Employee Of Analysis Group Research Articles

Dose-Response Relationship Between Long-Term Systemic Corticosteroid Use and Related Complications in Patients with Severe Asthma.

Systemic corticosteroids are a leading cause of drug-related complications, yet little has been done to quantify the dose-response relationship between systemic corticosteroid exposure and complications in patients with severe asthma. To (a) evaluate the risk of developing systemic corticosteroid-related complications by corticosteroid exposure in severe asthma and (b) quantify the associated health care resource utilization and costs. This is a retrospective study using administrative claims data from a large commercial database between 2003 and 2014. Multivariate generalized estimating equation models were used to compare corticosteroid-related complications in patients continuously exposed to at least 5 mg of prednisone or equivalent for ≥ 6 months with a 1:1 ratio of propensity score-matched patients with asthma who did not use corticosteroids. A total of 12,697 corticosteroid users and as many matched nonusers were identified. The odds of developing associated complications increased significantly in a dose-dependent manner with systemic corticosteroid exposure: odds ratios were 2.50, 2.95, and 3.32 (P values <0.05) for low (defined as < 5 mg/day), medium (≥ 5-10 mg/day), and high (>10 mg/day) exposure, respectively, relative to no exposure. Health care resource utilization increased significantly with levels of systemic corticosteroid exposure. Hence, incidence rate ratios for inpatient visits with low, medium, and high exposure relative to none were estimated to be 1.86, 2.40, and 3.37, respectively (P < 0.05). A significant dose-response relationship was found between the long-term use of systemic corticosteroids and the risk of developing systemic corticosteroid-related complications in patients with severe asthma, resulting in increased burden and costs on the health care system that intensified with systemic corticosteroid exposure. Funding for this study was provided by GlaxoSmithKline, Study number H0-15-15930, to Analysis Group for the conduct of this study. Lefebvre, Duh, and Gozalo are employees of Analysis Group, a contract research organization that has received research grants from GlaxoSmithKline. Robitaille was employed by Analysis Group at the time of this study. Yancey, Forshag, Lin, and Albers are employees of GlaxoSmithKline and own company stock. Dalal and Ortega were employed by GlaxoSmithKline at the time of this study. Lefebvre had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Additionally, all listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Study concept and design were contributed by Dalal, Duh, Albers, Yancey, Ortega, Forshag, and Lefebvre. Data acquisition was by Dalal, Gozalo, Robitaille, Forshag, and Lefebvre and was analyzed and interpreted by Dalal, Gozalo, Robitaille, Albers, Yancey, Ortega, Forshag, and Lefebvre. The manuscript was drafted and approved by Dalal, Duh, Gozalo, Robitaille, Albers, Yancey, Ortega, Forshag, Lin, and Lefebvre.

The direct and indirect costs associated with endometriosis: a systematic literature review.

What is the economic burden of endometriosis? The identified studies indicate that there is a significant economic burden associated with endometriosis, as observed by both direct and indirect costs. Two previous systematic literature reviews suggested that there were considerable direct costs associated with endometriosis and there was a general lack of measurement of indirect costs. We performed a systematic literature review. MEDLINE and EMBASE databases from 2000 to 2013 were searched. The literature search was limited to human studies of patients with endometriosis. Papers in languages other than English were excluded. Studies reporting direct or indirect costs among patients with endometriosis were considered for inclusion. Direct costs included inpatient, outpatient, surgery, drug and other healthcare service cost. Indirect costs were related to absenteeism and presenteeism (lost productivity at work). After evaluating the 1396 articles in the search results, 12 primary studies that reported direct or indirect costs associated with endometriosis were identified and included in the data extraction. Three of the studies were conducted in the USA, one study each was conducted in Austria, Belgium, Brazil, Canada, Finland, Germany and Italy, and two studies included data from 10 countries. Significant variability was observed in the reviewed studies in methodology, including data source, cost components considered and study perspective. Estimates of total direct costs ranged from $1109 per patient per year in Canada to $12 118 per patient per year in the USA. Indirect costs of endometriosis ranged from $3314 per patient per year in Austria to $15 737 per patient per year in the USA. The studies identified in the systematic literature review varied greatly by study methodology as well as by country owing to different healthcare systems and costs of healthcare services, which contributed to large variations in the direct and indirect cost estimates. A majority of the studies we found were published after the periods covered in the prior systematic literature reviews, which provided substantial contributions to an understanding of the economic burden of endometriosis, especially in the area of indirect costs. The long-term burden of endometriosis following diagnosis is still under-studied, which is a concern given the chronic nature of the disease and the substantial recurrence of endometriosis symptoms. This study was funded by AbbVie, which also develops the oral GnRH antagonist elagolix (in collaboration with Neurocrine Biosciences) for the management of endometriosis and uterine fibroids. A.M.S. is an employee of AbbVie and currently owns AbbVie stocks. H.Y., E.X.D. and C.K. are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. C.W. is a Clinical Professor at the Department Obstetrics and Gynecology at Georgetown University in Washington, DC, USA and has served in a consulting role to AbbVie for this project.

PCN43 - A Cost Comparison of Split-Dose Reduced-Volume oral Sulfate Solution (OSS) And Polyethylene Glycol With Electrolytes Solution (Peg-Els)

Presented at the ISPOR 20th Annual International Meeting, Philadelphia, PA, USA, May 16–20, 2015 Funding and other disclosures statement: This research was funded by Braintree Laboratories, Inc. Mark Cleveland is an employee of Braintree Laboratories, Inc. Francis A. Farraye is a research consultant for Braintree Laboratories. Romaine Campbell, Lynn Huynh, and Mihran Yenikomshian are employees of Analysis Group, Inc., which received research grant from Braintree Laboratories, Inc. *During the cost model’s development, Sander Yermakov and Matthew Davis were employees of Analysis Group, Inc. BACKGROUND

Twelve-Month Cost per Responder (CPR) Analysis of Nilotinib and Dasatinib As Front-Line Therapy in Patients with Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

