Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis.

BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study.

BACKGROUND: Despite recent advances in therapeutic options, there remains an unmet need for treating patients with relapsed or refractory multiple myeloma, especially in those previously exposed or refractory to lenalidomide. This updated efficacy and safety analysis from the phase 3 CANDOR study compared carfilzomib, daratumumab, and dexamethasone (KdD) with carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma. METHODS: In this updated analysis of the randomised, multicentre, open-label, phase 3 CANDOR study, patients (aged ≥18 years) with relapsed or refractory multiple myeloma, at least a partial response to between one and three previous therapies, and Eastern Cooperative Oncology Group performance status of 0-2, were recruited from 102 medical centres globally and randomly assigned (2:1) by interactive voice or web response software to receive KdD or Kd. Participants were stratified by disease stage, previous proteasome inhibitor or anti-CD38 antibody exposure, and number of previous therapies. All patients received intravenous infusions of carfilzomib twice per week at 56 mg/m2 (20 mg/m2 on days 1 and 2 during cycle 1) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Daratumumab (8 mg/kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first two cycles, then every 2 weeks for four cycles (cycles 3-6), and every 4 weeks thereafter. Patients received 40 mg dexamethasone weekly (20 mg for patients >75 years old). This analysis was a preplanned interim analysis for overall survival; however, at the time of data cutoff, overall survival data were not mature. The primary endpoint was progression-free survival. Here, we provide updated progression-free survival data, assessed centrally by Onyx Response Computer Algorithm in the intention-to-treat population, with 11 months additional follow-up. Adverse events were assessed in the safety population, which included all participants who received at least one dose of trial treatment. CANDOR is registered with ClinicalTrials.gov, NCT03158688, and is active but not recruiting. FINDINGS: Between June 13, 2017, and June 25, 2018, 466 patients were enrolled, of whom 312 received KdD and 154 received Kd. At data cutoff (June 15, 2020), median follow-up was 27·8 months (IQR 25·6-29·5) for KdD and 27·0 months (13·2-28·6) for Kd. Median progression-free survival was 28·6 months (95% CI 22·7-not estimable [NE]) in the KdD group and 15·2 months (11·1-19·9) in the Kd group (hazard ratio 0·59 [95% CI 0·45-0·78], log-rank p<0·0001). Treatment-emergent adverse events in the safety population were consistent with the primary analysis. Grade 3 or worse treatment-emergent adverse events occurred in 268 (87%) patients in the KdD group and 116 (76%) in the Kd group; most commonly thrombocytopenia (76 [25%] vs 25 [16%], respectively), hypertension (65 [21%] vs 23 [15%]), pneumonia (54 [18%] vs 14 [9%]), and anaemia (53 [17%] vs 23 [15%]). Serious adverse events occurred in 194 (63%) patients with KdD and 76 (50%) with Kd. Adverse events leading to death occurred in 27 (9%) patients in the KdD group and seven (5%) in the Kd group; most commonly septic shock (five [2%] vs one (1%]) and pneumonia (four [1%] vs none). No new treatment-related deaths have occurred since the primary analysis. INTERPRETATION: A clear, maintained progression-free survival benefit of KdD over Kd with longer follow-up was confirmed, making KdD an emerging standard-of-care for patients with relapsed or refractory multiple myeloma. FUNDING: Amgen and Janssen.

Risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments: An observational cohort study.

