Incidence and risk of hypertension in patients newly treated for multiple myeloma: a retrospective cohort study.

BACKGROUND: Hypertension is commonly reported in multiple myeloma (MM) patients and may be associated with older age, disease-related complications and consequences of MM treatments. This study evaluated the incidence rates of and risk factors for hypertension and malignant hypertension in newly-treated MM patients in the United States. METHODS: Newly-treated adult MM patients were identified from Truven MarketScan claims database from 1/1/05 to 3/31/14. Inclusion criteria were new diagnosis of MM with start of MM treatment, ≥12 months continuous enrollment prior to diagnosis, ≥30 days of continuous enrollment following initial diagnosis, and prescription drug coverage. Non-MM patients were matched for age (within +/- 5 years), sex and distribution of index dates to MM patients. Baseline cardiovascular (CV) comorbidities, incidence rate of hypertension and malignant hypertension in the follow-up period, and risk of hypertension and malignant hypertension based on existing baseline CV comorbidities were evaluated. RESULTS: A total of 7895 MM patients (38% with hypertension history) and 23,685 non-MM patients (24% with hypertension history) were included in the study. Twenty-two percent of MM patients versus 3% of non-MM patients had baseline renal failure. A higher percentage of MM versus non-MM patients had baseline hypertension in combination with renal failure, congestive heart failure or both. The incidence rate of hypertension in MM and non-MM patients was 260 and 178 per 1000 person-years, respectively. There was a 30% increase in the risk of hypertension for MM versus non-MM patients: hazard ratio (HR) 1.30 (95% confidence interval [CI] 1.22, 1.37). In MM patients with a history of hypertension, the risk of malignant hypertension was significantly increased with the following comorbid conditions: cardiomyopathy, HR 2.79 (95% CI 1.20, 6.48); renal failure, HR 2.13 (95% CI 1.36, 3.34); and diabetes mellitus, HR 1.59 (95% CI 1.05, 2.39). CONCLUSIONS: This study confirms that the incidence of hypertension and malignant hypertension is significantly higher in newly-treated MM versus non-MM patients. Hypertension is a risk factor for MM patients developing malignant hypertension. Management of CV comorbidities in MM patients is important based on the increased risk of hypertension and malignant hypertension among patients with these comorbidities.

Patient population with multiple myeloma and transitions across different lines of therapy in the USA: an epidemiologic model.

PURPOSE: Multiple myeloma (MM) is a progressive, malignant neoplasia with a worldwide, age-standardized annual incidence of 1.5 per 100 000 individuals and 5-year prevalence around 230 000 patients. Main favorable prognostic factors are younger age, low/standard cytogenetic risk, and undergoing stem cell transplantation. Our aim was to estimate the size of the patient population with MM eligible to receive a new MM therapy at different lines of therapy in the USA. METHODS: We constructed a compartmental, differential equation model representing the flow of MM patients from diagnosis to death, via two possible treatment pathways and distinguished in four groups based on prognostic factors. Parameters were obtained from published references, available statistics, and assumptions. The model was used to estimate number of diagnosed MM patients and number of patient transitions from one line of therapy to the next over 1 year. Model output included 95% credible intervals from probabilistic sensitivity analyses. RESULTS: The base-case estimates were 80 219 patients living with MM, including 70 375 on treatment, 780 symptomatic untreated patients, and 9064 asymptomatic untreated patients. Over a 1-year period, the number of MM patients on treatment line 1 was estimated at 23 629 (credible intervals 22 236-25 029), and the number of transitions from treatment line 1 to treatment line 2 was estimated at 14 423. CONCLUSIONS: The size of the patient population with MM on different lines of therapy and in patient subgroups of interest estimated from this epidemiologic model can be used to assess the number of patients who could benefit from new MM therapies and their corresponding budgetary impact. Copyright © 2016 John Wiley & Sons, Ltd.

A temporal and multinational assessment of acute myeloid leukemia (AML) cancer incidence, survival, and disease burden.

