Fracture risk in women with osteoporosis initiated on gastro-resistant risedronate versus immediate release risedronate or alendronate: a claims data analysis in the USA.

The study results indicate that women with osteoporosis initiated on gastro-resistant risedronate have a lower risk of fracture than those initiated on immediate release risedronate or alendronate. A large proportion of women discontinued all oral bisphosphonate therapies within 1 year of treatment start. PURPOSE: Using a US claims database (2009-2019), we compared risk of fractures between women with osteoporosis initiated on gastro-resistant (GR) risedronate and those initiated on (a) immediate release (IR) risedronate or (b) immediate release alendronate. METHODS: Women aged ≥ 60 years with osteoporosis who had ≥ 2 oral bisphosphonate prescription fills were followed for ≥ 1 year after the first observed bisphosphonates dispensing (index date). Fracture risk was compared between the GR risedronate and IR risedronate/alendronate cohorts using adjusted incidence rate ratios (aIRRs), both overall and in subgroups with high fracture risk due to older age or comorbidity/medications. Site-specific fractures were identified based on diagnosis codes recorded on medical claims using a claims-based algorithm. Persistence on bisphosphonate therapy was evaluated for all groups. RESULTS: aIRRs generally indicated lower fracture risk for GR risedronate than IR risedronate and alendronate. When comparing GR risedronate to IR risedronate, statistically significant aIRRs (p < 0.05) were observed for pelvic fractures in the full cohorts (aIRRs = 0.37), for any fracture and pelvic fractures among women aged ≥ 65 years (aIRRs = 0.63 and 0.41), for any fracture and pelvic fractures among women aged ≥ 70 years (aIRRs = 0.69 and 0.24), and for pelvic fracture among high-risk women due to comorbidity/medications (aIRR = 0.34). When comparing GR risedronate to alendronate, statistically significant aIRRs were observed for pelvic fractures in the full cohorts (aIRR = 0.54), for any fracture and wrist/arm fractures among women aged ≥ 65 years (aIRRs = 0.73 and 0.63), and for any fracture, pelvic, and wrist/arm fractures among women aged ≥ 70 years (aIRRs = 0.72, 0.36, and 0.58). In all cohorts, ~ 40% completely discontinued oral bisphosphonates within 1 year. CONCLUSIONS: Discontinuation rates of oral bisphosphonate therapy were high. However, women initiated on GR risedronate had a significantly lower risk of fracture for several skeletal sites than women initiated on IR risedronate/alendronate, particularly those aged ≥ 70 years.

Fracture rates and economic outcomes in patients with osteoporosis prescribed risedronate gastro-resistant versus other oral bisphosphonates: a claims data analysis.

Patients with osteoporosis prescribed risedronate gastro-resistant had a lower incidence of fractures versus those prescribed other oral bisphosphonates. Administration of risedronate gastric-resistant does not require fasting, and this more convenient dosing administration may explain its improved efficacy. PURPOSE: Up to half of patients do not follow complex dosing instructions of immediate-release bisphosphonates used for the prevention of osteoporotic fractures, which can result in suboptimal effectiveness. Risedronate gastro-resistant (GR) offers a more convenient dosing option by eliminating the need for fasting. This study compares fracture rates and outcomes between osteoporosis women treated with risedronate GR (GR cohort) versus other oral bisphosphonates (other cohort). METHODS: Claims from women with osteoporosis in the USA were analyzed. Patients were classified into the two cohorts based on the first oral bisphosphonate observed (index date) and matched 1:1 based on patient characteristics. Patients were observed for ≥ 2 years following the index date. Fracture rates, health care resource utilization and costs, and treatment persistence were compared. RESULTS: In total, 2,726 patients were selected in each cohort (median age: 60.0 years). The incidence of fractures was lower in the GR versus the other cohort for any fracture sites (incidence rate ratio, 95% CI: 0.83, 0.70-0.97) and spine fractures (0.71, 0.54-0.95), although the respective rate of medication discontinuation at 2 years was 80.5% and 74.4%. Time to first fracture was delayed for the GR cohort, reaching statistical significance after 36 months. The GR cohort incurred fewer hospitalizations (incidence rate per 1,000 patient-years: GR = 106.74; other = 124.20, p < 0.05) translating into lower hospitalization costs per patient per year (GR = $3,611; other = $4,603, p < 0.05). CONCLUSIONS: Patients prescribed risedronate GR versus other bisphosphonates had a lower incidence of fractures, which may be explained by the fact that the GR formulation is absorbed even when taken with food.

