US Healthcare Claims Research Articles

Patterns of Ibrutinib Use, Discontinuation, and Hospitalization Among Patients with Chronic Lymphocytic Leukemia (CLL) in a US Healthcare Claims Database

Introduction:Current treatment options for CLL or small lymphocytic leukemia (SLL) include novel oral therapies that are taken until disease progression. Ibrutinib is approved in frontline and relapsed/refractory CLL and is the most common oral treatment since Food and Drug Administration approval in 2014. Despite favorable responses with ibrutinib, treatment discontinuation occurs (41-50%) (Mato et al. Haematologica 2018; Sharman et al. Blood 2017) and increases the risk of poor overall survival (Follows GA and UK CLL Forum. Poster Presentation 14th International Conference on Malignant Lymphoma Palazzo dei Congressi, Lugano Switzerland, 2017). Previous studies have reported that in addition to disease progression, intolerance and toxicity were primary reasons for discontinuation. However, hospitalizations have not been explored to date. This study used a large US claims database to evaluate ibrutinib treatment patterns and toxicity-related hospitalizations among patients with CLL.Methods:A retrospective analysis of Truven Health MarketScan® Commercial Claims Database was conducted. Patients were included if they initiated ibrutinib treatment (index) between 2/12/2014 and 3/31/2017 and were diagnosed with CLL or CLL along with SLL. Patients were excluded if they had other cancers, did not have at least 180 days of continuous enrollment pre-index (baseline), were treated with ibrutinib within this baseline period, or had less than 180 days of observation after ibrutinib initiation.Patients were categorized into 1 of 3 treatment cohorts: (1) those who had continuous ibrutinib claims without any gap (Users), (2) those who had a treatment gap, but had at least 1 ibrutinib claim after the gap (Retreated), and (3) those who completely discontinued ibrutinib treatment or switched to another treatment (Discontinued/Switched). A gap in treatment was defined as a period of ≥60 days after the end of treatment exposure (Mato et al. Cancer Biology & Therapy 2018). Patient demographics, time to first treatment discontinuation, and frequency of hospital-related adverse events (AEs) were determined for each cohort. AEs were obtained in the 60 days prior to the last ibrutinib claim (pre-discontinuation) and in the exposure period for the last claim plus 60 days after (post-discontinuation). AEs were assessed for the User cohort based on a proxy derived from a median time from initial treatment to discontinuation in the Retreated and Discontinued groups and using the +/- 60-day time window.Results:There were 714 patients included in the analyses. Most patients were male (69%) and the average age at CLL diagnosis was 55.8 years. There were 451 (63%) in the User cohort, 96 (13%) in the Retreated cohort, and 167 (24%) in the Discontinued/Switched cohort.The median time from ibrutinib initiation to end of study observation was 16.8 (6.0-44.2) months. The median time to ibrutinib discontinuation was 4.9 (1.0-40.4) and 6.0 (1.0-34.1) months for the Retreated and Discontinued/Switched cohorts, respectively. For the Retreated cohort, patients were off ibrutinib treatment for a median of 3.2 (2.0-32.0) months before restarting ibrutinib again. Among the Discontinued/Switched cohort, 61% discontinued ibrutinib treatment without receiving any further treatment and 39% switched to another treatment.Retreated and Discontinued/Switched cohorts had higher hospitalization rates compared to the User cohort. The 5 most common inpatient diagnoses were pneumonia, pancytopenia/neutropenia, fever, sepsis, and atrial fibrillation across both the Retreated and Discontinued/Switched cohorts (Table 1). Discontinued/Switched cohort were more likely to have any hemorrhage diagnosis for hospitalization (6%).Conclusion:Consistent with other studies (median follow-up of 17-20 months) (Mato et al. Haematologica 2018; Sharman et al. Blood 2017), the overall treatment discontinuation with ibrutinib in our study was approximately 37% with a median follow-up of 16.8 months. A limitation is that exact reasons for stopping treatment cannot be ascertained from claims data. However, patients who paused or stopped ibrutinib were more likely to have higher rates of hospital-related AEs than those who continued treatment. As treatment discontinuation is likely to occur during a long treatment exposure, oral agents with a finite duration of treatment and with better tolerability are needed for patients with CLL. DisclosuresTo:Genentech, Inc.: Employment, Other: May own stocks/stock options at Roche. Yeh:Genentech, Inc.: Employment, Other: May own stock/stock options at Roche. Biondo:Roche: Equity Ownership; Genentech, Inc.: Employment, Other: May own stocks/stock options at Roche. Masaquel:Genentech, Inc.: Employment, Other: May own stocks/stock options at Roche.