Understanding the global epidemiology of AML is critical for assessing therapeutic demand and informing healthcare resource allocation. This study estimated current and future AML incidence in 27 countries, described AML survival trends in the United States, and calculated average years of life lost (AYLL). Incidence rates were age-standardized using rates from IARC's Cancer Incidence in Five Continents and SEER databases and ranged from 0.70 to 3.23 cases per 100,000 persons. Crude incidence rates were projected from 2024 to 2040; growth varied from +1% to +46%. Median overall survival was derived from SEER databases and increased from 4 to 11 months over the last 40 years. Median AYLL of 18.6 years was estimated for 27 countries. This study projected significant growth in new AML diagnoses over the next two decades. Despite improvements in survival over the last four decades, median survival among AML patients remains poor highlighting the need for novel treatments.

Hospitalized cardiovascular events in patients with diabetic macular edema.

BACKGROUND: Microvascular and macrovascular complications in diabetes stem from chronic hyperglycemia and are thought to have overlapping pathophysiology. The aim of this study was to investigate the incidence rate of hospitalized myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with diabetic macular edema (DME) compared with diabetic patients without retinal diseases. METHODS: This was a retrospective cohort study of a commercially insured population in an administrative claims database. DME subjects (n = 3519) and diabetes controls without retinal disease (n = 10557) were matched by age and gender. Healthcare claims were analyzed for the study period from 1 January 2002 to 31 December 2005. Incidence and adjusted rate ratios of hospitalized MI and CVA events were then calculated. RESULTS: The adjusted rate ratio for MI was 2.50 (95% CI: 1.83-3.41, p < 0.001) for DME versus diabetes controls. Predictors of MI events were heart disease, history of acute MI, and prior use of antiplatelet or anticoagulant drugs. The adjusted rate ratio for CVA was 1.98 (95% CI: 1.39-2.83, p < 0.001) for DME versus diabetes controls. Predictors of CVA events were cardiac arrhythmia, Charlson comorbidity scores, history of CVA, hyperlipidemia, and other cerebrovascular diseases. CONCLUSION: Event rates of MI or CVA were higher in patients with DME than in diabetes controls. This study is one of few with sufficient sample size to accurately estimate the relationship between DME and cardiovascular outcomes.

Validation of ICD-9-CM codes to identify gastrointestinal perforation events in administrative claims data among hospitalized rheumatoid arthritis patients.

PURPOSE: To validate, using physician review of abstracted medical chart data as a gold standard, a claims-based algorithm developed to identify gastrointestinal (GI) perforation cases among rheumatoid arthritis (RA) patients. METHODS: Patients with established RA, aged 18 years or older with hospital admissions between January 2004 and September 2009, were selected from a large US-hospital-based database. An algorithm with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes for GI perforation and combinations of GI-related diagnosis codes and Current Procedural Terminology (CPT-4) procedure codes for relevant GI surgeries was used to identify potential GI perforation cases. Two senior experienced specialist physicians independently reviewed abstracted chart data and classified cases as confirmed or unconfirmed GI perforations. Positive predictive values (PPVs) to identify confirmed GI perforation were calculated and stratified by upper versus lower GI tract. RESULTS: Overall, 86 of 92 GI perforation cases were confirmed, yielding an overall PPV of 94% (95%confidence interval [CI] = 86%-98%). PPV was 100% (95%CI = 100%-100%) for upper GI perforation (esophagus, stomach) and 91% (95%CI = 90%-97%) for lower GI perforation (small intestine, PPV = 100%; large intestine, PPV = 94%; unspecified lower GI, PPV = 89%). CONCLUSIONS: This algorithm, consisting of a combination of ICD-9-CM diagnosis and CPT-4 codes, could be used in future safety studies to evaluate GI perforation risk factors in RA patients.

Mortality by a proxy performance status as defined by a claims-based measure for disability status in older patients with newly diagnosed multiple myeloma in the United States.