INTRODUCTION: This study quantified risks of cardiovascular, cerebrovascular, and mortality events among patients with migraine receiving prophylaxis. METHODS: Patients with migraine aged 18-65 years were identified from 2010 through 2015 within a United States administrative claims database. Topiramate initiators during follow-up were propensity score-matched separately to anticonvulsant, cardiovascular treatment, antidepressant, and other prophylactic treatment initiators. Incident outcomes were identified, and hazard ratios were calculated comparing outcome occurrence among topiramate initiators relative to each comparator. A case-control analysis was nested within the full migraine cohort, and odds ratios quantified the association between outcomes and use or non-use of individual prophylactic treatments (anticonvulsants, serotonin norepinephrine reuptake inhibitors, beta blockers, antihypertensives, tricyclic antidepressants, and other prophylactic treatments). RESULTS: The cohort included 119,243 patients with migraine. The matched topiramate initiators had a lower mortality risk versus antidepressant (hazard ratio: 0.44, 95% CI: 0.24, 0.83) and anticonvulsant initiators (hazard ratio: 0.45, 95% CI: 0.25, 0.84). In the case-control analysis, increased risks of several outcomes were observed with all prophylactic treatments relative to non-use of that treatment (odds ratios range from 1.54 to 7.90, and 95% CIs exclude 1.0) except for topiramate and calcium channel blockers. CONCLUSIONS: Although increased risks for several outcomes were observed with certain prophylactic treatments, the treatments other than topiramate likely represent markers for outcome risk factors that developed or progressed after cohort entry, rather than being a direct effect of the treatments. Factors including migraine severity, frequency, and other treatment indications should be considered in future migraine prophylactic treatment safety assessments.

Use of existing electronic health care databases to evaluate medication safety in pregnancy: Triptan exposure in pregnancy as a case study.

PURPOSE: The recent expansion of electronic health and medical record systems may present an opportunity to generate robust post-approval safety data and obviate the limitations of prospective pregnancy exposure registries. We examined and compared, over the same time frame, the outcomes of triptan exposure in pregnancy using (1) a retrospective claims database and (2) a previously completed pregnancy registry. METHODS: Using the Marketscan database, the risk of major birth defects was ascertained in live-born infants whose birth mothers were exposed to sumatriptan, naratriptan, or sumatriptan/naproxen during pregnancy. The frequencies of outcomes observed were compared with the findings of the 16-year sumatriptan, naratripan, and sumatriptan/naproxen prospective pregnancy registry. RESULTS: About 5120 pregnancies were identified in the retrospective claims cohort in contrast to 617 included in the prospective registry during the same time frame. The proportion of major birth defects among first-semester sumatriptan exposures was 4.0%, which is exactly the same as the proportion of major birth defects reported for first-semester sumatriptan exposures in the registry. There were very few non-livebirth outcomes in both the claims analyses and registry. CONCLUSIONS: These results confirm broad agreement between the database analysis and the registry regarding the safety of triptans during pregnancy. Of note, the number of triptan-exposed pregnancies identified in this large US database was about 7-fold that included in the prospective registry over the same time frame. The findings of this study support an approach of using existing health care database (s) in the post-approval assessment of medication exposure in pregnancy.

Serum Potassium Levels and Mortality in Hemodialysis Patients: A Retrospective Cohort Study.

BACKGROUND: Hyperkalemia is common in patients receiving maintenance hemodialysis. However, few studies have examined the association between serum potassium level and mortality. METHODS: This study used annual cohorts of hemodialysis patients during 2007-2010. To determine hyperkalemia prevalence, monthly hyperkalemia was defined as serum potassium level ≥5.5 mEq/l; prevalence was calculated as a ratio of hyperkalemia episodes to follow-up time, reported separately by long and short interdialytic interval. To determine the impact of hyperkalemia on mortality, patients in the 2010 cohort were followed from first potassium measurement until death or a censoring event; hyperkalemia was defined, sequentially, by potassium levels 5.5-6.0 mEq/l at 0.1 mEq/l intervals. Time-dependent Cox proportional hazards modeling was used to estimate the association between hyperkalemia and mortality. RESULTS: The 4 annual cohorts ranged from 28,774 to 36,888 patients. Mean age was approximately 63 years, about 56% were men, 51% were white and 44% had end-stage renal disease caused by diabetes. Hyperkalemia prevalence was consistently estimated at 16.3-16.8 events per 100 patient-months. Prevalence on the day after the long interdialytic interval was 2.0-2.4 times as high as on the day after the short interval. Hyperkalemia, when defined as serum potassium ≥5.7 mEq/l, was associated with all-cause mortality (adjusted hazards ratio (AHR) 1.13, 95% CI 1.01-1.28, p = 0.037, vs. <5.7 mEq/l) after adjustment. AHRs increased progressively as the hyperkalemia threshold increased, reaching 1.37 (95% CI 1.16-1.62, p < 0.0001) for ≥6.0 mEq/l. CONCLUSIONS: The long interdialytic interval was associated with increased likelihood of hyperkalemia. Hyperkalemia was associated with all-cause mortality beginning at serum potassium ≥5.7 mEq/l; mortality risk estimates increased ordinally through ≥6.0 mEq/l, suggesting a threshold at which serum potassium becomes substantially more dangerous.