Prevalence of type 2 inflammatory diseases in pediatric patients with atopic dermatitis: Real-world evidence.

BACKGROUND: Patients with atopic dermatitis (AD) are considered at increased risk of developing other type 2 inflammatory diseases. However, real-world evidence based on large commercially insured pediatric populations in the United States is scarce. OBJECTIVE: To use a large claims database (IBM MarketScan 2013-2017) in the United States to assess prevalence and incidence of type 2 inflammatory diseases in pediatric patients with AD. METHODS: Pediatric patients with AD were matched 1:1 to patients without AD. Prevalence was assessed for conjunctivitis, rhinitis, urticaria, asthma, eosinophilic esophagitis, and chronic rhinosinusitis/nasal polyps at the 12 months' post-index date (the first AD diagnosis date for patients with AD; a randomly selected outpatient visit for control patients). The incidence of other type 2 inflammatory diseases post-index was assessed among patients 0-2 years of age. RESULTS: A total of 244,776 AD and matched non-AD patients were selected. The prevalence and incidence of type 2 inflammatory diseases were higher among patients with AD. Overall, the prevalence more than doubled for asthma, eosinophilic esophagitis, urticaria, and rhinitis, and increased with AD severity. LIMITATIONS: AD identification was based on billing diagnoses; the observation period was only 12 months; and the study was limited to commercially insured patients. CONCLUSION: The burden of type 2 inflammatory diseases in pediatric patients with AD is substantial, highlighting the need to optimize management of AD and its numerous associated morbidities.

Treatment patterns of pediatric patients with atopic dermatitis: A claims data analysis.

BACKGROUND: Real-world evidence on treatment patterns of pediatric patients with atopic dermatitis (AD) is sparse. OBJECTIVE: To assess current treatment patterns in pediatric AD patients. METHODS: Retrospective observational analysis of commercial insurance and Medicaid administrative claims data (January 2011-December 2016) for pediatric AD patients, stratified by age and provider type. RESULTS: The analytic sample comprised 607,258 pediatric AD patients. Median observation period was 30.3 months. Overall, 78.6% were prescribed ≥1 AD medication; 86.7% were prescribed topical corticosteroids, and 5.4% were prescribed a calcineurin inhibitor. Systemic corticosteroids (SCSs) were prescribed for 24.4% of patients, 51.8% of whom did not have asthma or allergic comorbidities. Of the 46.6% prescribed an antihistamine and 16.2% prescribed montelukast, 62.0% and 41.3%, respectively, did not have asthma or allergic comorbidities. Systemic immunosuppressants were rarely prescribed (<0.5%). Higher potency topical corticosteroid and SCS use increased with age. Treatment patterns varied by provider type; specialists were more likely to prescribe higher potency topicals and/or systemics, regardless of patient age. A minority of patients were treated by or referred to a specialist. LIMITATIONS: Identification of AD patients relied on billing diagnoses; the disease severity was proxied by the treatment prescribed. CONCLUSION: Results indicate that SCSs, despite known risks, and other medications with disproven efficacy in AD are frequently prescribed, suggesting a need for safer and more effective alternatives.

Effects of variations in access to care for children with atopic dermatitis.

BACKGROUND: An estimated 50% of children in the US are Medicaid-insured. Some of these patients have poor health literacy and limited access to medications and specialty care. These factors affect treatment utilization for pediatric patients with atopic dermatitis (AD), the most common inflammatory skin disease in children. This study assesses and compares treatment patterns and healthcare resource utilization (HCRU) between large cohorts of Medicaid and commercially insured children with AD. METHODS: Pediatric patients with AD were identified from 2 large US healthcare claims databases (2011-2016). Included patients had continuous health plan eligibility for ≥6 months before and ≥12 months after the first AD diagnosis (index date). Patients with an autoimmune disease diagnosis within 6 months of the index date were excluded. Treatment patterns and all-cause and AD-related HCRU during the observation period were compared between commercially and Medicaid-insured children. RESULTS: A minority of children were evaluated by a dermatology or allergy/immunology specialist. Several significant differences were observed between commercially and Medicaid-insured children with AD. Disparities detected for Medicaid-insured children included: comparatively fewer received specialist care, emergency department and urgent care center utilization was higher, a greater proportion had asthma and non-atopic morbidities, high- potency topical corticosteroids and calcineurin inhibitors were less often prescribed, and prescriptions for antihistamines were more than three times higher, despite similar rates of comorbid asthma and allergies among antihistamine users. Treatment patterns also varied substantially across physician specialties. CONCLUSIONS: Results suggest barriers in accessing specialty care for all children with AD and significant differences in management between commercially and Medicaid-insured children. These disparities in treatment and access to specialty care may contribute to poor AD control, especially in Medicaid-insured patients.

Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication.

BACKGROUND: To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults. METHODS: This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT) post-echinocandin initiation. Adjusted incidence rate ratios (IRRs) were estimated for anidulafungin versus caspofungin and micafungin, overall and in patients with normal baseline LFT (Grade 0). RESULTS: Treatments included anidulafungin (n = 1700), caspofungin (n = 4431), or micafungin (n = 6547). The proportions with LFT Grade ≥ 3 pre-echinocandin initiation were: anidulafungin 40.4% versus caspofungin 25.9% (p <  0.001) and micafungin 25.6% (p <  0.001). Rates of severe underlying diseases or comorbidities were: critical care admissions: 75.3% versus 52.6 and 48.6%; and organ failures: 69.4% versus 46.7 and 51.5%. Adjusted IRRs of severe hepatotoxicity for anidulafungin versus caspofungin and micafungin were 1.43 (p = 0.002) and 1.19 (p = 0.183) overall, and 0.88 (P = 0.773) and 0.97 (P = 0.945) for normal baseline LFT, respectively. CONCLUSIONS: Accounting for confounders, severe hepatotoxicity risk was not significantly different across echinocandins in this real-world head-to-head study. Anidulafungin was used more frequently in patients with more comorbidities. Those with normal baseline LFT (least susceptible to confounding by indication), showed no elevated hepatotoxicity risk for anidulafungin.

Assessment of treatment patterns and healthcare costs associated with probable Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a chronic and severe form of epilepsy characterized by intractable seizures, cognitive impairment, and abnormal electroencephalogram findings with slow spike-wave complexes. It typically presents before age 8, but symptoms continue into adulthood and require lifelong treatment associated with significant clinical burden. Data on LGS-associated healthcare utilization and costs are limited. In this study we use a claims-based LGS classifier based on random forest methodology to identify patients with probable LGS from the a Medicaid multi-state database and assess its prevalence across the age spectrum, healthcare utilization, treatment patterns, costs, and comorbid conditions. The classifier identified patients with probable LGS across all ages, with up to 8% of 10-year-old patients with epilepsy identified as having probable LGS. The prevalence of probable LGS was lower in older age cohorts, indicating that it may be under-recognized in older patients. Our analysis showed that probable LGS is associated with considerably higher total healthcare and medical costs than non-LGS patients. The costs were generally consistent between age cohorts, suggesting that the cost burden extends beyond childhood and has a lifelong impact. Analysis of treatment patterns suggest that while the majority of probable LGS patients in this study received widest-spectrum AEDs, a considerable proportion did not and therefore may have been inadequately treated. Further, usage of clobazam and rufinamide was decreased in older compared to younger patient cohorts, indicating that older patient cohorts are less likely to be receiving optimum treatment for LGS. These findings indicate the need for increased clinical attention to LGS beyond pediatric years, with a focus on optimization of treatment for LGS patients of all ages with widest-spectrum AEDs. Timely recognition and adequate treatment of LGS are likely to result in improved outcomes and less costly management of this condition.

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.

Can social media data lead to earlier detection of drug-related adverse events?