Introduction: Nilotinib and dasatinib, two second-generation tyrosine kinase inhibitors (TKIs), have been associated with higher rates of molecular response compared to imatinib in the treatment of newly diagnosed CML-CP patients based on the ENESTnd and DASISION trials. A published indirect comparison study of efficacy outcomes between nilotinib and dasatinib showed that nilotinib had significantly higher rates of molecular response by 12 months compared to dasatinib: major molecular response (MMR; defined as BCR/ABL1 level ≤0.1% on International Scale [IS]): 56.1% vs. 45.9%; MR4.0 (BCR/ABL1 level ≤0.01% on IS): 20.6% vs.12.0%; and MR4.5 (BCR/ABL1 level ≤0.0032% on IS): 10.2% vs. 3.1% for nilotinib and dasatinib, respectively. However, little is known about the costs associated with achieving molecular response. This study estimated and compared the CPR for the first 12 months of nilotinib and dasatinib for the treatment of Ph+ CML-CP in a front-line setting from a US payer’s perspective.Methods: A 12 month CPR model of nilotinib and dasatinib was constructed, where MMR by 12 months was used to define a responder and the rates were from the published indirect comparison study. The two model cost components were 12 month treatment costs and treatment-related grade 3/4 adverse event (AE) costs. Treatment costs were estimated based on drug price (wholesale acquisition cost), median dose and discontinuation rate. Drug prices by dose were extracted from the Red Book Online®. Median doses and discontinuation rates were from the ENESTnd, DASISION and the 2nd-line trials of nilotinib and dasatinib. Discontinuation was assumed to occur at a constant rate over the 12 months. Patients who discontinued the initial treatment were assumed to switch to the other second-generation TKI and remain on this for the rest of the first year. No patient was assumed to die within the first 12 months, i.e. no patients discontinued due to death. AE costs were estimated based on AE rates and the costs of treating the AE: treatment-related rates of grade 3/4 AEs were obtained from the clinical trials and direct medical costs were obtained from published literature. Because the definition of AEs may differ across the two trials, AE rates were adjusted relative to the AE rates observed in the imatinib arms of the two trials. The 12 month CPR for each treatment was calculated as the sum of the 1st-line treatment costs, the 2nd-line treatment costs (after a switch), and the grade 3/4 AE costs incurred by responders and non-responders, divided by the MMR rate. All costs were presented in 2014 USD. One-way sensitivity analyses varying the response definition (including MR4.0 and MR4.5) and AE costs were conducted.Results: The 12 month CPR was $202,840 for nilotinib and $248,919 for dasatinib (difference=$46,079; p <0.05). Costs of neutropenia, thrombocytopenia and anemia were the driving factor behind AE costs; these costs in the nilotinib arm were about half (53%) of the costs for of these AEs in the dasatinib arm. In one-way sensitivity analyses with responders defined based on MR4.0 and MR4.5, the differences in CPR between the two drugs were even greater: CPR for nilotinib was 42% and 70% (both p<0.05) lower than that for dasatinib for MR4.0 and MR4.5, respectively. In one-way sensitivity analyses that varied the costs of AEs to their lower and upper bounds, CPR ranged from $201,277 to $217,298 for nilotinib and $245,245 to $280,568 for dasatnib. Nilotinib’s CPR was 17.9% and 22.6% (both p<0.05) lower than dasatinib’s CPR for the low and high AE cost estimates, respectively.Conclusion: This analysis demonstrates that, compared to dasatinib, front-line therapy with nilotinib is associated with a lower CPR during the first 12 months in patients with newly diagnosed CML-CP from a US payer’s perspectiveAbstract 1304. Table 1CPR ResultsResponse Rates*Treatment CostsGrade 3 / 4 AE CostsCPRCPR Difference(Nilo – Dasa)NiloDasaNiloDasaNiloDasaNiloDasaMMR56.1%45.9%$112,024$110,901$1,769$3,353$202,840 $248,919 -$46,079 p <0.05MR4.020.6%12.0%$552,394$952,117-$399,723 p <0.05MR4.510.2%3.1%$1,115,619$3,685,613 -$2,569,994 p <0.05Nilo: Nilotinib; Dasa: Dasatinib*Signorovitch, J.E., et al. One-year and longer-term molecular responses to nilotinib and dasatinib for newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison. Abstract presented at American Society for Clinical Oncology, Chicago, May 30-June 3, 2014. DisclosuresGuerin:Novartis Pharmaceuticals Corporation: Consultancy, I am an employee of Analysis Group, Inc., which received consultancy fees from Novartis Other. Revol:Novartis Pharmaceuticals Corporation: Consultancy, I am an employee of Analysis Group, Inc., which received consultancy fees from Novartis Other. Ramanakumar:Novartis Pharmaceuticals Corporation: Consultancy, I am an employee of Analysis Group, Inc., which received consultancy fees from Novartis Other. Foster:Novartis Pharmaceuticals Corporation: Consultancy, I am an employee of Analysis Group, Inc., which received consultancy fees from Novartis Other. Wu:Novartis Pharmaceuticals Corporation: Consultancy, I am an employee of Analysis Group, Inc., which received consultancy fees from Novartis Other. Mhatre:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Employment, Stock options Other.

Comparison of Survival Rates, Healthcare Resource Use and Costs of Elderly Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As Second-Line Therapy

Comparison of Survival Rates, Healthcare Resource Use and Costs of Elderly Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As Second-Line Therapy

A Retrospective Analysis of Treatment Patterns in Elderly Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As Second-Line Therapy after Imatinib