Cost Implications of Anticoagulation Strategies After Percutaneous Coronary Intervention Among Patients With Atrial Fibrillation (A PIONEER-AF PCI Analysis)

The PIONEER AF-PCI trial demonstrated that in atrial fibrillation patients who underwent intracoronary stenting, either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy (Group 1) or 2.5 mg rivaroxaban twice daily plus dual antiplatelet therapy (DAPT) (Group 2) was associated with fewer recurrent hospitalizations, primarily for bleeding and cardiovascular events, compared with standard-of-care vitamin K antagonist and DAPT (Group 3). Associated costs are unknown. This study estimates costs associated with rivaroxaban strategies compared with vitamin K antagonist and DAPT. Medication costs were estimated using wholesale acquisition costs, medication discontinuation rates, and costs of monitoring. Using a large US healthcare claims database, the mean adjusted increase in 1-year cost of care for individuals with atrial fibrillation and percutaneous coronary intervention (PCI) rehospitalized for bleeding, cardiovascular, and other events was compared with those not rehospitalized. Using adjudicated rehospitalization rates from PIONEER AF-PCI, cost differences were estimated. Rates of rehospitalization for bleeding were 6.5%, 5.4%, 10.5%, and 20.3%, 20.3%, 28.4% for cardiovascular events in Groups 1, 2, and 3. Medication and monitoring costs were $3,942, $4,115, and $1,703. One-year costs for all recurrent hospitalization costs and/or patient for the groups were $24,535, $20,205, and $29,756. One-year cost increase associated with bleeding rehospitalizations and/or patient was $4,160, $3,212, and $6,876 and was $13,264, $11,545, and $17,220 for cardiovascular rehospitalizations and/or patient. Overall estimated cost per patient was $28,476, $24,320, and $31,458. Compared with warfarin, both rivaroxaban treatment strategies had higher medication costs, but these were more than accounted for by fewer hospitalizations.

INCREASED INCIDENCE AND PREVALENCE OF PEANUT ALLERGY IN CHILDREN AND ADOLESCENTS IN THE UNITED STATES

Introduction Peanut allergy (PA) is associated with high rates of severe reactions and impaired quality of life, yet epidemiologic data are limited. Utilizing a real-world, nationally representative cohort of children/adolescents, we examined incidence and prevalence of PA. Methods Longitudinal data between January 2011-December 2017 from a geographically and payor-type representative US healthcare claims database were utilized. Patients aged 4-17 years with PA were identified using diagnostic codes and/or services indicating PA-associated severe reactions/anaphylaxis. Prevalence estimates were projected, accounting for dataset capture rates by healthcare setting (40% outpatient clinic, 25% hospital), 30% under-coding, and patient under-presenting (8-15% based on patient age). Estimated annual incidence was defined as PA births as a proportion of all 1-year-old babies. Incidence was computed from prevalence estimates, aging patients back to age 1, adjusting for spontaneous outgrowth of PA (27% by age 12). Results Estimated prevalence of PA was 1.25 million (2.2%) in 2017. Of these patients, ∼500K were diagnosed by allergists; ∼370K diagnosed by pediatricians and managed by allergists; and ∼380K diagnosed and managed by outside of allergists. Common comorbidities included eczema (63%) and asthma (61%); 35% of PA patients had ≥1 additional food allergy. Annual incidence of PA in 1-year-olds increased, from an estimated 1.7% to 5.2% between 2001-2017 (Figure). Conclusions Approximately 2.2% of children/adolescents in the US have PA. Annual incidence has increased since 2001; current annual incidence in 1-year-olds is ∼5%. Findings indicate an increase in both incidence and prevalence of PA, suggesting the impact of PA may be greater than previously reported. Figure. Incidence of PA Among 4–17-Year-Olds in the United States Between 2001–2017

Who diagnosed and prescribed what? Using provider details to inform observational research.

To describe how often patients with depression initiating antidepressants receive their depression diagnosis and prescriptions from the same provider and, when simultaneously initiating benzodiazepines, how often both prescriptions come from the same provider. Using a US healthcare claims database, we created a cohort of adults (18-64years) with a depression diagnosis who initiated antidepressants. We examined concordance by provider specialty and provider identifier between (a) the first antidepressant prescription fill and most proximal depression diagnosis, and (b) the initial antidepressant and benzodiazepine prescription fills among simultaneous benzodiazepine and antidepressant initiators. Among 245166 antidepressant initiators with a recent depression diagnosis (female=67%; median age=39), the specialty of the provider assigning the depression diagnosis matched the antidepressant prescriber's specialty in 94% of cases with known provider details (provider identifier concordance=93%). Concordance was higher for adults diagnosed by a general practitioner (98%) or psychiatrist (92%) than for those diagnosed by a psychologist (74%). In simultaneous new users of antidepressants and benzodiazepines (n=19371), both prescriptions were issued by the same provider specialty and provider identifier 94% and 93% of the time, respectively. The vast majority of patients who received antidepressant prescriptions and depression diagnoses appear to have received both diagnosis and antidepressants from the same provider, suggesting that when antidepressants are issued around the time a patient is diagnosed with depression, the antidepressant was likely prescribed for depression. In addition, the great majority of patients who simultaneously initiate benzodiazepines appear to do so under the direction of one provider.