PURPOSE: To compare the patient characteristics and the inter-temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor® ) and sibutramine (Meridia® ) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). METHODS: We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports. RESULTS: We analyzed 998 and 270 social media postings between 2001 and 2014, 69 003 and 7383 FAERS reports between 1997 and 2014 for atorvastatin and sibutramine, respectively. Social media reporters were younger (atorvastatin: 53.9 vs. 64.0 years, p < 0.001; sibutramine: 36.8 vs. 43.8 years, p < 0.001). Social media reviews contained fewer serious AEs (atorvastatin, pain: 2.5% vs. 38.2%; sibutramine, cardiovascular issues: 7.9% vs. 63.0%; p < 0.001 for both) and concentrated on fewer types of AEs (proportion comprising the top 20 AEs: atorvastatin, 88.7% vs. 55.4%; sibutramine, 86.3% vs. 65.4%) compared with FAERS. While social media sibutramine reviews mentioning cardiac issues helped predict those in FAERS 11 months later (p < 0.001), social media atorvastatin reviews did not help predict FAERS reports. CONCLUSIONS: Social media AE reporters were younger and focused on less-serious and fewer types of AEs than FAERS reporters. The potential for social media to provide earlier indications of AEs compared with FAERS is uncertain. Our findings highlight some of the promises and limitations of online social media versus conventional pharmacovigilance sources and the need for careful interpretation of the results. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Age-Related Emergency Department Reliance in Patients with Sickle Cell Disease.

BACKGROUND: Emergency Department Reliance (EDR: total emergency department [ED] visits/total ambulatory [outpatient + ED] visits) differentiates acute episodic ED users from those who may not have adequate access to outpatient care. OBJECTIVE: This study's aim was to investigate age-related patterns of EDR and associated health-care costs in pediatric patients with sickle cell disease (SCD) and those transitioning from pediatric to adult care. METHODS: State Medicaid data were used for this study. Patients with two or more SCD diagnoses and one or more blood transfusion were included. Quarterly rates of ED visits, EDR, SCD complications associated with ED visits, and ED visits resulting in hospitalization were evaluated. Risk factors associated with high EDR and the association between high EDR and health-care costs were explored through regression analyses. RESULTS: A total of 3208 patients were included. The most common SCD complications associated with ED visits were pain, infection, and pneumonia. Beginning at the age of 15 years, EDR rose from 0.17 to 0.29 visits per quarter at age 22 years, and remained high throughout adulthood. Regression analyses indicated that patients were most likely to have high EDR during the post-transition period and when experiencing an SCD complication. Patients with high EDR incurred statistically significantly higher inpatient and ED costs, resulting in significantly higher total health-care costs. CONCLUSIONS: Compared to children, patients transitioning to adulthood relied more on the ED for their care. In addition, patients with high EDR incurred more days in the hospital and significantly higher health-care costs, highlighting the need to improve transition-related support, including better access to primary care and increased engagement with patients with SCD.

Is addition of vasodilators to loop diuretics of value in the care of hospitalized acute heart failure patients? Real-world evidence from a retrospective analysis of a large United States hospital database.

BACKGROUND: Current guidelines recommend the use of intravenous (IV) vasodilators in addition to IV loop diuretics for the treatment of acute heart failure (AHF) patients without hypotension. The evidence basis for these recommendations is limited. METHODS AND RESULTS: Hospital billing records for 82,808 AHF patients in the United States were analyzed. Patients receiving IV loop diuretics alone were paired with patients receiving IV loop diuretics + IV nitrates or IV nesiritide with the use of propensity score matching, excluding those with hypotension and/or evidence of cardiogenic shock, myocardial infarction, or acute coronary syndrome. Compared with paired patients receiving IV loop diuretics alone, in-hospital mortality was similar among IV loop diuretics + IV nitrates patients (n = 4,401; 1.9% vs 2.0%; P = .88) and marginally higher for IV loop diuretics + IV nesiritide patients (n = 2,254; 2.2% vs 3.1%; P = .05). Compared with paired IV loop diuretics patients, IV loop diuretics + IV nitrates or IV nesiritide had longer lengths of stay (+1.6 and +2.1 days; P < .01) and 57% higher costs (P < .01). CONCLUSIONS: Among hospitalized AHF patients, the addition of IV vasodilators to IV loop diuretics did not lower inpatient mortality or rehospitalization rates compared with loop diuretics alone, and was associated with longer lengths of stay and higher hospitalization costs. Although the lack of complete clinical, socioeconomic, and post-discharge data may have confounded these results, this analysis questions whether currently available IV vasodilators can improve outcomes in hospitalized AHF patients.

Assessment of algorithms for identifying patients with triple-class refractory multiple myeloma using real-world data.

Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.

Age-related treatment patterns in sickle cell disease patients and the associated sickle cell complications and healthcare costs.