OBJECTIVES: We applied a claims-based definition of disability status as a proxy for performance status (PS) and examined associations between PS and mortality in a population-based cohort of older US adults with multiple myeloma (MM). MATERIALS AND METHODS: We identified older (≥66 years) Medicare beneficiaries diagnosed with MM January 1, 2008-December 31, 2011, who began first-line therapy in the study period (through December 31, 2012). We estimated predicted probability of poor PS for each patient at initiation of each line up to fourth-line therapy, classified as poor (predicted probability ≥0.11) or good (<0.11) PS, and examined mortality. Crude overall survival was estimated using the Kaplan-Meier method with log-rank test for survival comparison between PS groups. Cox proportional hazards models evaluated the association between poor PS and mortality risk, adjusted for baseline characteristics by lines of therapy. RESULTS: Of 12,547 patients, 5841, 2372, and 819 initiated second-, third-, and fourth-line in the study period. Poor PS proportions were 16.6%, 21.8%, 18.4%, and 18.2% at each line. Crude overall survival was worse for poor PS patients across lines (P < 0.01 for each). Adjusted hazards ratios (95% CI) of mortality for patients with poor versus good PS were 1.28 (1.18-1.40), first-line; 1.55 (1.36-1.77), second-line; 1.35 (1.10-1.65), third-line; 1.22 (0.84-1.76), fourth-line. CONCLUSION: The claims-based prediction model for disability status performed as expected as a proxy for PS in older Medicare patients with MM. PS was an independent risk factor for mortality. Further studies assessing the effect of PS on mortality by therapies are warranted.

Annual rates of arterial thromboembolic events in medicare neovascular age-related macular degeneration patients.

PURPOSE: Smoking, age, and nutrition have been associated with the development of neovascular age-related macular degeneration (AMD) and can increase the risk of arterial thromboembolic events (ATEs). This study assesses annual rates of ATEs in new-onset neovascular AMD patients compared with matched controls. DESIGN: Retrospective study. PARTICIPANTS: New-onset neovascular AMD patients and age-, race-, gender-, and database length-matched controls from the 5% Medicare database. METHODS: We conducted a retrospective analysis of the 5% Medicare database from 2001 to 2003. New-onset neovascular AMD patients were included if they were > or =65 years old, had 2 diagnoses of neovascular AMD, and had at least 1 year of data before the first diagnosis of AMD within the dataset. A control group was constructed in a 3:1 ratio from those without a diagnosis of a major eye disorder and matched by age, race, gender, and length of data. Annual prevalence rates were determined for myocardial infarctions (MIs) and ischemic cerebral vascular accidents (CVAs). MAIN OUTCOME MEASURES: Rates of MIs and ischemic CVAs in new-onset neovascular AMD patients and matched controls from 2001 to 2003. RESULTS: There were 15771 new-onset neovascular AMD patients identified and matched with 46 408 controls. Average age was 80.5 years, with 64% > or =80; 65% were female; and 95.9% were white. Inpatient MI rates for neovascular AMD patients and controls were 2.2% and 2.2%, respectively (P = 0.74). Inpatient ischemic CVA rates for neovascular AMD patients and controls were 3.5% and 3.6%, respectively (P = 0.59). Myocardial infarction rates and ischemic CVA rates for both groups increased with age. Subgroups of patients with comorbidities known to be risk factors for ATEs (i.e., hypertension, hyperlipidemia, diabetes, and arrhythmias) had a higher rate of events. Patients with previous ATEs were also at a higher risk of subsequent events, at 7.4% for inpatient MI and 35.1% for inpatient ischemic stroke. CONCLUSION: Despite the shared risk factors associated with neovascular AMD and ATEs, Medicare beneficiaries with neovascular AMD had a rate of ATEs similar to that of matched controls. Rates of ATEs increased in patients with comorbidities and for patients with previous events.

Incidence and Risk of Cardiac Events in Patients With Previously Treated Multiple Myeloma Versus Matched Patients Without Multiple Myeloma: An Observational, Retrospective, Cohort Study.