Facility-level CKD-MBD composite score and risk of adverse clinical outcomes among patients on hemodialysis.

BACKGROUND: Patients receiving hemodialysis with values outside of target levels for parathyroid hormone (PTH: 150-600 pg/mL), calcium (Ca: 8.4-10.2 mg/dL), and phosphate (P: 3.5-5.5 mg/dL) are at elevated morbidity and mortality risk. We examined whether patients receiving care in dialysis facilities where greater proportions of patients have at least two values out of target have a higher risk of adverse clinical outcomes. METHODS: The study cohort consisted of 39,085 prevalent hemodialysis patients in 1298 DaVita dialysis facilities as of September 1, 2009, followed from January 1, 2010, until an outcome, a censoring event, or December 31, 2010. We determined the quintile of the distribution across facilities of the proportion of patients with at least two of three parameters out of, or above, target over a 4-month baseline period. The primary composite outcome was cardiovascular hospitalization or death. Secondary outcomes included death, cardiovascular hospitalization, and parathyroidectomy. Poisson regression models were used to estimate the association of facility quintile with outcomes. RESULTS: Facility quintile was associated with a 7 % increased risk of cardiovascular hospitalization or death (quintile 5 versus 1, RR 1.07, 95 % CI 1.01-1.13) using the out-of-target measure of exposure and a 12 % increased risk (RR 1.12, 95 % CI 1.06-1.19) using the above-target measure. No association was seen for death using either measure. Patients in facility quintiles 3-5 (versus 1) were at increased parathyroidectomy risk (RR ranged from 2.05, 95 % CI 1.10-3.82, for quintile 3 to 2.73, 95 % CI 1.50-4.98, for quintile 5). CONCLUSIONS: Facility level analysis of a large prevalent sample of US patients on hemodialysis demonstrates that patients in facilities with the least control of PTH, Ca, and P had the greatest risk of parathyroidectomy or the combination of cardiovascular hospitalization or death.

Parathyroid hormone change after cinacalcet initiation and one-year clinical outcome risk: a retrospective cohort study.

BACKGROUND: Cinacalcet reduces parathyroid hormone (PTH) levels in patients receiving hemodialysis, but no non-experimental studies have evaluated the association between changes in PTH levels following cinacalcet initiation and clinical outcomes. We assessed whether short-term change in PTH levels after first cinacalcet prescription could serve as a surrogate marker for improvements in longer-term clinical outcomes. METHODS: United States Renal Data System data were linked with data from a large dialysis organization. We created a point prevalent cohort of adult hemodialysis patients with Medicare as primary payer who initiated cinacalcet November 1, 2004-February 1, 2007, and were on cinacalcet for ≥ 40 days. We grouped patients into quartiles of PTH change after first cinacalcet prescription. We used Cox proportional hazard modeling to evaluate associations between short-term PTH change and time to first composite event (hospitalization for cardiovascular events or mortality) within 1 year. Overall models and models stratified by baseline PTH levels were adjusted for several patient-related factors. RESULTS: For 2485 of 3467 included patients (72%), PTH levels decreased after first cinacalcet prescription; for 982 (28%), levels increased or were unchanged. Several characteristics differed between PTH change groups, including age and mineral-and-bone-disorder laboratory values. In adjusted models, we did not identify an association between greater short-term PTH reduction and lower composite event rates within 1 year, overall or in models stratified by baseline PTH levels. CONCLUSIONS: Short-term change in PTH levels after first cinacalcet prescription does not appear to be a useful surrogate for longer-term improvements in cardiovascular or survival risk.