BACKGROUND: This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult patients with SCD. PROCEDURE: Data from Florida (1998-2009), New Jersey (1996-2009), Missouri (1997-2010), Kansas (2001-2009), and Iowa (1998-2010) state Medicaid were used. Patients with ≥2 SCD diagnoses and ≥1 transfusion event were included. Rates of transfusion events, SCD complications, and proportion of eligible patients receiving ICT were calculated. ICT eligibility was defined as receiving ≥10 transfusions over lifetime. SCD complications included pain, pulmonary event, infection event, renal, cardiovascular, stroke, leg ulcers, and avascular necrosis. Regressions were used to assess risk factors for transfusion and identify the main drivers of costs. RESULTS: The sample included 3,208 patients. The transfusion rate increased from 1-year-old to a peak at 16 years old, then dropped until age 26 and remained stable thereafter. In contrast the frequency of diagnoses for SCD complications increased markedly after age 16. Post-transition patients (≥18 years old) were significantly associated with fewer transfusions (odds ratio: 0.80, P = 0.002). Among eligible patients for ICT, there was no statistically significant difference in total cost between the ICT and no ICT groups (adjusted cost difference, $136, P = 0.114). CONCLUSIONS: Patients transitioning to adult care received less transfusions and hydroxyurea, less ICT when eligible for chelation therapy, had higher healthcare costs and suffered from more frequent SCD related complications than pediatric patients. These findings highlight the changes in treatment patterns corresponding to transition to adult care.

Epidemiologic Evaluation of Cardiovascular Risk in Patients Receiving Milnacipran, Venlafaxine, or Amitriptyline: Evidence from French Health Data.

BACKGROUND: Milnacipran, a selective serotonin and norepinephrine reuptake inhibitor, is approved by the Food and Drug Administration for the management of fibromyalgia. It has been available for many years in several countries outside the US for the treatment of depression. OBJECTIVE: To conduct population-based analyses comparing the risk of serious cardiovascular (CV) events (eg, acute myocardial infarction, stroke, congestive heart failure) associated with treatment with milnacipran compared with venlafaxine and amitriptyline, 2 other commonly prescribed drugs that also inhibit reuptake of norepinephrine and serotonin. METHODS: Information from the French Thales electronic health record database from 2001 to 2007 was used. Patients with 1 or more prescriptions for milnacipran, venlafaxine, or amitriptyline; 180 or more days of continuous eligibility prior to the first prescription; and no prior CV event diagnoses during the 180-day baseline period were included. A retrospective, matched-cohort design was employed. The incidence rates of CV events between cohorts receiving milnacipran, venlafaxine, and amitriptyline were compared using unadjusted incidence rate ratio (IRR) and adjusted conditional IRR based on Poisson regression. RESULTS: We identified 4452 milnacipran-venlafaxine and 3761 milnacipran-amitriptyline matched pairs. The matched cohorts had similar baseline characteristics. The unadjusted IRRs of any CV events, comparing milnacipran with venlafaxine or amitriptyline, were 1.02 (95% CI 0.73 to 1.44) and 1.30 (95% CI 0.90 to 1.89), respectively. Adjusted IRRs confirmed the statistical similarity in the CV event risk between milnacipran and venlafaxine (adjusted IRR = 1.29, 95% CI 0.76 to 2.17) or amitriptyline (adjusted IRR = 1.06, 95% CI 0.59 to 1.89). CONCLUSIONS: This French population-based study found that the risk of CV events was not significantly different for patients receiving milnacipran versus those receiving venlafaxine or amitriptyline.

Treatment patterns and sequencing in patients with rheumatic diseases: a retrospective claims data analysis.

OBJECTIVES: Long-term real-world management of inflammatory rheumatic diseases remains unclear, especially with the advent of new treatment options. This study characterizes the number of advanced treatments used by patients with selected rheumatic diseases (rheumatoid arthritis [RA], psoriatic arthritis [PsA], ankylosing spondylitis, juvenile idiopathic arthritis) and provides a contemporary portrait of treatment patterns and therapeutic sequencing among patients with RA and PsA. METHOD: Patients were selected from a large US claims database and classified into disease subsamples based on the latest rheumatic diagnosis recorded before/on the day of initiation of the first advanced treatment (index date). The total number of advanced treatments was assessed within the first 5 years following the index date. Treatment patterns and therapeutic sequencing were assessed over the first 2 years. RESULTS: Approximately 20% of patients received ≥2 distinct advanced treatments during the first year following index date - the proportion increased to almost 50% among patients with 5 years of observation. Most patients (RA: 76.8%; PsA: 88.7%) initiated a tumor necrosis factor as the first advanced treatment. Over the first 2 years after the index date, 1/3 of RA and PsA patients switched to another advanced treatment. More than 50% initiated a second treatment with the same mechanism of action (MOA). A small proportion of patients received a biosimilar. CONCLUSION: Despite advent of treatments with different MOA, cycling between treatments with the same MOA was common. Further studies with longer data follow-up would be needed to assess the impact of higher adoption of biosimilars on treatment patterns/sequencing.