BACKGROUND: Multiple myeloma (MM) patients have age-, disease-, and treatment-related risk factors for cardiac events. MATERIALS AND METHODS: We analyzed the 2006 to 2011 MarketScan database to determine whether the risk of cardiac events is greater in MM patients than in non-MM patients. Included were 1723 MM patients treated with corticosteroids and ≥ 3 drugs (bortezomib, immunomodulatory derivatives, and alkylating agents or anthracyclines). The index date (ID) was the date on which the 3-drug exposure criterion was met. Also included were 8615 age- and gender-matched non-MM patients (5:1). The distribution of non-MM patients' IDs matched that of the MM patients' IDs. Baseline was 6 months before the ID. The follow-up duration was from the ID to study end (ie, 2011 or end of enrollment or prescription drug coverage). Hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for baseline variables when the univariate analyses showed a 10% difference. RESULTS: The median duration of observation was 9 months (range, 0-60 months) for MM patients and 19 months (range, 0-66 months) for non-MM patients. The risk of any cardiac event (HR, 2.2; 95% CI, 1.9-2.5), dysrhythmia (HR, 4.1; 95% CI, 3.5-4.8), congestive heart failure (HR, 2.9; 95% CI, 2.2-3.7), cardiomyopathy (HR, 2.6; 95% CI, 1.8-3.8), and conduction disorders (HR, 1.7; 95% CI, 1.2-2.5) was significantly greater for MM than for non-MM patients. The incidence of hypertensive or arterial events and ischemic heart disease was similar between the 2 groups. CONCLUSION: The present study provides the first known comparison of cardiac event risk in patients with MM versus age- and gender-matched patients without MM. The cardiac event risk was greater in MM patients with ≥ 3 previous drugs for any cardiac event, dysrhythmias, congestive heart failure, cardiomyopathy, and conduction disorders compared with patients without MM.

Development and Validation of an Algorithm to Identify Patients with Multiple Myeloma Using Administrative Claims Data.

PURPOSE: The objective was to expand on prior work by developing and validating a new algorithm to identify multiple myeloma (MM) patients in administrative claims. METHODS: Two files were constructed to select MM cases from MarketScan Oncology Electronic Medical Records (EMR) and controls from the MarketScan Primary Care EMR during January 1, 2000-March 31, 2014. Patients were linked to MarketScan claims databases, and files were merged. Eligible cases were age ≥18, had a diagnosis and visit for MM in the Oncology EMR, and were continuously enrolled in claims for ≥90 days preceding and ≥30 days after diagnosis. Controls were age ≥18, had ≥12 months of overlap in claims enrollment (observation period) in the Primary Care EMR and ≥1 claim with an ICD-9-CM diagnosis code of MM (203.0×) during that time. Controls were excluded if they had chemotherapy; stem cell transplant; or text documentation of MM in the EMR during the observation period. A split sample was used to develop and validate algorithms. A maximum of 180 days prior to and following each MM diagnosis was used to identify events in the diagnostic process. Of 20 algorithms explored, the baseline algorithm of 2 MM diagnoses and the 3 best performing were validated. Values for sensitivity, specificity, and positive predictive value (PPV) were calculated. CONCLUSION: Three claims-based algorithms were validated with ~10% improvement in PPV (87-94%) over prior work (81%) and the baseline algorithm (76%) and can be considered for future research. Consistent with prior work, it was found that MM diagnoses before and after tests were needed.

A retrospective analysis to examine factors associated with mortality in Medicare beneficiaries newly diagnosed with multiple myeloma.

