US Healthcare Claims Database Research Articles

Ocular Antihypertensive Medication Use After iStent Implantation Concurrent With Cataract Surgery vs Cataract Surgery Alone in a Large US Health Care Claims Database

The iStent Trabecular Micro-Bypass (Glaukos Corporation) is a minimally invasive glaucoma implant used in conjunction with cataract surgery to lower intraocular pressure. To determine whether implantation of the iStent concurrent with cataract surgery is associated with reduced use of ocular antihypertensive medications in a US health care claims database. Retrospective, observational longitudinal cohort study of individuals enrolled in a US managed care network who underwent iStent implantation with cataract surgery (iStent/CEIOL) from 2012 to 2016 (n = 1509 bilateral and n = 1462 unilateral surgery). A control group of individuals who underwent bilateral cataract surgery only (CEIOL) were matched 1:1 to patients undergoing bilateral iStent/CEIOL on baseline demographic and clinical factors. Data were analyzed between November 1, 2017, and January 31, 2018. The number of topical ocular antihypertensive agents used postoperatively by patients undergoing iStent/CEIOL compared with baseline and with matched CEIOL control individuals, and hazard ratios with 95% confidence intervals for sustained reduced use of at least 1 topical ocular antihypertensive agent postoperatively. Of the 2971 eligible enrollees, mean age at first surgery was 74.3 years, and 1659 (55.8%) were women. Patients undergoing iStent/CEIOL had diagnoses that included primary open-angle glaucoma (n = 2329; 78.4%), narrow angles (n = 381; 12.8%), and secondary glaucomas (n = 261; 8.8%). At baseline, 1223 (41.2%) were receiving no topical glaucoma agents; 876 (29.5%), 437 (14.7%), and 435 (14.6%) were receiving 1, 2, or at least 3 agents, respectively. Although only 678 persons (22.8%) completed at least 2 years of postoperative follow-up, the proportion of patients receiving no drops increased postoperatively (64.7%, 20-24 months, P < .001, χ2). Patients receiving at least 1 topical agent at baseline had mean reduction of 1.01 and 0.61 medications used at 20 to 24 months with bilateral or unilateral surgery, respectively (both P < .001, paired t). Sustained reduction in glaucoma medication use was more likely in patients receiving at least 3 vs 1 medication at baseline (hazard ratio, 1.68; 95% CI, 1.36-2.09). Compared with matched control individuals undergoing CEIOL, patients undergoing bilateral iStent/CEIOL had a greater mean reduction in drops used (0.99 vs 0.49; postoperative month 20-24; P < .001; paired t) and a higher proportion receiving no drops postoperatively (73.5% vs 55.3%, postoperative month 20-24; P < .001; χ2). Implantation of the iStent trabecular micro-bypass stent concurrent with cataract surgery was associated with moderately reduced use of topical ocular antihypertensive medication. Reduction in the use of glaucoma medications may lessen the burden of medication adverse effects and promote better adherence.

Modafinil and the risk of cardiovascular events: Findings from three US claims databases.

This study examined the potential risk of cardiovascular (CV) events associated with modafinil and the consistency of the risk estimates across databases. A retrospective, inception cohort design of patients who initiated treatment with modafinil between 2006 and 2008 was used in three US health care claims databases. Modafinil users were matched with nonusers. Patients were further divided into two cohorts of obstructive sleep apnea (OSA) and non-OSA (NOSA) cohorts. Endpoints of interest, including myocardial infarction (MI), stroke, CV hospitalizations, and all-cause death, were assessed using incidence rates and Cox proportional hazard ratios (HRs), adjusted for potential confounding factors. The cohorts included a total of 175524 patients in MarketScan CM; 77266-in IMS LifeLink; and 8174-in MarketScan Medicaid. No increased risk for MI in the OSA and NOSA cohorts was observed across all three databases. The risks of CV hospitalization in the OSA and NOSA cohorts were not different between the modafinil users and nonusers, except for IMS LifeLink database where the HR was lower than one in the modafinil users compared with the nonusers (HR, 0.69; 95% confidence interval [CI], 0.54 to 0.87). For OSA patients with prior stroke, an adjusted HR of 1.96 (95% CI, 1.02 to 3.76) was observed for stroke among modafinil users compared with nonusers. Among the NOSA, the HRs for all-cause death in the OSA were inconsistent across databases. Except for few CV outcomes, applying one common protocol generated consistent risk estimates of CV events following modafinil use across cohorts and databases.

Healthcare resource use and associated costs of hypoglycemia in patients with type 2 diabetes prescribed sulfonylureas

AimsThe objective of this study was to evaluate diabetes-related healthcare resource use and associated costs in patients with type 2 diabetes (T2DM) treated with a sulfonylurea (SU), with and without hypoglycemia. MethodsIn this retrospective cohort study, patients 18years or older receiving SU monotherapy or as add-on to metformin were identified from a US healthcare claims database (MarketScan®). Of 113,743 patients (56.8% male, average age 62.6years), 61.6% were on SU/metformin dual therapy and 38.4% were on SU monotherapy, and 5% had one or more episodes of hypoglycemia during the 12-month follow-up period. ResultsAdjusted for baseline characteristics, patients with hypoglycemia were three times more likely than those without to use emergency room services (OR 3.04, 95% CI: 2.82, 3.25), almost four times more likely to have inpatient admissions (OR 3.84, 95% CI: 3.58, 4.12), and had more frequent physician office visits (4.3 vs 3.0 visits, p<0.01) in the 12-month follow-up period. The adjusted annual diabetes-related medical expenditure was three times higher in patients with hypoglycemia compared with those without ($6884 vs $2392, p<0.001). ConclusionsThis study demonstrated the higher healthcare utilization and costs associated with hypoglycemia in patients with T2DM treated with an SU.