Tolerability, efficacy, and safety of pegylated liposomal Doxorubicin in combination with Carboplatin versus gemcitabine-Carboplatin for the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review.

OBJECTIVE: To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine-carboplatin (Gem-Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature. METHODS: Using the PubMed database, a systematic review of peer-reviewed literature published between January 2000 and September 2009 was undertaken to identify studies related to the treatment of patients with PSROC with PLD-Carbo or Gem-Carbo. Studies reporting either response rate, progression-free survival (PFS), and/or overall survival (OS) were included. Treatment regimens, efficacy endpoints, and safety profiles were compared between the two combination therapies. RESULTS: Ten studies evaluating 608 patients (PLD-Carbo: 5 studies, 278 patients; Gem-Carbo: 5 studies, 330 patients) were identified. The mean planned doses were: PLD, 34.8 mg/m(2) and Gem, 993 mg/m(2). The dose intensity reported in Gem trials was lower (75% of the planned dose) than the dose intensity reported in PLD trials (93.7% of the planned dose), suggesting better tolerability for the PLD-Carbo regimen. Among patients receiving PLD-Carbo, 60.2% achieved a response (complete, 27.0%; partial, 33.2%), versus 51.4% of patients treated with Gem-Carbo (complete, 19.2%; partial, 32.2%). The median PFS times were 10.6 months and 8.9 months in the PLD-Carbo and the Gem-Carbo populations, respectively. The median OS was longer for the PLD-Carbo regimen (27.1 months) than for the Gem-Carbo regimen (19.7 months). The hematological safety profiles were comparable in the two groups, although grade III or IV anemia (PLD-Carbo, 13.6%; Gem-Carbo, 24.5%) and neutropenia (PLD-Carbo, 45.5%; Gem-Carbo, 62.9%) were more common in patients receiving Gem-Carbo. CONCLUSION: Results from this systematic analysis of peer-reviewed literature suggest that PLD-Carbo therapy is a rational alternative to Gem-Carbo for the treatment of patients with PSROC.

Risk of hepatotoxicity-related hospitalizations among patients treated with opioid/acetaminophen combination prescription pain medications.

OBJECTIVE: This study determined the risk of serious hepatotoxicity resulting in hospitalizations among patients prescribed opioid/acetaminophen combinations. METHODS: A retrospective cohort study using an insurance claims database was conducted. Adult patients with ≥1 claim for oxycodone/acetaminophen or hydrocodone/acetaminophen combinations were included (N = 1,228,356). A pre-post design was employed to compare serious hepatotoxicity risk before versus after initiation of opioid/acetaminophen combination. Serious hepatotoxicity risk between the opioid/acetaminophen group and a control group of opioid-alone users (N = 11,809) was also examined. Within the opioid/acetaminophen group, risk of hepatotoxicity-related hospitalizations pre- versus post-opioid/acetaminophen treatment was compared using the normal approximation with the binomial distribution. The incidence rate of hepatotoxicity-related hospitalizations for the opioid/acetaminophen group was compared with the opioid-alone group using multivariate Poisson regression adjusting for baseline differences between groups. RESULTS: Of the opioid/acetaminophen cohort, hepatotoxicity-related hospitalization risk in the 6-month post-opioid/acetaminophen period was lower than that in the pre-period with a risk reduction of 1.2 per 10,000 (pre-period = 0.12%; 95% confidence interval [CI], 0.12 to 0.13; post-period = 0.11%; 95% CI, 0.11 to 0.12). In the 12-month period, risk increased in the post-period by 2.4 per 10,000 (pre-period = 0.14%; 95% CI, 0.14 to 0.15; post-period = 0.17%; 95% CI, 0.16 to 0.18). After adjusting for confounders, the opioid-alone group did not demonstrate a lower rate of hepatotoxicity-related hospitalizations than the opioid/acetaminophen group (incidence rate ratio of opioid-alone over opioid/acetaminophen = 2.9; 95% CI, 1.8 to 4.7). CONCLUSIONS: There is no population data-based evidence supporting elevated risk of hepatotoxicity-related hospitalization associated with opioid/acetaminophen combinations.

