scholarly journals Tyrosine Kinase Inhibitor (TKI) Switching Patterns during the First 12 Months in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients (Pts) in Routine Clinical Practice

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 937-937
Author(s):  
Stuart Goldberg ◽  
Mauricette Michallet ◽  
Rudiger Hehlmann ◽  
Teresa Zyczynski ◽  
Aimee Foreman ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Clinical Practice ◽  
Observational Study ◽  
Clinical Research ◽  
Research Funding ◽  
Acquired Resistance ◽  
Routine Clinical Practice ◽  
Site Conditions ◽  
Tki Discontinuation

Abstract Introduction:SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML pts in routine clinical practice receiving first-line (1L) imatinib (IM) prior to 2010 (retrospective) or 1L IM, dasatinib (DAS) or nilotinib (NIL) since 2010 (prospective) in the US and Europe. Methods: This analysis was designed to identify baseline characteristics associated with TKI switching in pts pooled from the prospective and retrospective cohorts. Pts were characterized as 'early switchers' (who discontinued 1L TKI and switched to a second-line [2L] TKI within 3 months of TKI initiation) or 'late switchers' (who discontinued 1L TKI and switched to a 2L TKI between 3 and 12 months after TKI initiation). A comparator group of 'non-switcher' pts did not discontinue 1L TKI within 12 months of TKI initiation; 'early non-switchers' did not switch 1L TKI within the first 3 months and 'late non-switchers' did not switch 1L TKI between 3 and 12 months after TKI initiation. Logistic regression analysis was used to identify factors associated with early vs. late switching (gender, age at diagnosis ≥65 years, 1L TKI, region, reason for discontinuation). Results: By March 07 2016, 1494 pts were enrolled at 197 sites in 7 countries. Within 12 months of initiating 1L TKI 238 pts (16%) had switched to 2L TKI. Of switchers, 31% and 69% were early and late, respectively. Of the overall cohort, 1189 pts were early non-switchers and 1146 were late non-switchers. Most early switchers received IM as 1L TKI (49%), followed by NIL (32%) and DAS (19%); most late switchers received IM (56%), followed by DAS (26%) and NIL (18%). Fewer early non-switchers than switchers received IM as 1L TKI (43%), followed by NIL (28%) and DAS (28%); fewer late non-switchers than switchers received IM (44%), followed by DAS (28%) and NIL (28%). Most switchers were female; a higher proportion of female switchers was early vs. late (63% vs. 52%, respectively). In comparison, 43% of pts in both non-switching groups were female. Median ages of early and late switchers were 54 (interquartile range [IQR]: 46-68) and 58 (IQR: 46-69) years, respectively; median ages of early and late non-switchers were 56 (IQR: 46-68) and 56 (IQR: 45-67) years, respectively. Logistic regression analysis showed that pts who switched due to intolerance had greater odds of switching early compared with those who switched due to resistance (odds ratio = 3.49; 95% confidence interval: 1.11-10.98; p=0.0323). Among the 238 pts who switched 1L TKI, the main reason for 1L TKI discontinuation was intolerance (early switchers: 76%; late switchers: 71%; Figure). The most common intolerances leading to changes in early and late switchers varied by 1L TKI. Most common for IM early switchers (n=26) was general disorders/administration site conditions (including fatigue, edema, pain) and skin/subcutaneous disorders; for IM late switchers (n=53), gastrointestinal (GI) disorders, general disorders/administration site conditions and skin/subcutaneous disorders. Most common for DAS early switchers (n=10) was GI disorders; for DAS late switchers (n=36), respiratory/thoracic/ mediastinal disorders. Most common for NIL early switchers (n=19) was GI disorders; for NIL late switchers (n=25), GI disorders, general disorders/administration site conditions and skin/subcutaneous disorders. TKI resistance less commonly contributed to 1L TKI discontinuation. Primary and acquired resistance were seen in higher proportions of late than early switchers (Figure). In late switchers, primary resistance was a more common reason for discontinuation in IM pts vs. DAS pts or NIL pts (22%, 5% and 4%, respectively). Acquired resistance was only reported as a reason for discontinuation in IM-treated pts (early switchers: 0.3%; late switchers: 11%). Conclusions: Of pts switching or discontinuing 1L TKI in the first 12 months of therapy, around one third switched within the first 3 months; compared with late switchers and non-switchers these pts were more likely to be younger and female. TKI intolerance was the main reason for switching and was significantly associated with early switching. Resistance was a less common reason for changing TKI therapy and was seen more frequently after 3 months and among pts treated with IM. More research is necessary to make definitive conclusions about comparisons between TKI groups, given the small numbers of pts in the TKI cohorts and the non-controlled nature of the trial. Disclosures Goldberg: COTA Inc: Employment; Novartis: Consultancy; Neostem: Equity Ownership; Pfizer: Honoraria; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Michallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Hehlmann:Bristol-Myers Squibb: Consultancy; Novartis: Research Funding; German CML-Group: Research Funding. Zyczynski:Bristol-Myers Squibb: Employment. Foreman:ICON Clinical Research: Employment. Calimlim:ICON Clinical Research: Employment. Paquette:Incyte: Consultancy, Honoraria; Novartis: Consultancy; Ariad: Consultancy. Gambacorti:Pfizer: Honoraria, Research Funding. Cortes:ARIAD: Consultancy, Research Funding; Bristol-Myers Squib: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Zagorska:Bristol-Myers Squibb: Employment. Rong:Bristol-Myers Squibb: Employment. Mauro:BMS: Consultancy; Ariad: Consultancy; Pfizer: Consultancy; Novartis: Consultancy.