Cost-effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers as first-line treatment in autosomal dominant polycystic kidney disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disorder impacting ∼1:2,500 individuals among the general US population. Hypertension is a significant predictor of ADPKD progression, and a risk factor for development of cardiovascular disease (CVD), the most common cause for mortality among ADPKD patients. Angiotensin-converting enzymes inhibitors (ACE-I) are widely used as first-line treatment in ADPKD for the management of hypertension. However, their cost-effectiveness relative to other hypertensive medications, such as angiotensin II receptor blockers (ARB), has never been assessed.Objective: To determine if ARB are more cost-effective than ACE-Is as first-line treatment in ADPKD.Methods: A Markov-state decision model was constructed for estimation of cost and outcome benefits in hypertensive ADPKD patients. Transition probabilities were extrapolated from a retrospective cohort study comparing chronic kidney disease (CKD) stage transitions in ADPKD patients. Annual pharmaceutical costs per average daily dose per CKD stage were extracted from a US healthcare claims database. Median total healthcare costs per CKD stage or transplant were extracted from the published literature. The time horizon was set to 30 years, with 1-year duration to cycle shift. A cost-effectiveness analysis was conducted to estimate the incremental cost-effectiveness ratio (ICER) of ACE-I vs ARB per additional year of prevented transplant and/or death. A one-way probabilistic sensitivity analysis was conducted, with 10% variation in probabilities and cost.Results: Total annual healthcare costs accrued after 30 years among ADPKD patients taking ACE-Is was estimated to be $3,505,028.41, compared to ARB at $3,644,327.65. Life expectancy was increased by 1.39 years among patients taking ACE-I. Approximate 10-year survival in patients taking ACE-Is was 47% compared to ARB at 34%.Conclusions: ACE-I dominated ARB and displayed greater cost-effectiveness due to lower cost and increased capacity to prolong years of life without transplant or death among hypertensive ADPKD patients. This model strengthens the value of ACE-I over ARB as first-line treatment for hypertension management in ADPKD patients.

Demographic and clinical characteristics of patients with metastatic colorectal cancer (mCRC) associated with RAS testing from 129 million covered lives.

739 Background: Guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) recommend that all tumors be tested for RAS mutations to identify patients who will most benefit from chemotherapy regimens with biologic agents. The aim of this study was to describe characteristics of patients captured by a large national health claims database who were tested vs those who were not tested for RAS mutations and to identify potential predictors of RAS testing. Methods: Patients with mCRC diagnosed from 2012–2014 (ICD-9 codes 153.x, 154.0x, or 154.1x and 197.x–198.x) were identified from a US healthcare claims database consisting of 129 million unique covered patient lives. Patient demographics and baseline clinical characteristics were compared between patients who were and were not tested for RAS mutations (identified by CPT codes) using chi-square and t-tests. Odds ratios (ORs) were estimated for potential predictors by fitting multivariate logistic regressions to adjust for patient characteristics. Results: Of the 4,527 mCRC patients identified (mean age at diagnosis, 61.2 years; 54% male); 39% (n = 1,787) had a claim for RAS testing during the study period. Patients tested had similar mean age and comorbidity index at diagnosis compared to those not tested (60.8 vs 61.5 years, P = 0.06; 3.98 vs 3.90, P = 0.47). A greater proportion of RAS-tested patients were commercially insured compared to those not tested (37% vs 26%, P &lt; 0.01). Adjusted for other patient characteristics, patients with commercial insurance (OR: 1.62 [95% confidence interval–CI: 1.41–1.87]), metastases to viscera (OR: 1.61 [95% CI: 1.42–1.84]), or diagnosis of colon primary site compared to rectum (OR: 1.32 [95% CI: 1.16–1.51]) had increased odds of receiving RAS testing; all P &lt; 0.01. Conclusions: These observational data show that mCRC patients with commercial insurance, metastases to viscera, and colon cancer have a higher probability of being tested for RAS mutations. Overall, the data suggest that RAS status is underdetermined, with certain subgroups appearing to be more likely to be tested than others.

Economic Burden of Acute Graft-Versus-Host Disease (GvHD) Following Allogeneic Hematopoietic Cell Transplant (HCT) for Hematologic Malignancies

Background: Allogeneic HCT is a potentially curative procedure for many hematologic malignancies, but is associated with several complications. Acute GvHD is a condition that affects 35-50% of allogeneic HCT recipients, typically occurs within 100 days after transplant, and can be life-threatening. Existing treatments are poorly tolerated and frequently ineffective. While the clinical consequences of acute GvHD are understood, the economic burden of the condition has not been well characterized.Methods: Using a large US healthcare claims database (Truven MarketScan® Commercial Claims and Encounters Database), patients aged ≥2 years old were identified who underwent allogeneic HCT between October 2009 and March 2013. Patients without continuous health plan enrollment or evidence of hematologic malignancy in the 6-month period prior to the "Index Admission" (hospital admission during which HCT was performed) were excluded. Patients were followed from the first day of the Index Admission until death, plan disenrollment, or one year; whichever occurred first ("Follow-Up"). Patients were classified into two cohorts: "Acute GvHD" based on ICD-9 CM diagnosis codes within first 100 days of Follow Up, or "No Acute GvHD". Total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) at discharge from Index Admission, the 100th day of Follow-Up, and the 365th day of Follow-Up were determined. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. Total healthcare costs and LOS between the two cohorts were compared for each of the three evaluation periods using Student’s t-tests (unadjusted analyses), and analyses of covariance (ANCOVA; adjusting for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, Charlson Comorbidity Index score, and pre-admission healthcare cost).Results: 1,635 patients underwent HCT and met all selection criteria (mean age was 48 years, 56% were men, acute myeloid leukemia was the most common malignancy); 42% met the criteria for inclusion in the Acute GvHD cohort. Univariate mean total healthcare costs for the Acute GvHD cohort (vs No Acute GvHD) were $36,651 greater during Index Admission, $83,322 greater at the 100th day of Follow-Up, and $123,220 greater at the end of the 1-year Follow-Up (all p<0.01); additional mean LOS (days) were 5.7 during Index Admission, 14.0 at the 100th day of Follow-Up, and 17.4 at the end of the 1-year Follow-Up (all p<0.01) [Table 1]. Multivariate-adjusted mean total healthcare costs were $24,292 greater during Index Admission (p=0.02), $73,622 greater at the 100th day of Follow-Up (p<0.01), and $114,698 greater at the end of the 1-year Follow-Up (p<0.01); additional LOS was 5.2 during the Index Admission, 14.1 at the end of the 100th day of Follow-Up, and 17.9 at the end of the 1-year Follow-Up (all p<0.01) [Table 2].Conclusions: Over the one-year period following allogeneic HCT, patients who develop Acute GvHD experience over $100,000 more in total healthcare costs-and nearly three additional weeks in hospital-relative to those who do not. While healthcare claims appear to represent a good source with which to assess the impact of complications of HCT, confirmation with prospective clinical studies is recommended. Given that nearly one-half of patients develop Acute GvHD, our findings suggest that therapeutic strategies that prevent this complication may confer substantial savings to the healthcare system. [Display omitted] DisclosuresGrubb:Fate Therapeutics: Employment, Equity Ownership. Huse:Evidera: Employment; Fate Therapeutics: Consultancy. Alam:Evidera: Employment; Fate Therapeutics: Consultancy. Dychter:Fate Therapeutics: Employment, Equity Ownership. Wingard:Merck: Consultancy; Ansun: Consultancy; Fate Therapeutics: Consultancy; Gilead: Consultancy; Astellas: Consultancy. Berger:Evidera: Employment; Fate Therapeutics: Consultancy.