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.

Decline in Pneumococcal Disease Attenuated in Older Adults and Those With Comorbidities Following Universal Childhood PCV13 Immunization.

BackgroundFollowing introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden.MethodsA retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18–49, 50–64, 65–74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007–2010 (pre-PCV13), 2011–2012 (peri-PCV13), and 2013–2015 (post-PCV13).ResultsAcross study periods, IPD and ACHP rates increased with age (2–27 times higher in persons ≥75 vs 18–49) and comorbidity (4–20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%–48% and ACHP rates declined 4%–19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period.ConclusionsThe switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities.

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.

1085 US Healthcare Claims Analysis of Obstructive Sleep Apnea Comorbidities and Their Association with Stimulant Drug Use

1085 US Healthcare Claims Analysis of Obstructive Sleep Apnea Comorbidities and Their Association with Stimulant Drug Use

Leadless pacemakers: a contemporary review.

Over one million cardiac pacemakers are implanted every year worldwide,[1] of which approximately 200,000 are implanted in the United States alone.[2] Combined with an aging population and increasing pacing indications, these numbers are expected to grow. Since the first pacemaker implantation in 1950s, cardiac pacemaker technology has rapidly advanced. Reduction in generator size, increased battery longevity, quality of pacemaker leads, algorithmic and rate responsive programming―all have revolutionized and transformed the implantation and management of transvenous cardiac pacemaker (TV-PPM). Despite these advances, the potential for complications and technical failure always necessitates consideration. Short-term complications, which have been reported to be as high as 12%,[3] are typically related to the presence of a transvenous lead and or subcutaneous pocket. These complications include pneumothorax, cardiac perforation, lead dislodgement, and pocket infection or hematoma. Long-term complications are also related primarily to the pacing lead and subcutaneous pocket, and include pocket infection, tricuspid regurgitation, venous obstruction, lead fractures and insulation failure. In addition, development of lead related endocarditis is a significant concern, with mortality rates reported between 12%–31%.[4]–[6] Some Studies have shown that long-term complications are primarily related to lead failure, identifying it as the weakest component of the current pacing system.[3],[7] Data obtained from the Truven MarkestScan database, which tracks Medicare and US health care claims, showed a 15%-16% complication rate at three years among 72,701 patients with TV-PPM, representing a significant economic burden to both the patient and healthcare system.[8] Leadless pacemakers were initially conceptualized in the 1970s[9] and successfully implanted in dogs using a mercury battery powered capsule. With advanced battery technology, communication capability, and catheter-based delivery systems leadless pacemakers became a reality. In this paper, we will discuss the current leadless pacing systems focusing on their pros and cons as compared to traditional TV-PPM.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis based on real-world data from 2010 to 2015

Objective: Evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis (PP) continue to receive it in later cycles, and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Available evidence, however, may not be reflective of current clinical practice. We undertook an evaluation to estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received PP in that cycle and all previous cycles versus those who received PP in all previous cycles only, using recent real-world data.Methods: A matched-cohort design and data from two US healthcare claims repositories (2010–2015) were employed. The source population comprised cancer patients who received intermediate/high-risk chemotherapy and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this subset, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (ORs) for FN (broad and narrow definitions) were estimated using generalized estimating equations.Results: Among 47,254 patients in the source population, 9% did not receive second-cycle PP and were matched to those who did. FN odds in cycle 2 were significantly higher among comparison patients versus PP patients (OR [broad definition]: 1.7, p < .001); OR [narrow definition]: 4.3, p < .001). Results for subsequent cycles and for the last cycle, respectively, were comparable (OR [range, broad definition]: 1.6 to 3.1, p < .001 for all; OR [range, narrow definition]: 2.7 to 11.8, p < .001 for all).Conclusions: In this real-world evaluation of cancer chemotherapy patients who received first-cycle PP, FN risk was substantially higher among patients who did not receive PP in subsequent cycles versus those who continued PP.

Risk of exacerbation following pneumonia in adults with heart failure or chronic obstructive pulmonary disease.