scholarly journals Cardiovascular (CV)-Related Hospitalizations and Associated Costs Among US Patients in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) in Routine Clinical Practice

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4151-4151
Author(s):  
Stuart L. Goldberg ◽  
Michael J. Mauro ◽  
Jorge E. Cortes ◽  
Scott Justin Keating ◽  
Hitesh Bhandari ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Hospital Stay ◽  
Cardiac Failure ◽  
Research Funding ◽  
The United States ◽  
Routine Clinical Practice ◽  
Categorical Variables ◽  
The Us ◽  
Equity Ownership

Introduction: CV events in CP-CML can negatively impact clinical and survival outcomes (Coutinho et al, Clin Lymphoma Myeloma Leuk, 2017), and CV-related hospitalization (hosp.) is costly (Nicholson et al, Clinicoecon Outcomes Res, 2016; Naccarelli et al, Clin. Cardiol, 2010). Mounting evidence suggests the common CV risk factors observed in individuals over the age of 60 combined with tyrosine kinase inhibitor (TKI) therapy may contribute to CV events in patients (pts) with CP-CML (Moslehi & Deininger, J Clin Oncol, 2015; Aghel et al, Vasc Health Risk Manag, 2017). SIMPLICITY is an ongoing observational study of pts with CP-CML receiving first-line (1L) TKIs in routine clinical practice in Europe and the United States (US). Here, we assess CV-related hosp. rates for SIMPLICITY pts in the US receiving 1L imatinib (IM), dasatinib (DAS), or nilotinib (NIL), including the incidence of hospital admissions and length of hospital stay (LOS), and related costs. Methods: In US pts, CV-related hosp. during 1L IM, DAS, or NIL therapy were identified from review of the electronic case report forms completed by clinicians. To control for possible confounding effects of multiple lines of TKI therapy, pts were followed from 1L TKI initiation to 30-days post-treatment or TKI switch, whichever came first. CV-related hosp. rates and LOS during 1L therapy were evaluated on a per-1,000-pt-year (PY) basis. For each CV event, mean total hosp. costs were derived from the 2016 Healthcare Cost and Utilization Project-National (Nationwide) Inpatient Sample database, to which professional fees from peer-reviewed literature were added; the medical component of the Consumer Price Index was used to convert 2016 costs to 2018 US dollars ($). Statistical comparisons for continuous variables were made using t-tests and the Mann-Whitney U test, and chi-square test for categorical variables. Time to first CV-related hosp. was evaluated using Kaplan-Meier methods with the log-rank test. Results: In the US, 808 pts were receiving 1L IM (n=243), DAS (n=301), or NIL (n=264); median follow-up was approximately 4 years (48.7-51.3 months). Age, treatment center type, and baseline fatigue differed significantly between the groups (p<0.05); stratification of duration of therapy in pts showed significant differences between the three TKI cohorts (p=0.0005; Table 1). The number of pts with CV-related hosp. was similar between IM (11 [4.5%]) and DAS (13 [4.3%]) cohorts, but higher in the NIL cohort (21 [8.0%]), equating to 16.6, 14.1, and 25.0 CV-related hosp. per 1,000 PY, respectively. Total CV-related LOS was 81, 36, and 98 days for the IM, DAS, and NIL groups, respectively, translating to 122.4, 46.5, and 116.9 hospital stay days per 1,000 PY. Most frequently experienced CV events were cardiac failure (IM=3.0, DAS=3.2, NIL=7.2 [per 1,000 PY]) and hemorrhage (IM=7.6, DAS=2.2, NIL=4.8 [per 1,000 PY]); rate of the latter was lowest in the DAS group. The rate of myocardial infarction-related hosp. was 1.5 and 2.4 per 1,000 PY for IM and NIL cohorts, respectively. Most inpatient days were due to cardiac failure (IM=13.6, DAS=10.8, NIL=56.1 [per 1,000 PY]) and hemorrhage (IM=80.1, DAS=5.4, NIL=22.7 [per 1,000 PY]); for DAS and NIL, cardiac failure caused the most inpatient days, whereas CV-related hemorrhage was responsible for the most IM-related hospitalization days. 43.8% of the observed CV-related hosp. occurred within 12 months of 1L TKI initiation, with 68.8% occurring by the 18-month mark (Figure 1). No difference in time to first CV-related hosp. with 1L TKI was seen between cohorts (p=0.4644). CV-related hosp. costs were highest among pts receiving IM or NIL, approximately twice that of the DAS cohort. Estimates derived from the product of mean hosp. cost per CV event and the rate of hosp. showed total CV hosp. costs of $475,058, $264,053, and $495,688 per 1,000 PY for IM, DAS, and NIL, respectively. Conclusions: CV-related events and hosp. were reported among US pts with CP-CML receiving 1L TKIs; the majority of which occurred within 18 months of TKI initiation. The incidence of CV-related hosp. and LOS, and mean hosp. costs were lowest among pts receiving DAS compared with the IM and NIL cohorts. The potential for added morbidity, healthcare utilization, and associated costs due to CV complications must be considered when making decisions on the appropriate TKI for individual pts with CP-CML. Disclosures Goldberg: Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership; Bristol-Myers Squibb: Consultancy; COTA: Equity Ownership. Mauro:Bristol-Myers Squibb: Consultancy; Novartis Oncology: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; BiolineRx: Consultancy; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Keating:Bristol-Myers Squibb: Employment. Bhandari:SmartAnalyst India (Pvt.) Ltd.: Employment, Other: I am an employee of SmartAnalyst India (Pvt.) Ltd., a subsidiary of SmartAnalyst Inc. which was contracted by Bristol-Myers Squibb for carrying out this analysis. Chen:Bristol-Myers Squibb: Employment.

scholarly journals The association between hypoglycemia and glycemic variability in elderly patients with type 2 diabetes: a prospective observational study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Takahisa Handa ◽  
Akinobu Nakamura ◽  
Aika Miya ◽  
Hiroshi Nomoto ◽  
Hiraku Kameda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Observational Study ◽  
Elderly Patients ◽  
Prospective Observational Study ◽  
Multivariate Logistic Regression Analysis ◽  
Glycemic Variability ◽  
Multivariate Logistic Regression