Incidence of Gastrointestinal Perforations in Patients with Rheumatoid Arthritis Treated with Tocilizumab from Clinical Trial, Postmarketing, and Real-World Data Sources.

IntroductionThe aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA).MethodsReporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept.ResultsThe clinical trial, global postmarketing, and healthcare claims populations provided 17,906, 382,621, and 3268 patient-years (PYs) of TCZ exposure, respectively. GIP incidence rates [95% confidence interval (CI)] were 1.9 (1.3–2.7), 1.2 (1.1–1.3), and 1.8 (0.7–4.0; specific definition) to 2.8 (1.3–5.2; sensitive definition) per 1000 PYs for the clinical trial, postmarketing, and healthcare claims populations, respectively. The GIP incidence rate (95% CI) for the comparator aTNF healthcare claims population ranged from 0.6 (0.3–1.2) to 0.9 (0.5–1.5) per 1000 PYs, for an absolute rate difference between TCZ and aTNFs of 1.2 (−0.3 to 2.5) to 1.9 (0.0–3.7) per 1000 PYs, corresponding to a number needed to harm between 533 and 828.ConclusionThe TCZ GIP event rates from multiple data sources were consistent with previously reported rates, did not increase over time, and were significantly associated with the number of prior biologics. Comparison of GIP incidence rates among patients with prior biologic exposure suggests that, for every 1000 patients treated with TCZ per year, an additional 1–2 GIP events might occur compared with patients treated with aTNFs.FundingRoche.

Initial Experience With Tofacitinib in Clinical Practice: Treatment Patterns and Costs of Tofacitinib Administered as Monotherapy or in Combination With Conventional Synthetic DMARDs in 2 US Health Care Claims Databases

PurposeTofacitinib is an oral Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis (RA). Tofacitinib can be administered as a monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs). This study describes RA patients’ characteristics, treatment patterns, and costs for those initiating tofacitinib treatment as monotherapy or combination therapy, using US claims data from clinical practice. MethodsA retrospective cohort analysis of patients aged ≥18 years with RA (International Classification of Diseases, Ninth Revision code 714.xx) and with ≥1 tofacitinib claim in the Truven Marketscan (TM) or the Optum Clinformatics (OC) database. Index was defined as the first tofacitinib fill date (November 2012–June 2014). Patients were continuously enrolled for ≥12 months before and after index. Adherence was assessed using the proportion of days covered (PDC) and medication possession ratio (MPR). Persistence was evaluated using a 1.5× days’ supply gap or switch. All-cause and RA-related costs in the 12-month pre- and post-index periods were evaluated. Unadjusted and adjusted analyses were conducted on data on treatment patterns and costs stratified by monotherapy status. FindingsA total of 337 (TM) and 118 (OC) tofacitinib patients met the selection criteria; 52.2% (TM) and 50.8% (OC) received monotherapy and 83.7% (TM) and 76.3% (OC) had pre-index biologic DMARD experience. Twelve-month mean PDC values were 0.56 (TM) and 0.53 (OC), and 12-month mean MPR was 0.84 (TM) and 0.80 (OC), with persistence of 140.0 (TM) and 124.6 (OC) days. Between 12-month pre- and post-index periods, mean (SD) 12-month RA-related medical costs decreased by $5784 ($31,832) in TM and $6103 ($25,897) in OC (both, P < 0.05), whereas total costs increased by $3996 ($30,397) in TM (P < 0.05) and $1390 ($26,603) in OC. There were no significant differences in adherence, persistence, or all-cause/RA-related costs between monotherapy and combination therapy in unadjusted/adjusted analyses. ImplicationsThis analysis adds to the existing tofacitinib knowledge base and will enable informed clinical and policy decision making based on valuable datasets independent of randomized controlled trials.

Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases, 2007 vs 2012: findings from a large US healthcare claims database analysis

Objective To explore trends in demographics, comorbidities, anti-diabetic drug usage, and healthcare utilization costs in patients with newly-diagnosed type 2 diabetes mellitus (T2DM) using a large US claims database.Methods For the years 2007 and 2012, Truven Health Marketscan Research Databases were used to identify adults with newly-diagnosed T2DM and continuous 12-month enrollment with prescription benefits. Variables examined included patient demographics, comorbidities, inpatient utilization patterns, healthcare costs (inpatient and outpatient), drug costs, and diabetes drug claim patterns.Results Despite an increase in the overall database population between 2007–2012, the incidence of newly-diagnosed T2DM decreased from 1.1% (2007) to 0.65% (2012). Hyperlipidemia and hypertension were the most common comorbidities and increased in prevalence from 2007 to 2012. In 2007, 48.3% of newly-diagnosed T2DM patients had no claims for diabetes medications, compared with 36.2% of patients in 2012. The use of a single oral anti-diabetic drug (OAD) was the most common diabetes medication-related claim (46.2% of patients in 2007; 56.7% of patients in 2012). Among OAD monotherapy users, metformin was the most commonly used and increased from 2007 (74.7% of OAD monotherapy users) to 2012 (90.8%). Decreases were observed for sulfonylureas (14.1% to 6.2%) and thiazolidinediones (7.3% to 0.6%). Insulin, predominantly basal insulin, was used by 3.9% of patients in 2007 and 5.3% of patients in 2012. Mean total annual healthcare costs increased from $13,744 in 2007 to $15,175 in 2012, driven largely by outpatient services, although costs in all individual categories of healthcare services (inpatient and outpatient) increased. Conversely, total drug costs per patient were lower in 2012 compared with 2007.Conclusions Despite a drop in the rate of newly-diagnosed T2DM from 2007 to 2012 in the US, increased total medical costs and comorbidities per individual patient suggest that the clinical and economic trends for T2DM are not declining.