Comparative effectiveness of calcium acetate and sevelamer on clinical outcomes in elderly hemodialysis patients enrolled in Medicare part D.

BACKGROUND: Phosphate binders are an important therapeutic option for managing hyperphosphatemia in hemodialysis patients. Whether sevelamer confers a survival advantage over calcium acetate is unclear. STUDY DESIGN: Observational cohort study using US Renal Data System (USRDS) data linked to Medicare Part D prescription drug data. SETTING & PARTICIPANTS: Medicare-enrolled elderly incident hemodialysis patients initiating calcium acetate or sevelamer therapy between July 1, 2006, and March 31, 2011. PREDICTOR: Prescription for sevelamer (hydrochloride or carbonate) or calcium acetate. OUTCOMES & MEASUREMENTS: All-cause and cardiovascular-related mortality, hospital admissions and hospital days assessed from Medicare Parts A, B, and D claims and other USRDS data. RESULTS: The sevelamer and calcium-acetate groups included 16,916 and 18,335 patients, respectively. After multivariable adjustment, all-cause (21.9 vs 21.8 deaths/100 patient-years; adjusted HR, 0.97; 95% CI, 0.94-1.03) and cardiovascular (8.7 vs 8.6 deaths/100 patient-years; HR, 0.99; 95% CI, 0.93-1.04) mortality did not differ significantly between the sevelamer and calcium-acetate (referent) groups. Mortality results in propensity score-matched cohorts showed significantly lower risk of death in sevelamer- than in calcium-acetate-treated patients (HR, 0.94; 95% CI, 0.91-0.98). Mortality results from additional analyses including only patients with low-income subsidy status were consistent with results from analyses including patients with and without low-income subsidy status. There were no significant differences between the sevelamer and calcium-acetate groups for all-cause and cardiovascular-related first hospitalization, multiple hospitalizations, and hospital days. LIMITATIONS: Results may not be applicable to younger patients; information about laboratory data and over-the-counter calcium-containing binders was lacking. CONCLUSIONS: Relative to treatment with calcium acetate, treatment with sevelamer was associated with similar or slightly lower risk of death and similar risk of hospitalization in elderly incident hemodialysis patients.

Utilization and costs of medications associated with CKD mineral and bone disorder in dialysis patients enrolled in Medicare Part D.

BACKGROUND: Information is limited regarding utilization patterns and costs for chronic kidney disease-mineral and bone disorder (CKD-MBD) medications in Medicare Part D-enrolled dialysis patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Annual cohorts of dialysis patients, 2007-2010. PREDICTORS: Cohort year, low-income subsidy status, and dialysis provider. OUTCOMES: Utilization and costs of prescription phosphate binders, oral and intravenous vitamin D analogues, and cinacalcet. MEASUREMENTS: Using logistic regression, we calculated adjusted odds of medication use for low-income subsidy versus non-low-income subsidy patients and for patients from various dialysis organizations, and we report per-member-per-month and average out-of-pocket costs. RESULTS: Phosphate binders (∼83%) and intravenous vitamin D (77.5%-79.3%) were the most commonly used CKD-MBD medications in 2007 through 2010. The adjusted odds of prescription phosphate-binder, intravenous vitamin D, and cinacalcet use were significantly higher for low-income subsidy than for non-low-income subsidy patients. Total Part D versus CKD-MBD Part D medication costs increased 22% versus 36% from 2007 to 2010. For Part D-enrolled dialysis patients, CKD-MBD medications represented ∼50% of overall net Part D costs in 2010. LIMITATIONS: Inability to describe utilization and costs of calcium carbonate, an over-the-counter agent not covered under Medicare Part D; inability to reliably identify prescriptions filled through a non-Part D reimbursement or payment mechanism; findings may not apply to dialysis patients without Medicare Part D benefits or with Medicare Advantage plans, or to pediatric dialysis patients; could identify only prescription drugs dispensed in the outpatient setting; inability to adjust for MBD laboratory values. CONCLUSIONS: Part D net costs for CKD-MBD medications increased at a faster rate than costs for all Part D medications in dialysis patients despite relatively stable use within medication classes. In a bundled environment, there may be incentives to shift to generic phosphate binders and reduce cinacalcet use.