Abstract Background This study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes. Methods We conducted a prospective observational study on 179 (71 female) Japanese outpatients with type 2 diabetes aged ≥ 65 years. The characteristics of the participants with TBR ≥ 1% were evaluated by multivariate logistic regression analysis. Receiver-operating characteristic (ROC) curve analyses of GV indices, comprising coefficient of variation (CV), standard deviation, and mean amplitude of glycemic excursions, were performed to identify the optimal index for the identification of patients with TBR ≥ 1%. Results In the multivariate logistic regression analysis, none of the clinical characteristics, including HbA1c and C-peptide index, were independent markers for TBR ≥ 1%, while all three GV indices showed significant associations with TBR ≥ 1%. Among the three GV indices, CV showed the best performance based on the area under the curve in the ROC curve analyses. Conclusions Among elderly patients with type 2 diabetes, CV reflected TBR ≥ 1% most appropriately among the GV indices examined. Trial registration UMIN-CTR: UMIN000029993. Registered 16 November 2017

scholarly journals A European Observational Study to Evaluate the Safety and the Effectiveness of Safinamide in Routine Clinical Practice: The SYNAPSES Trial

2021 ◽  
pp. 1-1
Author(s):  
Giovanni Abbruzzese ◽  
Jaime Kulisevsky ◽  
Bruno Bergmans ◽  
Juan C. Gomez-Esteban ◽  
Georg Kägi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Routine Clinical Practice

Abstract TMP2: Reduction of Time to Endovascular Treatment and Improved Outcomes After Ischemic Stroke in Routine Clinical Practice: Comparison of the MR CLEAN Registry First and Second Cohorts

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kars C Compagne ◽  
Manon Kappelhof ◽  
Robert-Jan B Goldhoorn ◽  
Charles B Majoie ◽  
Yvo B Roos ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Clinical Practice ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Functional Independence ◽  
Routine Clinical Practice ◽  
Anterior Circulation ◽  
Time To Treatment ◽  
Mr Clean

Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly time dependent, but whether active reduction of time to treatment leads to better outcome has not been demonstrated. We compared data of the two subsequent MR CLEAN Registry cohorts, comprising all patients in the Netherlands who had EVT for acute ischemic stroke from 2014-2017, for a trend in time to treatment and its association with outcome. Methods: We compared workflow, successful reperfusion (eTICI 2B-3), NIHSS at 24h, functional outcome (mRS) at 90 days, occurrence of symptomatic intracranial hemorrhage (sICH) and mortality in patients with ischemic stroke and a proximal intracranial occlusion in the anterior circulation included in the second cohort of the Registry (June 2016-November 2017; n = 1779) to those in patients included in the first cohort (March 2014-June 2016; n = 1526) using logistic regression. Results: Baseline NIHSS was 16 in both cohorts. Times from onset-to-groin and onset-to-reperfusion were shorter in the second cohort than in the first (185 versus 210 minutes; p<0.01 and 238 versus 270 minutes; p<0.01, respectively) (Figure 1). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 58%; p<0.01). Rates of sICH and mortality did not differ (5.9% versus 5.7%; p=0.94 and 29% versus 29%; p=0.60). However, follow-up NIHSS was lower (median 10 versus 11; p<0.001) and more patients achieved functional independence at 90 days (42.6% versus 38.9%; p = 0.012) in the second cohort (Figure 1). In a logistic regression model, the difference in good outcome between the two cohorts (aOR 1.27; 95%CI 1.08-1.50) was reduced after additional adjustment for time to reperfusion (aOR 1.15; 95%CI 0.96-1.36) as well as successful reperfusion (aOR 1.16; 95%CI 0.95-1.41). Discussion: Our data show that outcomes after EVT in routine clinical practice are improving, likely attributable to improved workflow and experience.

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