Cost Differences of Same-Day Vs Next-Day Use of Pegfilgrastim

Introduction:Febrile neutropenia (FN) is a serious side effect of myelosuppressive chemotherapy that often requires immediate hospitalization. FN is associated with lengthy hospital stays, increased mortality, and high costs. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) such as pegfilgrastim can reduce risk of FN. Per indication, pegfilgrastim should not be administered between 14 days before and 24 hours after cytotoxic chemotherapy. In most clinical trials, G-CSF has been administered the day following chemotherapy, and administration 1-3 days after chemotherapy may result in a lower risk of infection than same-day administration (Burris et al, J Oncol Pract, 2010; Cheng et al, Anticancer Drugs, 2014; Weycker et al, J Clin Oncol, 2015 [abst e17697]). Thus, both NCCN and ASCO recommend pegfilgrastim be given 1-3 days after chemotherapy when possible. A recent retrospective analysis of US health care claims databases showed that same-day pegfilgrastim was used in 13% of cycles (Weycker et al, Blood, 2014). Here we compare the costs of same- vs next-day use of pegfilgrastim (Neulasta®) from a US payer perspective.Methods: We used a published health economic model on the budget impact of G-CSFs to US payers (Taylor et al, Am J Pharm Benefits, 2012) to estimate differences in per-patient costs associated with same- vs next-day pegfilgrastim use among adult patients with early-stage breast cancer (ESBC) or NHL treated with 1 course (6 cycles) of myelosuppressive chemotherapy (TAC for ESBC; R-CHOP for NHL). Data from 2 phase 2 trials (Burris 2010) and 2 large retrospective studies (Weycker 2015; Cheng 2014) identified in a literature search for studies of FN risk with same- vs next-day use of pegfilgrastim in patients with ESBC or NHL were used to derive plausible ranges of estimated cost differences. Ranges were based on variability in the difference of FN risk between groups as reported in or estimated from these studies. The model assumed patients received prophylactic pegfilgrastim and 1 complete blood cell (CBC) count in each chemotherapy cycle. Percentage of FN events requiring hospitalization and costs associated with pegfilgrastim acquisition, administration, lab work, and FN treatment were derived from published literature and public data sources consistent with Taylor 2012. Chemotherapy costs were assumed to be independent of same- vs next-day pegfilgrastim use and were excluded. All costs are presented in 2015 US dollars.Results: Costs for ESBC were $944 to $6,920 greater per patient per course of chemotherapy with same- vs next-day use of pegfilgrastim. Costs for NHL were $629 to $3,775 greater per patient per course of chemotherapy with same- vs next-day use of pegfilgrastim. See table.Conclusions: This analysis suggests that adherence to next-day use of pegfilgrastim is associated with lower costs than same-day use. Cost differences appear to be driven by FN risk and FN treatment, indicating that these results can be reasonably extrapolated to other regimens with an intermediate/high risk of FN.TableEstimates of FN Risk and Per-Patient CostsBreast CancerNHLBurris 2010Weycker 2015Burris 2010Weycker 2015Cheng 2014Same DayNext DaySame DayNext DaySame DayNext DaySame DayNext DaySame DayNext DayFN risk (%)33a11a10b7c17a15a19b14c26d14dPegfilgrastim acquisition$19,815$19,815$19,815$19,815$19,815$19,815$19,815$19,815$19,815$19,815Administration$333$333$333$333$333$333$333$333$333$333CBCs$423$423$423$423$423$423$423$423$423$423FN treatmente$10,380$3,460$3,145$2,202$5,347$4,718$5,976$4,404$8,178$4,404Total cost$30,951$24,031$23,716$22,773$25,918$25,289$26,547$24,974$28,749$24,974Cost differences (next- vs same-day use)(6,920)(944)(629)(1,573)(3,775)Values in parentheses indicate cost savings.a Estimates from Burris 2010; b Estimates from Taylor 2012 for next-day use (7% for TAC and 14% for R-CHOP) were multiplied by relative risk (TAC: 1.36; R-CHOP: 1.33), which was calculated from the cycle-level odds ratio (1.4) reported in Weycker 2015; c Estimates from Taylor 2012; d Estimates from Taylor 2012 for next-day use (14% for R-CHOP) were multiplied by relative risk (1.84), which was calculated from cycle-level results in Cheng 2014 (9.4% for same-day use and 5.1% for next-day use); e Based on current literature, we assumed that the likelihood that an FN event would require hospitalization was 80%. DisclosuresLi:Amgen, Inc.: Employment, Equity Ownership. Off Label Use: This abstract describes costs associated with same-day administration of pegfilgrastim, which is an off label use of pegfilgrastim. As noted in the abstract text, "Per indication, pegfilgrastim should not be administered between 14 days before and 24 hours after cytotoxic chemotherapy.". Zhang:Amgen Inc.: Other: Internship. Lin:Amgen Inc.: Employment, Other: stock ownership. Fust:Optum: Employment; Amgen Inc.: Consultancy, Research Funding. Garcia:Amgen Inc: Employment, Equity Ownership.

Predictors of Second-Line Treatment Choice with Triplet Therapy in Routine Care Among Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