Carfilzomib 56 mg/m2 twice-weekly in combination with dexamethasone and daratumumab (KdD) versus daratumumab in combination with bortezomib and dexamethasone (DVd): a matching-adjusted indirect treatment comparison.

Given the increasing use of frontline lenalidomide-based therapies in multiple myeloma (MM), there is an emerging need for lenalidomide-sparing regimens at relapse. Carfilzomib plus dexamethasone and daratumumab (KdD) and daratumumab plus bortezomib and dexamethasone (DVd) are lenalidomide-sparing triplet regimens that are approved for relapsed and/or refractory MM (R/RMM). In the absence of a head-to-head trial comparing these treatments, a matching-adjusted indirect treatment comparison (MAIC) was conducted to assess the efficacy and safety of KdD versus DVd. Results showed that treatment with KdD decreases the risk of progression or death versus DVd (HR 0.64; 95% confidence interval (CI): 0.46-0.90). Time-dependent analysis demonstrated a larger benefit for KdD after the first eight cycles. Unmatched subgroup analysis indicated that KdD may be particularly effective in lenalidomide-exposed and -refractory patients. The present analysis suggests that KdD improves outcomes compared with DVd in patients with R/RMM and may provide a rationale for a preferential treatment.

A combination of carfilzomib, dexamethasone, and daratumumab for treatment of adult patients with relapsed/refractory multiple myeloma in two dosing regimens: once-weekly and twice-weekly.

INTRODUCTION: Despite the development of new therapeutic agents, relapsed/refractory multiple myeloma (RRMM) is associated with poor survival outcomes. Furthermore, many patients develop resistance to immunomodulatory drugs (IMiD), creating a need for IMiD-free regimens. Areas covered: This review focuses on the combination of carfilzomib, dexamethasone, and daratumumab (KdD or DKd) which has shown promising results in patients with RRMM who have tried multiple lines of therapy, and has been approved in the U.S., EU, and Japan. The KdD triplet has two recommended dosage regimens, carfilzomib once-weekly (KdD70 QW) and carfilzomib twice-weekly (KdD56 BIW), with comparable efficacy and safety profiles. Expert opinion: These options provide flexibility to patients and healthcare providers, especially in the era of COVID-19. Carfilzomib-based regimens remain a standard of care based on multiple randomized phase 3 studies. Additional studies are currently underway investigating carfilzomib-based regimens such as KdD combined with novel agents. Nevertheless, KdD is one of the most efficacious options for patients with RRMM.

Predictors of imminent risk of fracture in Medicare-enrolled men and women.

Advancing age, female sex, recent prior fracture and falls, and specific comorbidities and medications contribute to imminent (within 1-2 years) risk of fracture in Medicare enrollees. Clinician awareness of these risk factors and their dynamic nature may lead to improved osteoporosis care for elderly patients. PURPOSE: The burden of osteoporotic fracture disproportionately affects the elderly. Growing awareness that fracture risk can change substantially over time underscores the need to understand risk factors for imminent (within 1-2 years) fracture. This study assessed predictors of imminent risk of fracture in the US Medicare population. METHODS: Administrative claims data from a random sample of Medicare beneficiaries were analyzed for patients aged ≥ 67 years on January 1, 2011 (index date), with continuous coverage between January 1, 2009 and March 31, 2011, excluding patients with non-melanoma cancer or Paget's disease. Incident osteoporotic fractures were identified during 12 and 24 months post-index. Potential predictors were age, sex, race, history of fracture, history of falls, presence of osteoporosis, cardiovascular diseases, chronic obstructive pulmonary disorder (COPD), mood/anxiety disorders, polyinflammatory conditions, difficulty walking, use of durable medical equipment, ambulance/life support, and pre-index use of osteoporosis medications, steroids, or central nervous system medications. Cox proportional hazards models were used to evaluate predictors of fracture risk in the two follow-up intervals. RESULTS: Among 1,780,451 individuals included (mean age 77.7 years, 66% female), 8.3% had prior fracture and 6.1% had a history of falls. During the 12- and 24-month follow-up periods, 3.0% and 5.4% of patients had an incident osteoporotic fracture, respectively. Imminent risk of fracture increased with older age (double/triple), female sex (> 80%), recent prior fracture (> double) and falls, and specific comorbidities and medications. CONCLUSIONS: Demographics and factors including fall/fracture history, comorbidities, and medications contribute to imminent risk of fracture in elderly patients.