Drug utilization and cost for erythropoiesis-stimulating agents in a long-term care resident population with chronic kidney disease.

OBJECTIVE: To compare drug-utilization patterns and costs in patients with chronic kidney disease (CKD), not on dialysis, yet receiving epoetin alfa (EPO) or darbepoetin alfa (DARB) in a long-term care setting. DESIGN: A retrospective analysis of pharmacy dispensing from January 2007 through March 2009, was conducted using the AnalytiCareSM LTC database. SETTING: Long-term care. PATIENTS, PARTICIPANTS: Patients>or=18 years of age, with >or=1 EPO or DARB dose dispensed, were included. Patients dispensed both agents, diagnosed with cancer, receiving chemotherapy, radiation therapy, or renal dialysis, were excluded. MAIN OUTCOME MEASURES: Mean cumulative erythropoiesis-stimulating agent (ESA) dose was used to calculate drug cost (using April 2009 wholesale acquisition cost) and dose ratio (Units EPO:mcg DARB). Results were also stratified by payer types. RESULTS: A total of 2,259 patients were identified (EPO 1,640; DARB 619). EPO patients were slightly older (76.1 vs. 74.8 years of age, P=0.021), with similar proportion of women, compared with DARB patients. Mean (SD) cumulative dose was 98,420 (122,381) Units for EPO and 360 (428) mcg for DARB, resulting in a dose ratio of 273:1 (Units EPO:mcg DARB). The corresponding drug cost was 42% higher with DARB than with EPO ($1,734 vs. $1,217, P<0.001). Stratified analysis by payer types yielded similar results (dose ratios: 299:1 and 270:1 [Units EPO:mcg DARB]); cost premiums: 30% and 44% for Medicare Part A/Facility and Medicare Part D/Medicaid groups, respectively. CONCLUSIONS: This study of long-term care CKD patients receiving ESAs reported 42% higher drug cost with DARB compared with EPO and a dose ratio of 273:1.

Prevalence of depression and anxiety in women newly diagnosed with vulvovaginal atrophy and dyspareunia.

OBJECTIVE: To quantify the association between vulvovaginal atrophy and depression, major depressive disorder, and anxiety. METHODS: Women with vulvovaginal atrophy from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (01/2010-09/2016) with ≥365 days of continuous insurance coverage before and after the first vulvovaginal atrophy/dyspareunia diagnosis (index date) were selected. Women with vulvovaginal atrophy were matched 1:3 to women without (controls) according to age, calendar year, health plan, and region. The study period spanned from 12 months before to 12 months after index date. The ratios of diagnosed depression, major depressive disorder, and anxiety among women with vulvovaginal atrophy and the controls were calculated. Logistic regressions adjusting for proxies of menopause were used to compare prevalence. RESULTS: In all, 125,889 women with vulvovaginal atrophy and 376,057 controls were included (mean age 60.7 [45-101]). The prevalence of depression, major depressive disorder, and anxiety was higher among women with vulvovaginal atrophy compared with controls (23.9% vs 18.9%, 6.3% vs 4.7%, 16.6% vs 11.3%), with prevalence ratios of 1.26, 1.33, and 1.47, respectively (all P < 0.0001). Highest prevalences and differences were observed in younger women. Findings were consistent when analyzing newly diagnosed conditions. When adjusting for proxies of menopause (insomnia, vasomotor symptoms, dysuria, and estrogen therapy), vulvovaginal atrophy remained significant (prevalence odds ratios; depression 1.23, major depressive disorder 1.22, anxiety 1.39; all P < 0.0001). CONCLUSIONS: Vulvovaginal atrophy is associated with a significantly higher prevalence/incidence of depression, major depressive disorder, and anxiety. The higher prevalence/incidence and greater differences in younger women highlight the need for a multidisciplinary approach and early diagnosis/management of vulvovaginal atrophy.