BackgroundBeginning with the IFM 2005-04/MMVAR trial, three-drug combinations (TCs) have demonstrated superior clinical outcomes compared with two-drug regimens among patients with RRMM (Garderet JCO 2012). TCs are emerging as the standard of care at first relapse. We assessed factors that influenced treatment choice with TCs in a cohort of patients with RRMM who were managed in routine care.MethodsWe identified adult patients with MM between January 2008 and February 2014 in a large, national, US healthcare claims database of commercially insured and Medicare Advantage beneficiaries. Newly diagnosed patients were followed from the first claim with an ICD-9 code for MM (with a 12-month wash-out period). To ensure completeness of claim history, patients with continuous enrollment from 12 months pre-diagnosis through at least initiation of second-line therapy (SLT) for RRMM were included. Those with claims for transplants were excluded. Front-line therapy (FLT) began with the first claim for MM-directed systemic cancer therapy. Unique agents administered within 90 days of FLT initiation constituted a regimen. Continuation of FLT regimen (or part thereof) or monotherapy within 3 months of the end of the initial regimen was considered part of FLT. SLT after first relapse for RRMM was identified accordingly: 1) a treatment gap >6 months between end of FLT and start of a second regimen (retreatment or switch), 2) start of a follow-up regimen (retreatment) with a treatment gap of >3 and up to 6 months after end of FLT, or 3) a switch to another drug combination after FLT regimen. The first claim for SLT was the index date. SLT ended at the earliest of: start of a new drug, death, or end of study period (February 2014). Patients were grouped into those receiving one-/two-(1-2) vs three-/four-drug (3+) combinations based on the number of unique cancer therapy agents received within the start and end date of SLT. A logistic multivariable model was used to identify factors independently associated with receipt of 1-2 vs 3+ SLT regimens.ResultsBaseline characteristics among 249 RRMM patients on SLT are shown in Table 1 according to receipt of 1-2 vs 3+ SLT regimens. Among 62 patients who initiated SLT in 2013-14, 14 (23%) received a 3+ SLT regimen (vs 19 (10%) prior to 2013). Adjusting for gender and CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone disease), predictors of 3+ SLT included: younger age (<65 years), early relapse (time to next therapy [TTNT], interval from start of FLT to start of SLT, <6 months), 3+ agents in FLT and index year of SLT initiation (in 2013-14). Charlson Comorbidity Index (CCI) was not independently associated with receipt of 3+ SLT.ConclusionsA majority of patients do not receive triplet-based SLT in routine care. Younger age, and not comorbidity status, appears to be the discriminatory patient characteristic for triplet therapy choice. Introduction of triplets with a favorable toxicity profile and assessment for comorbidity status in routine practice represent steps towards optimizing treatment choices in RRMM.Table 1Baseline Characteristics among Patients with RRMM According to SLT Type (N=249)N (%)Monotherapy/Doublet (1-2) (N=216)Triplet/Quadruplet (3+) (N=33)Total (N=249)TTNT<6 months44 (20.4%)14 (42.4%)58 (23.3%)≥6 months172 (79.6%)19 (57.6%)191 (76.7%)Age, years<6553 (24.5%)17 (51.5%)70 (28.1%)65-7464 (29.6%)8 (24.2%)72 (28.9%)≥7599 (45.8%)8 (24.2%)107 (43%)Male105 (48.6%)16 (48.5%)121 (48.6%)CCI060 (27.8%)10 (30.3%)70 (28.1%)152 (24.1%)3 (9.1%)55 (22.1%)2+104 (48.1%)20 (60.6%)124 (49.8%)CRAB symptoms147 (68.1%)26 (78.8%)173 (69.5%)Number of agents in FLT regimen1-2147 (68.1%)12 (36.4%)159 (63.9%)3+69 (31.9%)21 (63.6%)90 (36.1%)Table 2Predictors of 3+ SLT in RRMM (N=249)Odds Ratio (OR) for 3+ vs 1-2 SLT(95% CI for OR)Age, years<65 65-74 ≥753.10 1.36 Reference(1.13 - 8.51)* (0.45 - 4.09) -Male1.13(0.51 - 2.51)Index year2008-2012 ≥2013Reference 3.42- (1.42 - 8.21)**TTNT, months≥6 <6Reference 2.54- (1.05 - 6.17)*CRAB symptoms at baseline1.69(0.63 - 4.58)CCI0 1 2+Reference 0.41 0.98- (0.10 - 1.62) (0.39 - 2.46)Number of agents in FLT regimen1-2 3+Reference 2.77- (1.20 - 6.42)**significant at 5%; **significant at 1% DisclosuresRomanus:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Jhaveri:Takeda Pharmaceutical Company Limited: Equity Ownership; Sanofi: Equity Ownership; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Labotka:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Henk:Optum (a consulting firm retained by Takeda to conduct the reasearch pertaining to this abstract): Employment. Seal:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment.

Economic Burden of Infections Following Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies

Background: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option for many hematologic malignancies, but is associated with numerous complications, including infection. While the clinical consequences of infection post-HCT have been well characterized, details of their economic burden have not.Methods: Using a large US healthcare claims database, we identified patients aged ≥2 years who underwent allogeneic HCT between October 2009 and March 2013. The hospital admission during which HCT was performed was deemed the "Index Admission". We excluded patients without continuous health plan enrollment and evidence of a hematologic malignancy in the 6-month period prior to the Index Admission. Patients were followed from discharge of the Index Admission until death, plan disenrollment, or one year, whichever occurred first ("Follow-Up"). We ascertained the incidence of infections during the Index Admission through 100 days after discharge ("Early Infections"), and examined by etiology (bacterial, viral, fungal, other/unknown) using relevant ICD-9-CM diagnosis codes. We then ascertained total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) during the Index Admission and Follow-Up. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. We compared total healthcare costs and LOS during the Index Admission, Follow-Up, and Overall (Index Admission + Follow-Up) between patients who did versus did not experience an Early Infection using Student's t-tests (unadjusted analyses), and analyses of covariance (ANCOVA) to adjust for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, and comorbidities.Results: A total of 1,635 patients were identified who underwent allogeneic HCT and met all selection criteria; mean age was 48.4 years, 55.6% were men, and acute myeloid leukemia was the most common malignancy (41.8%). A total of 77.7% of patients (n=1,270) experienced ≥1 Early Infections: bacterial (45.5%), viral (33.2%), fungal (19.5%), and other/unknown (54.1%). Univariate findings are presented in the table. Compared to patients without Early Infections, multivariate-adjusted mean total healthcare costs among patients with Early Infection were $69,044 greater during Index Admission, $74,307 greater during Follow-Up, and $143,351 greater Overall; corresponding increases in LOS were 8 days, 10 days, and 18 days, respectively (all p<.001).Conclusions: Nearly four-in-five patients who undergo allogeneic HCT experience Early Infections. These infections are associated with significant increases in healthcare costs and hospital LOS. Our findings suggest new therapies capable of preventing infection - especially across etiologies- could be impactful from an economic perspective.Table 1Mean (SD) Total LOS and Healthcare Costs, by Time Since Allogeneic HCT and Early Infection StatusType of InfectionOverallIndex AdmissionFollow-Up PeriodWITHInfectionWITHOUT Infectionp-valueWITHInfectionWITHOUT Infectionp-valueWITHInfectionWITHOUT Infectionp-valueTotal LOS, daysAny Infection56.9 (41.8)38.0 (25.2)<.00135.2 (22.7)26.7 (14.6)<.00121.7 (34.5)11.3 (22.0)<.001Bacterial63.9 (46.4)43.4 (29.6)<.00137.4 (23.9)29.9 (18.5)<.00126.4 (38.6)13.5 (24.7)<.001Viral64.5 (48.8)46.8 (32.4)<.00137.7 (24.3)31.1 (19.6)<.00126.8 (40.3)15.7 (27.0)<.001Fungal68.1 (52.0)49.0 (34.9)<.00140.4 (27.2)31.6 (19.4)<.00127.7 (41.7)17.4 (29.4)<.001Other/ Unknown59.3 (43.5)45.0 (32.6)<.00136.4 (23.9)29.7 (17.4)<.00122.8 (35.6)15.3 (27.7)<.001Total Healthcare Costs, $Any Infection479,162 (387,142)310,911 (203,337)<.001262,290 (231,969)178,560 (105,550)<.001216,871 (294,604)132,350 (171,085)<.001Bacterial517,802 (413,054)377,972 (297,137)<.001275,178 (238,242)217,228 (186,010)<.001242,624 (317,973)160,743 (224,804)<.001Viral561,509 (460,937)381,977 (281,459)<.001296,565 (268,145)217,260 (174,118)<.001264,944 (350,792)164,716 (219,322)<.001Fungal552,653 (464,501)414,682 (326,023)<.001293,649 (263,916)231,466 (197,292)<.001259,003 (354,145)183,216 (248,892)<.001Other/ Unknown495,675 (396,898)377,794 (302,142)<.001270,943 (236,232)211,331 (177,328)<.001224,731 (307,157)166,462 (225,358)<.001 DisclosuresBerger:Evidera: Employment; Fate Therapeutics, Inc: Research Funding. Grubb:Fate Therapeutics, Inc: Employment, Equity Ownership. Huse:Fate Therapeutics, Inc: Research Funding; Evidera: Employment. Mohanty:Evidera: Employment; Fate Therapeutics, Inc: Research Funding. Ferraro:Fate Therapeutics, Inc: Employment, Equity Ownership. Daniels:Fate Therapeutics, Inc: Employment, Equity Ownership. Levin:Fate Therapeutics, Inc: Employment, Equity Ownership.