Evaluation of claims-based computable phenotypes to identify heart failure patients with preserved ejection fraction.

The purpose of this analysis was to develop and validate computable phenotypes for heart failure (HF) with preserved ejection fraction (HFpEF) using claims-type measures using the Rochester Epidemiology Project. This retrospective study utilized an existing cohort of Olmsted County, Minnesota residents aged ≥ 20 years diagnosed with HF between 2007 and 2015. The gold standard definition of HFpEF included meeting the validated Framingham criteria for HF and having an LVEF ≥ 50%. Computable phenotypes of claims-type data elements (including ICD-9/ICD-10 diagnostic codes and lab test codes) both individually and in combinations were assessed via sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with respect to the gold standard. In the Framingham-validated cohort, 2,035 patients had HF; 1,172 (58%) had HFpEF. One in-patient or two out-patient diagnosis codes of ICD-9 428.3X or ICD-10 I50.3X had 46% sensitivity, 88% specificity, 84% PPV, and 54% NPV. The addition of a BNP/NT-proBNP test code reduced sensitivity to 35% while increasing specificity to 91% (PPV = 84%, NPV = 51%). Broadening the diagnostic codes to ICD-9 428.0, 428.3X, and 428.9/ICD-10 I50.3X and I50.9 increased sensitivity at the expense of decreasing specificity (diagnostic code-only model: 87% sensitivity, 8% specificity, 56% PPV, 30% NPV; diagnostic code and BNP lab code model: 61% sensitivity, 43% specificity, 60% PPV, 45% NPV). In an analysis conducted to mimic real-world use of the computable phenotypes, any one in-patient or out-patient code of ICD-9 428/ICD-10 150 among the broader population (N = 3,755) resulted in lower PPV values compared with the Framingham cohort. However, one in-patient or two out-patient instances of ICD-9 428.0, 428.9, or 428.3X/ICD-10 150.3X or 150.9 brought the PPV values from the two cohorts closer together. While some misclassification remains, the computable phenotypes defined here may be used in claims databases to identify HFpEF patients and to gain a greater understanding of the characteristics of patients with HFpEF.

Advertising of OTC products in a Nigerian urban setting: content analysis for indications, targets, and advertising appeal.

OBJECTIVE: To identify the indications for which treatments were promoted, the segments of population targeted, and the type and extent of advertising appeal used for over-the-counter (OTC) products in a Nigerian urban setting. METHODS: Using a cross-sectional design, the content of advertisements for OTC products on radio, television, and billboards in a city in southwestern Nigeria were assessed during a 3-month period. Two coders independently assessed 1,492 advertisements for 49 brands of OTC products (interrater reliability [Cohen's kappa] = 0.83 [95% CI 0.80-0.90]). RESULTS: The most frequent indications for OTC products were aches and pain (42.9%), anemia/malnutrition (34.8%), and malaria (22.2%). Of advertisements, 92% were targeted at the primary end user. Use of appeal related to efficacy (100%), psychosocial enhancement (80%), and ease of use (40%) in visual, written, and audio messages was highest in ads on billboards. Efficacy appeal had the highest frequency across the three advertising media (100%); ease-of-use and safety appeal had the lowest frequency (40% and 7.4%, respectively). Nigerian movie stars were used as brand icons in advertisements of OTC products on radio (59.5%), television (52.9%), and billboards (49.6%). CONCLUSION: The majority of advertisements for OTC products in a Nigerian urban setting used advertising appeal related to efficacy and psychosocial enhancement. Promotional efforts by pharmaceutical manufacturers appear to focus on positive emotional appeal to influence drug purchase and use decisions.