Introduction: Dasatinib and nilotinib are second-generation tyrosine kinase inhibitors (TKIs) originally approved as second-line treatment for patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase resistant or intolerant to imatinib. Despite the fact that one half of patients with CML are ≥65 years of age, elderly patients are often under-recruited in clinical trials and there are few studies that focus on these often medically complex patients. This study aimed to compare treatment patterns of elderly CML patients initiating dasatinib vs nilotinib as second-line TKI therapy after imatinib therapy in a real-world setting. Methods: Elderly Medicare beneficiaries (≥65 years old) with ≥2 CML diagnoses who initiated dasatinib or nilotinib following prior treatment with imatinib were identified in the Medicare Research Identifiable Files (RIF) from 2006 to 2012. Selected patients were continuously covered by Part A (i.e., institutional claims), Part B (i.e., non-institutional claims), and Part D (i.e., drug events) for ≥6 months before and ≥1 month after the second-line TKI therapy initiation date (i.e., index date). Patients were excluded from the study if they were enrolled in a clinical trial, had a stem-cell transplant, or received chemotherapy (except hydroxyurea) within the 6 months before the index date (i.e., baseline period). Patients were classified as dasatinib users or nilotinib users based on the second-line TKI therapy. Dose decreases and increases, defined as a dose change of ≥20mg for dasatinib and ≥100mg for nilotinib compared to the initial dose, were measured from the index date up to the end of follow-up or treatment discontinuation. Treatment adherence was measured using the proportion of days covered (PDC) during the 6- and 12-month periods following the index date and among patients with continuous insurance coverage during these periods. Treatment persistence, measured between the index date and the end of follow-up, included time to treatment discontinuation (i.e., a treatment gap of ≥30 consecutive days) or switch to another TKI. Multivariate regression analyses were used to test for statistical significance while adjusting for potential confounding factors. Results: Of the 659 patients that met the sample selection criteria, 379 were dasatinib users and 280 were nilotinib users. The average age was 76 years (inter-quartile range 70 – 81) and 62% were female. After the index date, 88% of selected patients were observed for ≥6 months and 73% for ≥12 months. The average patient follow-up was 24 months (median=22 months). Dasatinib users were more likely to start on the recommended dose compared to nilotinib users (74% vs 53%; p Conclusion: There are little data available on treatment patterns of elderly CML patients. This study suggests that it is hard to determine the right starting dose of drug in elderly patients receiving a second generation TKI following treatment with imatinib. Interestingly, those receiving nilotinib had fewer dose adjustments (decreases or increases) and were more persistent (fewer discontinuation and switching) compared to those receiving dasatinib despite having similar levels of adherence over the first 6- and 12-month periods following the treatment initiation. Studies which focus on patients with elderly CML may help to provide better treatment guidelines for this important population. Disclosures Liu:Jun Liu is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Latremouille-Viau:Dominick Latremouille-Viau is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Zhou:Zhou Zhou is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Guerin:Annie Guerin is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Fernandez:Daniel Fernandez is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Yi:Dingdong Yi is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Wang:Xufei Wang is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Wu:Eric Q. Wu is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Mhatre:Novartis Pharmaceuticals Corporation: Employment. Keir:Novartis: Employment, Equity Ownership. Chen:Novartis Pharmaceuticals Corporation: Employment; Novartis: stock options Other.

Predictors of Treatment (Tx) Response and Progression in Braf V600E Metastatic Melanoma (Mm) Patients (Pts) with Brain Metastases (Bm) Receiving Vemurafenib (Vem) in a Real-World Setting

ABSTRACT Aim: mM pts with BM are associated with poor prognosis. Selective BRAF inhibitors may have a significant role in the tx of BM but data are limited. This study investigates predictors of intracranial tx response and intracranial progression among BRAFV600E mM pts with BM receiving vem in a real-word setting. Methods: Demographic and clinical characteristics, disease progression status, and tx response data were collected from a chart review by a panel of US oncologists on 283 BRAFV600E mM pts with active BM receiving vem. Predictors of intracranial tx response (complete response [CR] or partial response [PR]) and intracranial disease progression while on vem were identified using logistic regression models. Results: At vem initiation, mean age was 57 years, 61% of pts were male, and 68% had ECOG 0-1. Median follow-up time after vem initiation was 5.7 months. 53% of pts discontinued vem tx and 7% of pts had a vem dose reduction. While on vem, 48% of pts achieved intracranial CR/PR and 46% of pts achieved extracranial CR/PR. Intracranial disease progression occurred in 28% of pts while on vem. Predictors of intracranial CR/PR were corticosteroid use while on vem and the use of vem as 1st line tx after BM diagnosis (Table). Pts with larger number and size of BM before vem were less likely to achieve intracranial CR/PR. Predictors of disease progression were progressive extracranial disease before vem, larger number and size of BM before vem, and extent of extracranial metastasic disease before vem. The use of local tx before vem was associated with a reduced risk of intracranial progression. Conclusions: In real-world practice, 48% pts achieved intracranial CR/PR when treated with vem. Predictors of tx response were lower size and number of BM, earlier use of vem, and corticosteroid use. Predictors of intracranial progression were larger size and number of BM, progressive extracranial disease before vem, extent of extracranial metastasic disease, and no local tx before vem. Prospective data on tx outcomes are warranted in this population with high unmet need. Odds ratio (95% CI) Predictors of Intracranial CR or PR Concomitant use of corticosteroids (ref: no use of corticosteroids) 3.7 (1.9; 7.0) Number of BM (ref: ≤ 3 BM) ≥ 4 BM 0.3 (0.1; 0.6) Diameter of the largest BM (ref: 5-10mm 0.2 (0.1; 0.7) ≥ 10mm 0.8 (0.3; 1.9) Vem as 1st line after BM diagnosis (ref: vem initiated later lines) 4.4 (1.4; 13.3) Predictors of Intracranial Progression Progressive extracranial metastatic disease before vem initiation (ref: stable/regressive) 4.8 (2.3; 10.1) Local treatment for BM (ref: no local treatments) 0.4 (0.2; 0.9) Number of BM (ref: ≤ 1 BM) 2-4 BM 1.5 (0.6; 3.6) ≥ 5 BM 8.2 (2.3; 28.8) Number of sites of extracranial metastases (ref: ≤ 1 site) 2 sites 3.7 (1.6; 8.8) ≥ 3 sites 1.9 (0.8; 4.8) Diameter of the largest BM (ref: 5-10mm 7.8 (2.1; 29.1) ≥ 10mm 3.3 (0.9; 11.7) Disclosure: G. Gibney: Geoffrey Thomas Gibney is an employee of the Moffitt Cancer Center and a consultant for Roche/Genentch; G. Gauthier: Genevieve Gauthier is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; C. Ayas: Charles Ayas is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; P. Galebach: Phil Galebach is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; E. Wu: Eric Wu is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; Y.M. Yim: Yeun Mi Yim is an employee of Genentech Inc. and hold stock ownership of Roche; S.S. Abhyankar: Sarang S. Abhyankar is an employee of Genentech Inc. and hold stock ownership of Roche; C. Reyes: Carolina M. Reyes is an employee of Genentech Inc. and hold stock ownership of Roche; A. Guerin: Annie Guerin is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply.