Hepatic outcomes among adults taking duloxetine: a retrospective cohort study in a US health care claims database.

BackgroundHepatic injury has been reported following duloxetine use. This study further examines the hepatic safety of duloxetine in a large US health insurance database.MethodsIn this propensity score-matched cohort analysis in a US commercially insured population (01 August 2004 to 31 December 2010), we compared individuals with depression and without liver disease who initiated duloxetine to comparators (venlafaxine or selective serotonin reuptake inhibitors [SSRIs], and individuals with pharmacologically untreated depression). We estimated incidence rates (IR) and 95 % confidence intervals (CI) for medical record-confirmed hepatic-related death, liver failure, and other clinically significant hepatic injury.ResultsAmong 30,844 duloxetine initiators, 21,000 were matched to venlafaxine initiators, 28,479 to SSRI initiators, and 22,714 to untreated patients. There were no cases of hepatic-related death or liver failure. IRs of other clinically significant hepatic injury without documented alternate etiologies were higher but not statistically significant among duloxetine initiators compared to initiators of venlafaxine (0.7/1000 person-years [PY] [95 % CI: 0.2 − 1.5] vs. 0.0/1000 PY [95 % CI: 0.0 − 0.3]) and SSRIs (0.4/1000 PY [95 % CI: 0.1 − 1.0] vs. 0.0/1000 PY [95 % CI: 0.0 − 0.3]). IRs were similar among duloxetine and untreated patients (0.5/1000 PY [95 % CI: 0.1 − 1.3] vs. 0.5/1000 PY [95 % CI: 0.1 − 1.5]). When hepatic outcomes were considered irrespective of alternate etiologies, similar results were observed.ConclusionsOur findings, while not statistically significant, may suggest a higher incidence of hepatic injury other than hepatic-related death or liver failure among duloxetine initiators compared to venlafaxine and possibly SSRIs, but not untreated patients. These differences remain consistent with chance, and an elevated risk cannot be ruled in or out.

Impact of initiation of asenapine on patterns of utilization and cost of healthcare resources associated with the treatment of bipolar I disorder

Objective:To assess the impact of initiation of asenapine on “real-world” levels of utilization and cost of healthcare services for the treatment of bipolar I disorder (BPD) in the US.Methods:Using two large US healthcare claims databases that collectively included commercially insured patients aged < 65 years and Medicare enrollees, this study identified all adults (≥18 years) with evidence of BPD who began therapy with asenapine between 2009–2012. The date of the earliest claim for asenapine during this period was deemed the ‘index date’, and patients without continuous enrollment for the 6-month periods before and after this date were excluded (‘pre-index’ and ‘post-index’, respectively). Healthcare claims with a BPD diagnosis, plus psychiatric medications and the costs thereof (2012 dollars) were deemed ‘BPD-related’. Differences in BPD-related utilization and cost of healthcare services were compared between the pre- and post-index periods.Results:A total of 1403 patients met all selection criteria; the mean age was 42.8 years and 70.6% were women. Relative to pre-index, significant decreases were noted in post-index use of BPD-related healthcare services, most notably admissions (from 24.0% to 12.3% during the post-index period) and emergency department visits (from 4.6% to 2.6%) (both p < 0.05). While pharmacy costs increased, mean total post-index BPD-related healthcare costs were $979 lower than pre-index ($5002 vs $5981; p < 0.05), primarily due to the decrease in BPD-related admissions.Conclusions:Relative to the 6-month period beforehand, levels of utilization of BPD-related healthcare services and costs decreased during the 6-month period immediately following initiation of asenapine therapy.

First-, Second- and Third-Line Lung Cancer Treatment Patterns And Associated Costs in a US Healthcare Claims Database

Aim: To identify the most common first, second, and third lines of therapy and associated costs among patients treated for lung cancer. Methods: This retrospective analysis of healthcare claims identified patients treated for lung cancer from January 2007 through April 2012. Patients were enrolled in first-, second-, or third-line therapy cohorts and stratified by the number of discrete treatments received or by the specific chemotherapy or biologically targeted agent or combination of agents. Results: Of patients receiving first-line treatment (either chemotherapy or biologically targeted therapies), 18.3% and 4.4% received second-line and third-line treatment, respectively. Pemetrexed, topotecan, docetaxel, and erlotinib were the most commonly second-line regimens; pemetrexed and erlotinib were the most common third-line regimens. While total costs increased with increasing lines of treatment, costs per patient per month remained stable or decreased overall. Conclusion: Platinum/taxane combined treatment is still the mainstay of first-line therapy for lung cancer treatment for those with advanced disease. Second- and third-line therapy is still prescribed infrequently, although newer agents are more commonly used in this setting.

Abstract P6-10-01: Risk of chemotherapy-induced febrile neutropenia (FN) in patients (pts) with non-metastatic breast cancer (BC) and documented risk factors for FN