OBJECTIVE: Population-based data on mortality and associated factors in patients with multiple myeloma (MM) are limited. We examined the association between all-cause mortality and demographic and clinical characteristics in newly diagnosed MM patients treated with guideline-recommended chemotherapeutic agents. RESEARCH DESIGN AND METHODS: This retrospective cohort analysis used Medicare 20% data to create a cohort of adult (aged ≥18 years) newly diagnosed MM patients who received chemotherapy 2008-2011 and had no MM diagnosis in the 12 months before the disease index date. Patients were followed from treatment initiation through the earliest of death, loss of insurance coverage, or study end (December 2011). Modified Charlson Comorbidity Index scores and MM-related comorbid conditions (anemia, hypercalcemia, skeletal-related events) were identified in the 6 month pre-index-date period. All-cause mortality and associated factors were examined using multivariable Cox proportional hazard models. RESULTS: We identified 2419 newly diagnosed patients who received MM therapy during follow-up. Mean (SD) and median follow-up were 1.51 (1.0) and 1.37 years. Of the cohort, 55% were female, 78% white, and 92% aged ≥65 years. Pre-index, 54%, 9%, and 5% were diagnosed with anemia, hypercalcemia, and skeletal-related events. Overall, 942 (39%) patients died during follow-up. Factors associated with increased risk of death were older age (≥65 vs. 18-64 years; hazard ratio 1.49, 95% confidence interval 1.13-1.99), higher comorbidity score (≥4 vs. 0; 1.78, 1.43-2.21), anemia (1.23, 1.06-1.42), and hypercalcemia (1.45, 1.19-1.76); female sex (0.86, 0.75-0.98) was associated with decreased risk. CONCLUSIONS: Older age, male sex, high comorbidity burden, anemia, and hypercalcemia were risk factors for death in newly diagnosed Medicare MM patients. Study limitations included non-causal observational design, non-validated MM algorithm, potential treatment misclassification, and non-availability of prognostic factors including disease staging information, biomarkers, and other laboratory variables. Additional analyses are warranted to understand the relationship between treatments and death.

Myocardial infarction and cerebrovascular accident in patients with retinal vein occlusion.

OBJECTIVE: To compare the incidence rates of myocardial infarction (MI) and cerebrovascular accident (CVA) in hospitalized patients with and without branch or central retinal vein occlusion (RVO). METHODS: In this retrospective cohort study, a US population-based health care claims database was used to identify patients with RVO and control patients, matched for age and sex. Events of MI, CVA, and covariates were identified for patients with and without RVO. Incidences of MI or CVA events prompting hospitalization and adjusted rate ratios (RRs) were calculated; RRs were adjusted for covariates consistent with risk factors for outcomes. RESULTS: Of 4500 patients with RVO and 13,500 controls, the event rates for MI were 0.87 per 100 person-years and 0.67 per 100 person-years, respectively. The adjusted RR for MI was 1.03 (95% confidence interval [CI], 0.75-1.42; P = .85 for RVO vs controls). Event rates for CVA were 1.16 and 0.52 per 100 person-years for RVO and controls, respectively. The adjusted RR for CVA was 1.72 (95% CI, 1.27-2.34; P = .001) for RVO vs controls. CONCLUSIONS: This study provides quantitative data on the incidence of cardiovascular and cerebrovascular outcomes in patients with RVO in a large US population-based health care claims database. Event rates for MI were similar in patients with RVO and controls; however, the event rate for CVA in patients with RVO was almost 2-fold that observed in controls.

Hospitalized cardiovascular diseases in neovascular age-related macular degeneration.

OBJECTIVE: To compare the incidence rate of hospitalized myocardial infarctions (MIs) and cerebrovascular accidents (CVAs) in subjects with and without neovascular age-related macular degeneration (AMD). METHODS: A retrospective database cohort study was performed in subjects with neovascular AMD and controls matched for age, sex, geography, and enrollment duration. Healthcare claims for the study period from January 1, 2002, to June 30, 2005, were used to identify subjects and outcomes. Incidence of hospitalized MI and CVA events and rate ratios adjusted for 11 risk factors were calculated. RESULTS: In 7203 subjects with neovascular AMD and 20,208 controls, the rate of MI was 16.2 events per 1000 subjects with neovascular AMD and 23.1 events per 1000 controls. The adjusted rate ratio for MI was 0.58 (95% confidence interval, 0.48-0.72; P < .001) for subjects with neovascular AMD vs controls. The rate of CVA was 14.3 events per 1000 subjects with neovascular AMD and 22.1 events per 1000 controls. The adjusted rate ratio for CVA was 0.56 (95% confidence interval, 0.45-0.70; P < .001). CONCLUSIONS: Rates of MI or CVA were significantly lower in subjects with neovascular AMD than in controls. These findings could not be explained by systematic differences in case selection, health care use, or comorbidities, although other possible biases cannot be ruled out.

A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis.

BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population. METHODS: Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population. RESULTS: The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases. CONCLUSIONS: These results suggest that efalizumab treatment does not increase a patient's risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.