Impact Of Low-Grade Adverse Events (AEs) On Health-Related Quality Of Life (HRQoL) In Adult Patients With Newly Diagnosed Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia In Chronic Phase (Ph+ CML-CP) From The Enestnd Trial: 48-Month Follow-Up

BackgroundIn the randomized, phase 3 ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) trial, the superior efficacy of nilotinib (NI) compared with imatinib (IM) has been firmly established in patients with newly diagnosed Ph+ CML-CP. Based on the 36 month ENESTnd data, both NI and IM demonstrated good safety and AE profiles, with low-grade AEs (grades 1/2) being reported more frequently than grade 3/4 AEs. AEs, even mild and moderate in nature, may negatively impact HRQoL. This post-hoc analysis evaluated the association between low-grade AEs and HRQoL using the 48-month update of ENESTnd. Methods846 newly diagnosed Ph+ CML-CP patients were randomized to NI 300 mg BID (n = 282), NI 400 mg BID (n =281), or IM 400 mg QD (n = 283). HRQoL was assessed using the Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) and the Short Form 36 Health Survey (SF-36). Derived HRQoL scores included FACT-Leu Total (FLT), SF-36 mental component summary (MCS) and SF-36 physical component summary (PCS). Questionnaires were scheduled to be administered at enrollment and the end of 3, 12, 24, 36 and 48 months or at early discontinuation. Low-grade AEs were classified based on the 26 system organ classes (SOCs) and assessed during a 7-day and 28-day observation period prior to each administration date of FACT-Leu and SF-36 questionnaires, respectively, which corresponds to the periods over which these HRQoL outcomes were measured. Only AEs with a prevalence ≥1% during the observation period were analyzed. The change in HRQoL outcomes from baseline was compared between patients with low-grade AEs and those without any AEs during the observation period (excluding patients with grade 3/4 AEs) using linear mixed effects models, adjusting for potential confounders. Subsequently, adjusted Poisson regression models were used to compare frequencies of low-grade AEs that were found to significantly impact HRQoL over the course of 48 months among the three treatment arms. ResultsOverall, the occurrence of gastrointestinal (GI) (e.g. nausea, diarrhea), general (e.g. fatigue, peripheral edema), musculoskeletal (e.g. muscle spasms, arthralgia) and psychiatric disorders (e.g. insomnia, anxiety) had a statistically significant negative impact on change in HRQoL from baseline (Table 1). Both NI treatment arms had a significantly lower incidence of GI and musculoskeletal disorders compared with IM (Table 2). ConclusionsSome low-grade AEs impaired HRQoL in patients treated with NI or IM. These AEs were less frequent in patients treated with NI.1. Linear mixed effect models adjusted for demographics, prior treatment, clinical measures and other low grade AEs with < 1% prevalence during the observation period combined together.2. “-“ indicates that the AE SOC prevalence was < 1% during the observation period.3. N represents the number of individual HRQoL assessments across all patients included in the analysis.1. Poisson regression models adjusted for demographics, prior treatment and clinical measures. Disclosures:Chen:Novartis: Employment, Equity Ownership. Guerin:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Marynchenko:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Ionescu-Ittu:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Hiscock:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Nitulescu:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Pooja:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Hsu:Novartis: Employment, Intern Other. Keir:Novartis: Employment, Equity Ownership. Wu:Novartis Pharmaceuticals: Consultancy, employee of Analysis Group Inc., which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Impact of the FDA Safety Communication on Prescription Trends of Clopidogrel in Combination with Proton Pump Inhibitors: Presidential Poster

Purpose: In 2009, FDA's safety communication warned that omeprazole reduced the antithrombotic effect of clopidogrel by almost half. The aim of this study was to assess the impact of the FDA safety communication on prescription trends of clopidogrel in combination with PPIs. Methods: Adult clopidogrel users were identified from a large retrospective U.S. claims database. Rates of combination therapy were estimated in 6-month intervals between Jan 2006 to Mar 2012 for patients with ≥1 clopidogrel prescription fill and continuous plan enrollment for the previous and current 6-month intervals. Combination therapy was defined as clopidogrel-PPI use for ≥30 consecutive days during the interval. The probability of combination therapy pre- and post-safety communication period (11/17/2009) was compared. Results: 327,368 pre-safety and 277,821 post-safety communication patient intervals were identified. On average, 34.1% of patients in the pre-period and 15.9% in the post-period used a PPI-clopidogrel combination therapy; the probability of combination use fell almost two thirds (odds ratio [OR] 0.36; p<0.001; Figure 1). Among patients using combination therapy, the percentage using omeprazole changed insignificantly (33.9% vs. 34.39%), the percentage using esomeprazole decreased (48.7% vs. 32.9%), and the percentage of those using pantoprazole increased the most (9.9% vs. 24.0%). Trends were similar for all and newly treated patients, regardless of indication and physician specialty. But, among new combination therapy patients, the percentage using omeprazole increased (34.3% vs. 38.2%; p<0.001).FigureConclusion: The FDA safety communication resulted in an overall decrease of PPI use by patients using clopidogrel. However, among patients receiving combination therapy, about one third still used omeprazole and a similar proportion still used esomeprazole after the FDA safety communication. Disclosure - Annie Guerin, senior economist, is an employee of Analysis Group, inc, which has received consulting fees from Takeda Pharmaceuticals Valerie Carter, economist, is an employee of Analysis Group, inc, which has received consulting fees from Takeda Pharmaceuticals Eric Q Wu, Managing Principal, is an employee of Analysis Group, inc, which has received consulting fees from Takeda Pharmaceuticals Reema Moody, Associate Director, is an employee of Takeda Pharmaceuticals International Inc. This research was supported by an industry grant from Takeda Pharmaceuticals.

Frequency of Molecular Monitoring Correlates with Long Term Outcomes in Chronic Phase Chronic Myelogenous Leukemia Treated with First-Line Imatinib: Results of a Community Survey

