had progressive disease. For relapsed patients, the ORR was 58.7% (n=44; 13.3% CR, 44.0% PR, and 1.3% nPR); 24.0% had progressive disease. Among patients with data, median PFS for 16 treatment-naïve patients has not been reached (median follow-up 15.1 months); for 73 relapsed patients, PFS was 18.4 months. Kaplan-Meier estimates for PFS over time for each group are shown in the Figure. No unexpected toxicities were seen. The overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% for treatment-naïve patients and 25.3% for relapsed patients. Other grade 3/4 adverse events (AEs) included upper respiratory infection and abdominal pain in the relapsed group as well as rash and sepsis in both groups (n=1 each). The most frequent nonhematologic AEs (≥5%, any grade) were fatigue (33.0%), weight loss (11.0%), infection (9.9%; herpes zoster [n=2]; cryptococcal sepsis, Klebsiella sepsis, and pneumonia [n=1 each]), gastrointestinal (8.8%), fever (8.8%), pulmonary (6.6%), and rash (5.5%). o = data censored. Conclusions In this retrospective chart review of patients ≥70 years old with CLL, bendamustine, either alone or with rituximab, provided meaningful response rates and was generally well tolerated. The length of PFS of both treatment-naïve and relapsed patients was clinically meaningful. This research was sponsored by and conducted in collaboration with Cephalon, Inc., Frazer, PA. Disclosures: Sterchele: Cephalon, Inc.: Employment. Beygi:Cephalon, Inc.: Employment. Kennealey:Cephalon, Inc.: Employment.

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