Abstract Background: Clinical practice guidelines recommend primary prophylactic colony-stimulating factor (CSF) for pts with cancer receiving myelosuppressive chemotherapy when their risk of FN is high (≥20%). Evaluating FN risk in pts who receive regimens that are not documented as high risk in guidelines can be challenging; these pts may be at a high risk of developing FN based on a combination of regimen and pt risk factors. This retrospective study estimated FN risk among subgroups of pts with non-metastatic BC receiving 1 of 3 commonly used, non-high risk chemotherapy regimens. Methods: Pt-level data from 2 US healthcare claims databases comprising medical and outpatient pharmacy claims from commercial and Medicare supplemental plans were pooled. Eligible pts were ≥18 years old and had initiated a course of TC, TCH, or non-dose-dense AC/AC-T for non-metastatic BC between July 1, 2003 and June 30, 2012. Occurrence of FN during any cycle of the first chemotherapy course was identified using diagnosis codes for neutropenia, fever, or infection. Risk factors, documented in guidelines and the published literature, were evaluated during the 12 months before chemotherapy initiation. The percentage of pts, FN risk, and relative risk (RR, compared to pts with no risk factors) for subgroups of pts with specific risk factors are presented. Results: 50,893 pts were included in the analysis. FN risks by chemotherapy regimen and subgroup are shown in the table. TC N=26,266TCH N=9,105AC/AC-T N=15,522 % PtsFN Risk (RR, 95% CI)% PtsFN Risk (RR, 95% CI)% PtsFN Risk (RR, 95% CI)Any risk factor78.114.2 (1.4, 1.3-1.5)74.516.9 (1.3, 1.2-1.5)73.616.6 (1.6, 1.4-1.7)Age ≥6515.116.3 (1.6, 1.4-1.7)11.516.3 (1.3, 1.1-1.5)11.417.9 (1.7, 1.5-1.9)Chronic comorbidities Cardiovascular disease16.816.9 (1.6, 1.5-1.8)14.620.2 (1.6, 1.4-1.8)16.619.5 (1.8, 1.6-2.1)Diabetes11.817.4 (1.7, 1.5-1.9)10.221.3 (1.7, 1.4-2.0)11.120.4 (1.9, 1.7-2.2)Liver disease1.918.7 (1.8, 1.5-2.2)2.220.8 (1.6, 1.2-2.2)2.017.8 (1.7, 1.3-2.2)Lung disease2.023.4 (2.3, 1.9-2.7)1.530.7 (2.4, 1.8-3.2)1.927.1 (2.6, 2.1-3.2)Renal disease1.322.7 (2.2, 1.8-2.7)0.925.0 (2.0, 1.3-2.9)1.026.8 (2.5, 1.9-3.3)Osteoarthritis7.019.6 (1.9, 1.7-2.1)6.121.1 (1.7, 1.4-2.0)6.020.8 (2.0, 1.7-2.3)Thyroid disorder13.015.4 (1.5, 1.3-1.7)11.917.4 (1.4, 1.2-1.6)10.617.2 (1.6, 1.4-1.9)Number of risk factors 133.211.7 (1.1, 1.0-1.2)33.914.1 (1.1, 1.0-1.3)33.714.2 (1.3, 1.2-1.5)224.613.8 (1.3, 1.2-1.5)23.217.4 (1.4, 1.2-1.6)22.916.0 (1.5, 1.3-1.7)312.516.3 (1.6, 1.4-1.8)11.219.8 (1.6, 1.3-1.8)11.121.3 (2.0, 1.8-2.3)4+7.822.8 (2.2, 2.0-2.5)6.125.0 (2.0, 1.6-2.3)5.924.8 (2.3, 2.0-2.7)Reference group (0 risk factor)21.910.4 (NA)25.512.7 (NA)26.411.6 (NA)Selected risk factors are presented. A high proportion of pts (74%-78%) had ≥1 risk factor for FN, and these pts had a higher FN risk than pts with no risk factors. 55.4%, 56.7%, and 42.2% of all pts who received TC, TCH, or AC/AC-T, respectively, received CSF prophylaxis in cycle 1. Conclusions: FN risk assessments are needed for pts who are receiving non-high risk regimens. Citation Format: Derek Weycker, Xiaoyan Li, Richard Barron, Hongsheng Wu, Phuong Khanh Morrow, Hairong Xu, Maureen Reiner, Jacob Garcia, Shivani Mhatre, Gary Lyman. Risk of chemotherapy-induced febrile neutropenia (FN) in patients (pts) with non-metastatic breast cancer (BC) and documented risk factors for FN [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-01.

Use of Chemotherapy and Same-Day Pegfilgrastim Prophylaxis in US Clinical Practice

Background: Primary prophylaxis with pegfilgrastim has been shown to reduce the risk of febrile neutropenia, a life-threatening consequence of myelosuppressive chemotherapy. Pegfilgrastim is not indicated for administration during the interval between 14 days before and 24 hours after cytotoxic chemotherapy because pegfilgrastim induces proliferation of myeloid progenitor cells, and these proliferating cells may be especially sensitive to myelotoxic agents. A randomized, double-blind, phase 2 study (Burris 2010) and observational studies (Skarlos 2009, Cheng 2014) have reported poorer outcomes with same-day pegfilgrastim administration compared to next-day administration. Nonetheless, some healthcare providers administer pegfilgrastim to their patients on the same day as chemotherapy rather than requiring the patients to return for an injection the next day. This is the first large-scale analysis of same-day pegfilgrastim use in US clinical practice.Methods: In this retrospective cohort study, we examined the day of administration of pegfilgrastim prophylaxis relative to the completion of chemotherapy in adults with solid tumors (eg, breast cancer, colorectal cancer, and lung cancer) and non-Hodgkin’s lymphoma (NHL) treated in the outpatient setting. Data spanning 2003–2011 were obtained from 2 large private US healthcare claims databases—the Truven Health Analytics MarketScan® Database and the IMS Health PharMetrics Plus™ Database—and were pooled for analysis. Only patients who received triweekly (Q3W) or monthly (Q4W) chemotherapy regimens were included. For each patient, only the first documented chemotherapy course was included, and in the first course, only cycles with medical claims for pegfilgrastim prophylaxis were included. Administration of pegfilgrastim prophylaxis was classified as day 0 (same day), day 1, days 2-3, or days 4-5 relative to the last day of administration of myelosuppressive chemotherapy in the cycle. Analyses were conducted on an overall basis as well as by tumor type and chemotherapy regimen.Results: We identified 69,509 patients who received pegfilgrastim prophylaxis in 244,687 chemotherapy cycles. We found that pegfilgrastim was administered on the same day as chemotherapy in 13.4% of first cycles and 13.0% of subsequent cycles. Table 1 shows patient characteristics for 4 of the most common tumor types. Table 2 shows the day of pegfilgrastim administration.Conclusion: This large retrospective study provides data on the prevalence of same-day pegfilgrastim administration in US clinical practice. Despite dosing guidance on the pegfilgrastim label and prior research, an important minority of patients are receiving same-day prophylaxis. A future study will evaluate clinical outcomes in this study population.Table 1Breast CancerColorectal CancerLung CancerNHLNo. of patients33,0761,25112,88810,433Age, mean (SD), years54.8 (10.3)60.1 (11.3)64.6 (9.9)62.9 (13.7)Age < 65, %84.768.553.356.5Age ≥ 65, %15.331.546.743.5Male, %0.042.954.254.2Most common regimen, (%)AC/AC-T (27.4)FOLFOX (42.4)Carboplatin + paclitaxel (22.8)CHOP-R (62.1)Abstract 4825. Table 2Cycle 1Cycles 2+Day of Administration of Pegfilgrastim Prophylaxis*, %Day of Administration of Pegfilgrastim Prophylaxis*, %No. of CyclesSame DayDay 1Days 2-3Days 4-5No. of CyclesSame DayDay 1Days 2-3Days 4-5All cancer49,02813.468.516.31.8195,65913.069.815.71.5Breast cancer24,07412.574.112.60.998,95512.175.411.61.0AC/AC-T5,26016.170.112.90.827,56313.972.912.11.1Colorectal cancer56319.722.443.214.73,9208.119.166.96.0FOLFOX16311.016.069.93.12,1275.317.174.03.7Lung cancer9,18411.762.424.51.429,43411.961.325.51.4Carboplatin + paclitaxel2,22311.172.715.11.15,97712.074.113.10.9NHL7,81413.070.415.61.030,06712.473.113.51.0CHOP-R4,89112.273.014.00.820,90511.775.711.90.8*Relative to last day of administration of myelosuppressive chemotherapy DisclosuresWeycker:Amgen Inc.: Research Funding. Wu:Amgen Inc.: Research Funding. Hagiwara:Amgen Inc.: Research Funding. Li:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership.