AbstractAbstract 1685 Background:Molecular monitoring is recognized as an important part of evaluating treatment response in Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase (Ph+ CML-CP). The latest guidelines from the National Comprehensive Cancer Network (NCCN) recommend quantitative polymerase chain reaction (QPCR) testing in the first 3 months with a goal of <10% Bcr-Abl transcripts using the international scale (IS), and then testing every 3 months to achieve at some point and maintain a 3 log reduction in transcripts (Major Molecular Response). Regular molecular monitoring provides an opportunity to detect resistance or adherence problems early. However, it remains unknown how patterns of use of molecular monitoring impact long term outcomes in non-research community settings. Methods:Community physicians who treat CML patients were invited to retrospectively submit information on Ph+ CML-CP patients in their practice who were ≥18 years old when started on first-line imatinib between 2006–2011 and who had ≥6 months of follow-up. Patients enrolled in clinical trials were excluded. Clinical characteristics at treatment initiation were collected. For each 3 month period after treatment initiation while the patient was on tyrosine kinase inhibitor (TKI) therapy, information was collected on molecular monitoring performed to assess treatment response. Information on death and progression to accelerated phase or blast crisis was collected over the entire follow-up period. Patients were grouped by the average number of QPCR tests received on TKI therapy (scaled to rate per year): the 0 tests group if they never had a QPCR test; the 1–2 tests group if they had on average more than 0 but 2 or less QPCR tests/year; and the 3–4 tests group if they had on average more than 2 but 4 or less QPCR test/year. Progression, mortality, and combined progression/mortality rates were reported for each group. In addition, Cox proportional hazards models were used to test the association between progression and progression-free survival and the average number of QPCR tests per year, controlling for the average number of cytogenetic tests per year, and for potential confounders including age, race, initial imatinib dose, Sokal score, and enlarged spleen at diagnosis. Results were reported as hazard ratios (HR) with 95% confidence intervals (CI). Results:38 hematologists and oncologists from community practices throughout the US submitted information on 402 patients initiated on first-line imatinib. Patients were followed retrospectively for a median duration of 36 months. Of these, 52 (13%) had no molecular monitoring, 164 (41%) had 1–2 tests/year, and the remaining 186 (46%) had 3–4 tests/year. The figure below shows progression, mortality, and progression/mortality by frequency of molecular testing. The progression/mortality rates tended to decrease with the number of tests received. Adjusting for cytogenetic testing frequency and potential confounders aside from the Sokal score, a higher average number of QPCR tests per year was significantly associated with a lower rate of progression and longer progression-free survival. Each additional QPCR test per year significantly decreased the risk of progression by 45% (HR=0.55; CI [0.35, 0.87], p=0.011), and progression/mortality by 48% (HR=0.52; CI [0.35, 0.79], p=0.002]. Since 48% of patients did not have a reported Sokal score at diagnosis, a separate analysis was done to also adjust for the Sokal score among those without missing data, with nearly identical results. Conclusions:Ph+ CML-CP patients who underwent QPCR testing every 3–4 months experienced decreased progression and longer progression-free survival compared to those patients monitored less frequently, with the impact of molecular monitoring being independent of the frequency of cytogenetic testing. It is possible that molecular monitoring identifies impending treatment failure earlier and enables adjustment of therapy before hematologic and cytogenetic failure occur. This analysis underscores the value of molecular monitoring every 3 months for Ph+ CML-CP patients on TKI therapy and also demonstrates that a significant number of Ph+ CML-CP patients are not undergoing QPCR at the frequencies recommended in published guidelines. Additional community based education on CML monitoring is needed to assure optimal outcomes. [Display omitted] Disclosures:Goldberg:Novartis Oncology: Research Funding, Speakers Bureau. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Ericson:Novartis Pharmaceuticals Corp: Employment, Own stock in Novartis Other. Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Liu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Kaminsky:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Comparison of Disease Outcomes for Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy.

AbstractAbstract 2796 Background:Nilotinib and dasatinib are two tyrosine kinase inhibitors (TKIs) commonly used for the treatment of patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. Both TKIs have been shown to be more potent than imatinib. However, no head-to-head clinical trials have been conducted comparing the efficacy of nilotinib to dasatinib as 2nd-line therapy for CML-CP patients resistant or intolerant to imatinib. This study compared disease outcomes of patients treated in the community who were switched from imatinib to 2nd-line nilotinib or dasatinib. Methods:Through an online chart abstraction form, participating community physicians submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to 2nd-line nilotinib or dasatinib with at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients in each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information was collected on demographics, clinical characteristics, cytogenetic response, progression to accelerated phase or blast crisis, and death from any cause. Documented complete cytogenetic response (CCyR) at a particular time point was defined as 0% Philadelphia chromosome positive cells on cytogenetic testing; patients with missing tests at that time point were counted as non-responders. Disease progression to accelerated phase or blast crisis, progression-free survival, and overall survival were compared using multivariate Cox proportional hazards models, adjusting for potential confounding factors, including patient demographics and clinical characteristics at the time the patient switched to a 2nd-line TKI. Results:122 hematologists and oncologists provided information on 597 patients, including 301 patients on nilotinib and 296 patients on dasatinib. The median follow-up was 11 months for nilotinib patients and 10 months for dasatinib patients. Age, sex, race, comorbidities, and other clinical characteristics were similar for both groups, except that nilotinib patients were more likely than dasatinib patients to have switched due to secondary imatinib resistance (p=0.047) and were less likely to have switched due to imatinib intolerance (p=0.024). Nilotinib patients had similar rates of documented CCyR compared to dasatinib patients at 12 months (37% vs. 35%, p=0.54), 24 months (42% vs. 40%, p=0.62), and 36 months (44% vs. 44%, p=0.95) following the switch. However, nilotinib patients had lower risk of progression (p=0.004), higher progression free survival (p=0.023) and a trend towards prolonged overall survival (p=0.067), adjusting for potential confounders. The table below summarizes these results. Conclusions:Among patients with CML-CP switched to nilotinib or dasatinib for 2nd-line therapy, nilotinib patients had significantly lower rates of progression and longer progression-free survival compared to dasatinib patients.OutcomeNilotinib EventsDasatinib EventsUnadjusted Hazard RatioP-valueAdjusted Hazard RatioP-value(n=301)(n=296)Progression5 (1.7)13 (4.4)0.39 (0.14–1.09)0.0720.15 (0.04–0.55)0.004Progression-free Survival286 (95.0)269 (90.9)1.81 (0.96–3.40)0.0672.14 (1.11–4.12)0.023Overall Survival291 (96.7)279 (94.3)1.71 (0.78–3.75)0.1772.13 (0.95–4.78)0.067 Disclosures:Griffin:Novartis: Consultancy, Research Funding. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Comparison of Treatment Changes for Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched From Imatinib to Nilotinib or Dasatinib As Second-Line Therapy