BackgroundRecent evidence demonstrates increased short-term risk of cardiac complications and respiratory failure among patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD), respectively, concurrent with an episode of community-acquired pneumonia (CAP). We evaluated patients with pre-existing HF or COPD, beginning 30 days after CAP diagnosis, to determine if CAP had a prolonged impact on their underlying comorbidity.MethodsA retrospective matched-cohort design using US healthcare claims was employed. In each month of accrual, patients with HF or COPD who developed CAP (“CAP patients”) were matched (1:1, without replacement, on demographic and clinical profiles) to patients with HF or COPD who did not develop CAP (“comparison patients”). All patients were aged ≥40 years, and were pneumonia free during prior 1-year period. Exacerbation beginning 30 days after the CAP diagnosis and for the subsequent 1-year period were compared between CAP and comparison patients.Findings38,010 (4·6%) HF patients and 48,703 (5·9%) COPD patients experienced a new CAP episode requiring hospitalization or outpatient care only, and were matched to comparison patients. In the HF subset, CAP patients were 47·2% more likely to experience an exacerbation vs patients without CAP (17·8% vs. 12·1%; p<0·001); in the COPD subset, CAP patients were 42·3% more likely to experience an exacerbation (16·2% vs. 11·4%; p<0·001).ConclusionsOur data provide evidence that CAP foreshadows a prolonged increase in risk of exacerbation of underlying HF or COPD in adults, and suggests a potential benefit to CAP prevention strategies.

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.

Excess Risk of Invasive Pneumococcal Disease (IPD) Persists in Adults with Comorbid Conditions in the Era of PCV13 Childhood and Adult Immunization

BackgroundAdults with comorbid illness are known to be at excess risk of IPD. We evaluated the burden of IPD in adults, with and without comorbidity, during the period before and after introduction of PCV13 in children and selected adults.MethodsWe employed a retrospective cohort design and data from a large US healthcare claims repository. The study population included all adults aged ≥18 years who had ≥1 day of health benefits at any time from 2007–2015, and who met minimum criteria for characterizing comorbidity profiles. Study subjects were stratified by age (18–49, 50–64, and ≥65 years) and risk profile (“at-risk”, “high-risk”, and “healthy”) based on ACIP-identified indications for pneumococcal vaccination. Episodes of IPD were identified in each year of the study period, and rate ratios comparing IPD incidence in persons with at-risk and high-risk conditions, respectively, vs. healthy persons, were computed.ResultsA substantial decline in IPD was observed in 2013–2015 compared with 2007–2010 in healthy, at-risk, and high-risk adults in all age groups. However, the proportional decline was lower in those with high- risk and at-risk conditions, resulting in an increased rate ratio for adults with comorbid conditions (Table).TableIPD rates and rate ratios by age group and risk profileRisk ProfileAge Group (Yr)Annual Rate per 100K, by Time PeriodDecline in Annual Rate from 2007–2010 to 2013– 2015Rate Ratio (95% CI), by Time Period 2007–2010 2013–2015 2007–2010 2013–2015 Healthy 18–49 1.6 0.9 41% -- -- 50–64 3.8 2.6 31% -- -- ≥65 7.0 5.3 25% -- -- At-Risk 18–49 4.5 3.1 31% 2.8 (2.3, 3.6) 3.4 (2.5, 4.4) 50–64 9.9 8.2 17% 2.6 (2.3, 3.0) 3.1 (2.7, 3.7) ≥65 21.4 18.0 16% 3.1 (2.6, 3.5) 3.4 (2.8, 4.2) High- Risk 18–49 16.2 14.2 12% 10.1 (7.9, 12.9) 14.2 (10.9, 18.6) 50–64 27.6 23.5 15% 7.3 (6.3, 8.4) 9.0 (7.6, 10.6) ≥65 36.7 36.4 1% 5.2 (4.5, 6.1) 6.9 (5.7, 8.4) ConclusionIPD burden declined from the pre-PCV13 era. This decline was greatest in healthy adults (vs.. those with at-risk or high-risk conditions); adults with comorbid conditions, especially those ≥65 years old, appear to have benefited least from the direct and indirect impacts of PCV13 immunization. Greater understanding as to which serotypes cause disease in adults with comorbid conditions and which host factors in individuals predispose to IPD is needed to develop additional prevention strategies for high-risk groups.Disclosures S. I. Pelton, Pfizer: Board Member and Grant Investigator, Consulting fee, Research grant and Speaker honorarium; Merck vaccines: Board Member, Consulting fee and Speaker honorarium; GSK: Board Member, Consulting fee and Speaker honorarium; Sequiris: Board Member, Consulting fee and Speaker honorarium; R. Bornheimer, Pfizer, Inc: Consultant, Consulting fee; K. M. Shea, Pfizer, Inc: Consultant and Grant Investigator, Consulting fee and Grant recipient; R. Sato, Pfizer, Inc: Employee and Shareholder, Salary; D. Weycker, Pfizer, Inc: Consultant, Consulting fee

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.