Treatment patterns and costs in second-line (2L) metastatic colorectal cancer (mCRC).

544 Background: Administrative claims databases are an important data source to examine treatment (tx) patterns, costs and outcomes, but are subject to limitations. This study included a chart review to assess a claims-based algorithm for identifying 2L mCRC patients (pts). Tx patterns and costs were compared between mCRC pts treated with bevacizumab (BEV) or cetuximab (CET). Methods: 2LmCRC pts were identified from a US commercial insurance claims database (1/2008-6/2011). Initial identification required pts to have ≥2 claims ≥30 d apart for colon or rectal cancer and metastatic (met) disease. Continuous enrollment for ≥6 mo before and after the date of 1st met claim, ≥2 lines of therapy (LOT), and 2L tx with BEV or anti-EGFR was required. 2L was defined as addition of any new agent ≥28 d after start of 1st LOT. Charts from 92 pts were abstracted and used to refine and corroborate the algorithm. Generalized Linear Models (GLM) were used to assess differences in healthcare costs between patients on BEV or CET during 2L. Results: The match rate of claims identified mCRC pts treated with multiple lines of therapy confirmed by chart abstraction ranged from 85% to 97%. Applying the final algorithm to the overall claims data resulted in the identification of 569 pts: 450 pts receiving BEV and 119 pts receiving CET. A total of 38 panitumumab patients were excluded from analysis due to small sample size. Pt characteristics were similar; mean age was 61 years and 58% were males. In 2L, BEV was commonly used with 5FU or capecitabine-based regimens (81%) and CET with irinotecan-based regimens (73%). BEV pts had significantly lower all-cause healthcare costs (adjusted difference: –$12,239, p=0.02), and medical costs (–$13,672, p=0.01) during 2L. While on second-line therapy, BEV pts also had lower average monthly all-cause and medical costs than CET pts. Sensitivity analysis using variations of the case finding algorithm yield similar results. Conclusions: The use of BEV during second line treatment of mCRC was found to be associated with significantly lower healthcare costs relative to the use of CET from a large US healthcare claims database.

Post-Marketing Assessment of Neuropsychiatric Adverse Events in Influenza Patients Treated with Oseltamivir: An Updated Review

A 2008 review by our group concluded that the risk of neuropsychiatric adverse events (NPAEs) in influenza patients was not increased by oseltamivir exposure, and did not identify any mechanism by which oseltamivir or its metabolites could cause or worsen such events. The current article reviews new information on this topic. Between September 16, 2007 and May 15, 2010, 1,805 spontaneously-reported NPAEs were identified in 1,330 patients receiving oseltamivir: 767 (42.5%) from Japan, 296 (16.4%) from the USA, and 742 (41.1%) from other countries. NPAEs were more common in children: 1,072 (59.4%) events were in those aged ≤16 years. NPAEs often occurred within 48 h of treatment initiation (953 events; 52.8%). Nearly half of the events were serious in nature (838; 46.4%). The three largest categories of events were abnormal behavior (457 events, 25.3%), miscellaneous psychiatric events (370; 20.5%), and delusions/perceptual disturbances (316 events, 17.5%). A total of 1,545 events (85.6%) in eight different categories were considered to be delirium or delirium-like. Twenty-eight suicide-related events were reported. A US healthcare claims database analysis showed that the risk of NPAEs in 7,798 oseltamivir-treated patients was no higher than that in 10,411 patients not on antivirals, but a study on oseltamivir and abnormal behavior in Japan was less conclusive. NPAE frequency in oseltamivir-exposed Japanese and Taiwanese children with influenza was the same as in unexposed children. New analysis of the UK General Practice Research Database showed that the relative adjusted risk of NPAEs in influenza patients was 2.18-times higher than in the general population. Other epidemiology studies report frequent occurrence of encephalitis and similar disorders in influenza patients independently of oseltamivir exposure. The new data support the findings of the original assessment. Evidence suggests that influenza-related encephalopathies are caused by influenza-induced inflammatory responses, but more work is needed to confirm the underlying mechanisms.

Economic burden of adverse events in patients with metastatic renal cell carcinoma (mRCC).

e16573 Background: To estimate costs associated with adverse events (AEs) in patients receiving targeted therapies indicated for first-line treatment of mRCC. Methods: A retrospective study using a large US healthcare claims database (PharMetrics) from 1/2000 to 12/2009 was conducted. Study subjects were aged ≥18 years, had mRCC, and received first-line treatment with targeted therapies. AEs of interest comprised abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, and proteinuria. Patients receiving care for these AEs were identified using ICD-9-CM diagnosis/procedure codes on healthcare claims. Costs were examined over a 30-day period, beginning with date of first mention of each AE; non-evented patients were assigned a “shadow” index date for comparison purposes. We estimated total costs over 30 days following the index date for patients with and without AEs, on both unadjusted basis and following adjustment for differences in baseline characteristics using a generalized linear model (GLM). Direct costs of targeted therapy were not considered. Results: Among patients receiving targeted therapy for mRCC, 64% had healthcare encounters for one or more AEs. AEs occurring with frequency &gt;20% included severe abdominal pain, back pain, fatigue/asthenia, and nausea/vomiting, respectively; 10-20% of patients had encounters for diarrhea, dyspnea, and extremity pain, respectively. Mean [SD] total costs of care during the 30-day, post-index period were substantially higher among patients with AEs ($12,177 [$19,621] vs $4070 [$8142] for those without AEs). Adjusting for differences in baseline characteristics, the estimated cost difference (95% CI) was $11,373 ($5286 - $21,419). Conclusions: Costs associated with AEs of first-line targeted therapies are substantial in patients with mRCC. Efforts to prevent and/or better manage these events may reduce healthcare costs.