AbstractAbstract 4443 Background:Nilotinib and dasatinib are two therapies approved by the US Food and Drug Administration for pts with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase (Ph+ CML-CP) who are resistant or intolerant to 1st-line imatinib. Although these therapies were shown to be generally effective and tolerable, sometimes they are not, requiring treatment changes (e.g., discontinuation, dose modification, and drug holidays). To date, no head-to-head study has been conducted to compare treatment changes between 2nd-line nilotinib and dasatinibin clinical practice. Methods:Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on Ph+ CML-CP pts ≥ 18 years old who switched after 10/28/2007 from imatinib to 2nd-line nilotinib or dasatinibwith at least 30 days of follow-up. When multiple pts met the selection criteria, pts were selected randomly by physicians. Pts enrolled in clinical trials or with concurrent malignancies were excluded. Information was collected on clinical characteristics and therapy changes in 2nd-line treatment, including dose modification (increase or decrease), drug holiday, and discontinuation of current therapy with or without switch to a 3rd-line therapy. Reasons for therapy changes were also collected, and treatment changes were classified as due to (1) lack of effectiveness if reasons included progression to accelerated phase or blast crisis, failure to achieve satisfactory response, or loss of satisfactory response; (2) intolerance if reasons included adverse events; (3) other reasons, including non-adherence, vacation, pregnancy, or economic reasons. Rates of treatment changes were compared between treatment groups using chi-square tests. Results:122 hematologists and oncologists provided information on 597 pts (301 nilotinib pts and 296 dasatinib pts). The median follow-up was 11 months (range 1–54 months) for pts on nilotinib and 10 months (range 1–56 months) for those on dasatinib. The two groups had similar age, sex, race, and comorbidities. Overall, treatment change was infrequent for both nilotinib and dasatinib patients (10% vs. 13%, p=0.40), but nilotinib pts had significantly fewer dose increases vs. dasatinib pts (0.0% vs. 1.4%, p=0.04), and they tended to have fewer drug holidays (1.7% vs. 4.4%, p=0.05). When treatment changes were classified by reason for change, nilotinib pts were less likely to change treatment due to lack of effectiveness vs. dasatinib pts (2.0% vs. 5.1%, p=0.04). Further, among pts who discontinued, fewer nilotinib pts discontinued due to lack of effectiveness (29% vs. 61%, p=0.03). Nilotinib and dasatinib pts had similar rates of treatment changes due to intolerance or other reasons, except for drug holiday, where nilotinib pts had fewer events than dasatinibpts (0% vs. 1.7%, p=0.02). The table below summarizes the changes in treatment by reason for treatment change. Conclusions:For Ph+ CML-CP pts on 2nd-line nilotinib or dasatinib, pts on nilotinib were less likely than those on dasatinibto change treatment due to lack of effectiveness.NilotinibDasatinibP-value(n=301)(n=296)Treatment change due to lack of effectiveness, n (%)6 (2.0)15 (5.1)0.04Discontinuation with or without switch to 3rd-line6 (2.0)14 (4.7)0.06Dose increase0 (0.0)4 (1.4)0.04Treatment change due to intolerance, n (%)11 (3.7)11 (3.7)0.97Discontinuation with or without switch to 3rd-line2 (0.7)3 (1.0)0.64Drug holiday0 (0.0)5 (1.7)0.02Dose decrease9 (3.0)3 (1.0)0.09Treatment change due to other reasons, n (%)18 (6.0)13 (4.4)0.38Discontinuation with or without switch to 3rd-line13 (4.3)6 (2.0)0.11Drug holiday5 (1.7)8 (2.7)0.38 Disclosures:Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Griffin:Novartis: Consultancy, Research Funding.

Characteristics of Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy

AbstractAbstract 4447 Background:Since 2007, nilotinib and dasatinib have been available for 2nd-line therapy for patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. In clinical trials, both drugs have been shown to be effective and safe, but with different side-effect profiles. Currently, little is known about the characteristics of patients who are switched to nilotinib or dasatinib in a real-world setting. Methods:Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to either 2nd-line nilotinib or dasatinib and who had at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients from each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information on patient characteristics at the time of switching TKI therapy was collected, including age, sex, race, comorbidities, prior imatinib dosing, reasons for switching, and the dose regimen of nilotinib or dasatinib at initiation. Characteristics were compared between nilotinib and dasatinib patients using Wilcoxon and chi-square tests. Results:122 hematologists and oncologists provided information on 597 patients (301 on 2nd-line nilotinib and 296 on 2nd-line dasatinib). The table below summarizes the comparisons of the two groups. Both groups had similar age, sex, race, and comorbidity profile. Nilotinib patients were more likely than dasatinib patients to have had secondary imatinib resistance (p=0.047), more likely to have received a maximum imatinib dosing of 600 or 800 mg/day (p=0.006), and less likely to have switched due to imatinib intolerance (p=0.024). Conclusions:Patients switched to nilotinib vs. dasatinib had similar demographic and clinical characteristics at the time of switch, but nilotinib patients were more likely to have had an imatinib dose increase before the switch, and were more likely to have had secondary imatinib resistance. Patients switched to nilotinib vs. dasatinib were also less likely to have had imatinib intolerance. These findings suggest that resistance or intolerance to imatinib therapy have had more impact than patient demographics or clinical characteristics in deciding which drug to use for 2nd-line therapy.Patient characteristicsNilotinibDasatinibP-value(n=301)(n=296)Median age, years (range)60 (22, 83)60 (21, 83)0.431Male n (%)202 (67.1)189 (63.9)0.402Race, n (%)American Indian or Alaska Native7 (2.3)6 (2.0)0.803Asian16 (5.3)24 (8.1)0.172Black or African American42 (14.0)47 (15.9)0.509Hispanic or Latino26 (8.6)15 (5.1)0.085Native Hawaiian or Other Pacific Islander6 (2.0)4 (1.4)0.541White203 (67.4)201 (67.9)0.904Median CML duration, months (range)15 (1,101)13 (1,100)0.110Selected comorbidities, n (%)CML only166 (55.1)159 (53.7)0.725Cardiovascular disease including myocardial infarction, congestive heart failure and peripheral vascular disease42 (14.0)37 (12.5)0.600Dementia4 (1.3)8 (2.7)0.232Chronic pulmonary disease44 (14.6)35 (11.8)0.314Connective tissue disease5 (1.7)10 (3.4)0.180Peptic ulcer disease25 (8.3)30 (10.1)0.440Moderate or severe renal disease7 (2.3)5 (1.7)0.580Cerebrovascular disease with mild or no residual TIA3 (1.0)3 (1.0)0.984Liver disease12 (4.0)17 (5.7)0.318Diabetes36 (12.0)32 (10.8)0.659Other6 (2.0)13 (4.4)0.095Highest imatinib dose, n (%)<400 mg/day154 (51.2)183 (61.8)0.006401-600 mg/day81 (26.9)69 (23.3)601-800 mg/day66 (21.9)44 (14.9)Reason for the switch to a second-line TKI, n (%)Primary imatinib resistance122 (40.5)116 (39.2)0.738Secondary imatinib resistance105 (34.9)81 (27.4)0.047Adverse events or intolerance of imatinib67 (22.3)90 (30.4)0.024Patient not adherent to imatinib3 (1.0)6 (2.0)0.302Other[1]4 (1.3)3 (1.0)0.720[1]Notes: [1] Other reasons for switching from nilotinib included ‘patient's request’ (2), ‘recurrent disease', and ‘data suggest improved efficacy'; from dasatinib, ‘high Sokal score', ‘suboptimal cytogenetic response' and ‘patient compliance'. Disclosures:Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Griffin:Novartis: Consultancy, Research Funding.