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.

Real-world effectiveness of osteoporosis therapies for fracture reduction in post-menopausal women.

Studies examining real-world effectiveness of osteoporosis therapies are beset by limitations due to confounding by indication. By evaluating longitudinal changes in fracture incidence, we demonstrated that osteoporosis therapies are effective in reducing fracture risk in real-world practice settings. INTRODUCTION: Osteoporosis therapies have been shown to reduce incidence of vertebral and non-vertebral fractures in placebo-controlled randomized clinical trials. However, information on the real-world effectiveness of these therapies is limited. METHODS: We examined fracture risk reduction in older, post-menopausal women treated with osteoporosis therapies. Using Medicare claims, we identified 1,278,296 women age ≥ 65 years treated with zoledronic acid, oral bisphosphonates, denosumab, teriparatide, or raloxifene. Fracture incidence rates before and after treatment initiation were described to understand patients' fracture risk profile, and fracture reduction effectiveness of each therapy was evaluated as a longitudinal change in incidence rates. RESULTS: Fracture incidence rates increased during the period leading up to treatment initiation and were highest in the 3-month period most proximal to treatment initiation. Fracture incidence rates following treatment initiation were significantly lower than before treatment initiation. Compared with the 12-month pre-index period, there were reductions in clinical vertebral fractures for denosumab (45%; 95% confidence interval [CI] 39-51%), zoledronic acid (50%; 95% CI 47-52%), oral bisphosphonates (24%; 95% CI 22-26%), and teriparatide (72%; 95% CI 69-75%) during the subsequent 12 months. Relative to the first 3 months after initiation, clinical vertebral fractures were reduced for denosumab (51%; 95% CI 42-59%), zoledronic acid (25%; 95% CI 17-32%), oral bisphosphonates (23%; 95% CI 20-26%), and teriparatide (64%; 95% CI 58-69%) during the subsequent 12 months. CONCLUSION: In summary, reductions in fracture incidence over time were observed in cohorts of patients treated with osteoporosis therapies.

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.

Utilization of osteoporosis medication after a fragility fracture among elderly Medicare beneficiaries.

Osteoporosis medications are recommended for elderly patients after a fragility fracture. However, we found substantial under-treatment in the post-fracture year, especially among patients who had not previously received such medications. Improved treatment of elderly patients experiencing fragility fractures is needed. INTRODUCTION: Osteoporosis medications are recommended for elderly patients after a fragility fracture, but under-treatment is common. We determined osteoporosis medication use after fragility fractures and examined associated factors. METHODS: Our cohort included elderly (age ≥66 years) Medicare-enrolled patients who sustained fragility fractures January 1, 2008-December 31, 2011. Osteoporosis medication prescriptions were determined in the 12 months after the index fracture. Using multivariate logistic models, we examined the association between post-fracture osteoporosis medication use and predictors. RESULTS: Of 145,185 patients with fragility fractures (mean age 80.9 ± 7.8 years; 91.2 % white; 81.3 % female), 29.9 % sustained hip, 31.8 % vertebral, and 38.4 % non-hip-non-vertebral fractures. Overall, 30.4 % of the cohort received an osteoporosis medication in the 12-month post-fracture period. Of patients not receiving an osteoporosis medication in the pre-index period (n = 108,344), 14.9 % of all patients, 16.3 % of women, and 10.3 % of men received one in the post-fracture period. Corresponding values for patients receiving an osteoporosis medication in the pre-index period (n = 36,841) were 76.2, 76.5, and 72.2 %. Odds of post-fracture osteoporosis medication use were 68 % higher for women than for men. Osteoporosis diagnosis (odds ratio, 1.55; P < 0.0001) and bone-mineral-density tests before an index fracture (odds ratio, 1.24; P < 0.001) were associated with post-fracture osteoporosis medication use. CONCLUSIONS: Less than one third of our cohort received an osteoporosis medication in the post-fracture year, when risk of a second fragility fracture is highest. In those not already previously treated with an osteoporosis medication, only about 1 in 7 patients received treatment.