Benefits of Early Switching From Imatinib to a Second-Generation Tyrosine Kinase Inhibitor Following 12 Month Complete Cytogenetic Response Failure: A Chart Review Analysis.

AbstractAbstract 2792 Background:The National Comprehensive Cancer Network (NCCN) guidelines (version 1.2013) recommend that patients with chronic myelogenous leukemia in chronic phase (CML-CP) should be tested for cytogenetic response 12 months following imatinib initiation. Failure to achieve complete cytogenetic response (CCyR) at 12 months should result in either an increased dose of imatinib (up to 800mg) or a change to a second-generation tyrosine kinase inhibitor (TKI). This study observed patients who failed to achieve CCyR at 12 months following the initiation of imatinib and compared treatment response rates and disease progression between patients who switched to a second-generation TKI early versus patients who did not. Methods:An online chart abstraction form was used to survey US oncologists and hematologists. Physicians submitted de-identified information on up to 10 adult patients with CML-CP who initiated imatinib as first line therapy (between 01/01/2007 and 26/07/2010) and failed to achieve CCyR at 12 months (between 10–14 months). Patients either switched to a second-generation TKI within 3 months following CCyR failure (early-switchers), or remained on imatinib for ≥3 months following CCyR failure (non-switchers). Non-switchers may have later switched to a second-generation TKI. The index date was defined as the date of the 12-month CCyR failure. Detailed patient information was collected, including demographics, comorbidities, imatinib dosage, and hematologic and cytogenetic response prior to the index date. Cytogenetic response and disease progression was also collected after the index date. CCyR was defined as 0% Philadelphia chromosome positive (Ph+) cells on cytogenetic testing. The proportion of patients achieving CCyR by 6, 12, and 24 months was reported among patients who had ≥1 cytogenetic test during these periods. Documented CCyR was defined as CCyR achievement analyzed among all patients, if patients were not tested for CCyR following the index date they were considered not to have achieved CCyR. Time to first documented CCyR achievement and time to disease progression were both estimated using multivariate Cox proportional hazard ratios (HR), where exposure was calculated from the index date to the first documented CCyR achievement, or to the date of progression, respectively. Multivariate regression analyses controlled for age, sex, race, index year, Charlson comorbidity index, imatinib dose and hematological response prior to index date, percentage of Ph+ cells and CML disease duration at index date, number of days between CML diagnosis and imatinib initiation, and rise in transcript level and chromosome abnormalities in Ph+ cells reported prior to the index date. Results:The majority of the 108 surveyed physicians were from a private practice (72.2%) and a small/intermediate practice size (61.1%). Physicians provided information on 593 patients who failed to achieve CCyR at 12 months; 306 were early-switchers and 287 were non-switchers. Among the non-switchers, 78 later switched to a second-generation TKI, and 104 increased imatinib dose after the index date. Patient demographics and comorbidities were similar among early-switchers and non-switchers, however, results of the 12-month cytogenetic test revealed that early-switchers had a greater number of Ph+ positive cells (51. 5 ± 16.6) compared to non-switchers (47.2 ± 13.1, p=.002). The median follow-up time was 612.5 days (range = 91–1625) and 591 days (range = 365–1623), respectively. Among patients tested for cytogenetic response during the follow-up period (274 early-switchers and 252 non-switchers), 35% of early-switchers subsequently achieved CCyR, compared to 24 % of non-switchers (p=.006). Within 6 months after the index date, 4.7% of the early-switchers achieved CCyR vs. 0.4% of non-switchers; by 12 months, 20.1% vs. 12.3% achieved CCyR; and by 24 months, 33.6% vs. 21.8% achieved CCyR, respectively (all p<.016). After adjusting for confounding factors, early-switchers had an 80% greater documented CCyR achievement rate compared to that of non-switchers (HR=1.80; p=.002) and a progression rate that was 81% lower (3.8% vs.1.5%, HR=0.19, p=.034). Conclusion:Early switching from imatinib to a second-generation TKI following 12-month CCyR failure was associated with better cytogenetic response and a lower risk of progression. Disclosures:DeAngelo:Novartis: Consultancy. Off Label Use: Everolimus in AML. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Styles:Analysis Group, Inc.: Consultancy, Employment, Research Funding. Aberki:Analysis Group, Inc.: Consultancy, Employment, Research Funding. Giguere-Duval:Analysis Group, Inc.: Consultancy, Employment, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Risk of Developing Colorectal Cancer and Benign Neoplasm in Patients with Chronic Constipation

Purpose: To estimate the relative risk of developing colorectal cancer (CRC) and benign neoplasm for patients with chronic constipation (CC) vs. CC-free patients. Methods: Patients ≥18 years with CC (≥2 diagnoses of constipation (ICD-9-CM: 564.0x) between 60 to 365 days apart) were identified from a large retrospective U.S. claims database (Jan1999-Sep2011). Patients with diagnoses of irritable bowel syndrome or diarrhea were excluded. The index date was patient's first eligible diagnosis of constipation. Patients were eligible for the study if they remained enrolled in their health plan for at least 12 months after their index date. The study period for each patient was defined as the time from the patient's index date until the end of his or her available data or diagnosis with CRC or benign neoplasm. Each CC patient was matched 1:3 to CC-free patients by year of birth, sex, and region of residence. CC-free patients were defined as patients who had never been diagnosed for constipation and never had a prescription filled for a laxative during the entire observation period. CRC and benign neoplasm were defined as ≥1 diagnosis for CRC or colorectal benign neoplasm. Prevalence of CRC and benign neoplasm was measured for the one-year period following the index date. In patients free of CRC and benign neoplasm at index date, Poisson regression models were used to determine the relative incidence of developing CRC or benign neoplasm for patients with CC vs. CC-free patients. A sensitivity analysis controlled for the number of colonoscopies, in addition to age, gender, index year, comorbidities and family history of malignancies. Results: On average, CC (N=28,854) and CC-free (N=86,562) patients were 61.9 years old and 33.3% male. The average observation period was 3.99 years (SD=2.45). The one-year prevalence of CRC was 2.7 vs. 1.7% and that of benign neoplasm was 24.8 vs. 11.9% for CC and CC-free patients, respectively. Incidence (per 1,000 patient-years) and incidence rate ratios (IRR) are shown in the result Table.Table: No Caption available.Conclusion: In a large, retrospective, U.S. claims database, patients with CC had significantly greater risk of developing CRC and benign neoplasms over time compared to CC-free patients. Disclosure: Annie Guérin: employee of Analysis Group, Inc, which has received consulting fees from Takeda Pharmaceuticals International, Inc. Reema Mody: employee of Takeda Pharmaceuticals International, Inc. Beverly Fok: employee of Analysis Group, Inc, which has received consulting fees from Takeda Pharmaceuticals International, Inc. Zhou Zhou: employee of Analysis Group, Inc, which has received consulting fees from Takeda Pharmaceuticals International, Inc. Eric Wu: employee of Analysis Group, Inc, which has received consulting fees from Takeda Pharmaceuticals International, Inc. Wen Zhou: employee of Takeda Pharmaceuticals International, Inc. Karen Lasch: employee of Takeda Pharmaceuticals International, Inc. Nicholas J. Talley: Research support from Takeda Pharmaceuticals International, Inc. Katherine Brewer: employee of Takeda Pharmaceuticals International, Inc. This research was supported by an industry grant from Takeda Pharmaceuticals International, Inc.

Comparison of Adherence Between Nilotinib and Dasatinib As Second-Line Therapies in Chronic Myeloid Leukemia

Abstract 2754 Background:According to the NCCN guidelines, the recommended treatment option for patients diagnosed with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) in chronic or accelerated phases who are resistant or develop intolerance to first-line imatinib is to switch to one of the two second-generation BCR-ABL tyrosine kinase inhibitors, nilotinib or dasatinib. There is limited information on their comparative adherence. Analysis of adherence may reveal whether these two drugs are being used as intended and how adherence issues may potentially affect clinical outcomes. Nonadherence to imatinib has been associated with loss of cytogenetic response, imatinib failure, and higher rates of inpatient visits. A prior study covering the period up to 6/2009 has revealed a better adherence profile for nilotinib versus dasatinib. Since dasatinib was approved for once daily use in addition to twice daily use in 05/2009, this study replicated the analysis using more recent data to compare adherence between nilotinib and dasatinib as second-line therapies in CML. Methods:Medical and pharmacy records from two databases from January 1997 to April 2010 were combined to identify adult patients diagnosed with CML (ICD-9 code 205.1x) with ≥1 prescription for either nilotinib or dasatinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date, defined as the first prescription for nilotinib or dasatinib, and to continue their treatment ≥1 month before discontinuing or switching to another TKI. Adherence over an up-to 180-day period was evaluated based on the proportion of days covered (PDC; sum of days of medication on hand for nilotinib or dasatinib divided by the number of calendar days in the study period). Medication possession ratio (MPR) was also evaluated in a sensitivity analysis. PDC and MPR were compared between cohorts using linear regression models. Discontinuation was defined as a treatment gap ≥30 days, and rates were compared between cohorts using Kaplan-Meier survival analyses and Cox proportional hazard regression models. In a sensitivity analysis, discontinuation was defined as a treatment gap ≥90 days. All multivariate regression models were controlled for age, gender, CML complexity, adverse events at baseline, number of inpatient days, emergency room (ER) visits and outpatient visits during baseline, medical costs during baseline, CML year of diagnosis, Charlson Comorbidity Index, and bone marrow or stem cell transplant before the index date. Results:Adherence and discontinuation were analyzed for a total of 558 CML patients receiving a second-line TKI (473 dasatinib and 85 nilotinib). Patient characteristics were generally similar. Patients in the dasatinib cohort had a longer mean follow-up period compared with those in the nilotinib cohort (162 days vs. 146 days; P = 0.0007) and greater utilization and costs associated with inpatient and ER services. The mean PDC over the study period for nilotinib was higher compared with dasatinib (0.81 vs 0.68). After adjusting for confounding factors, the nilotinib group had a 0.115 higher PDC (approximately 17% higher) compared to the dasatinib group (P = 0.0004). Additionally, patients in the nilotinib group had a significantly higher MPR compared to patients in the dasatinib group (0.90 vs. 0.77 P = 0.0043). Discontinuation rates (gap ≥30 days) were significantly higher for dasatinib users than for nilotinib users, with an adjusted hazard ratio of 2.15 (P = 0.0013). Dasatinib-treated patients had higher discontinuation rates than nilotinib-treated patients after 3 months (40% vs 22%) and 6 months (50% vs 28%). These unadjusted differences were robust in the sensitivity analysis with discontinuation defined as a treatment gap ≥90 days, but the difference between the cohorts was no longer significant after adjusting for confounding factors (HR 1.76, P = 0.1328). Conclusions:This retrospective study showed that CML patients treated with nilotinib for second-line treatment were significantly more adherent to therapy, based on PDC and MPR, and had a lower discontinuation rate than did patients receiving dasatinib in this analysis. Further studies are needed to better understand treatment-specific factors affecting adherence and persistence (e.g., treatment cost, tolerability profile, dosing convenience). Disclosures:Guerin:Novartis Pharmaceutical Corporation: Annie Guerin is an employee of Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals. Bollu:Novartis Pharmaceutical Corporation: Employment, Vamsi K. Bollu worked for the Novartis Pharmaceuticals Corporation while performing this analysis but is currently employed by Sunovion Pharmaceuticals Inc. Sunovion Pharmaceuticals Inc. was not in any way associated with this study. Guo:Novartis Pharmaceutical Corporation: Employment. Stepner:Novartis Pharmaceutical Corporation: Michael Stepner is an employee of Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals. Griffin:Novartis Pharmaceutical Corporation: James D. Griffin is an employee of the Dana Farber Institute which has received consultancy fees from Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals Corporation. Wu:Novartis Pharmaceutical Corporation: Eric Q. Wu is an employee of Analysis Group, Inc, which has received consultancy funds from Novartis Pharmaceutical Corporation.