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Purpose: Geographic atrophy (GA), the advanced form of dry age-related macular degeneration, can result in irreversible blindness over time. We performed a systematic literature review to assess the humanistic and economic burden of GA., Methods: Predefined search terms were used to identify studies in PubMed, Embase, and Cochrane Library; conference abstracts also were searched., Results: Of 1111 unique studies identified, 25 studies on humanistic burden, 4 on economic burden, and 3 on both humanistic and economic burden of GA were included. Vision-related functioning and health-related quality of life (HRQOL) are poor in patients with GA. HRQOL is commonly measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25); patients with GA have significantly lower composite and subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision than individuals without GA. Driving is a particular concern, and inability to drive affects dependency. Vision-related quality of life (VRQOL) declines as GA progresses. While we identified only 7 reports describing the economic burden of GA, its direct costs may be substantial. In a US study, mean cost to the payer per patient with GA was $11,533 in the year after diagnosis. A multinational study estimated annualized total direct costs of €1772 per patient with GA, mainly driven by diagnostic tests and procedures (€1071). Patients with GA are at increased risk of falls and fractures, potentially increasing direct costs. Only one study evaluated indirect costs, estimating ~$24.4 billion in yearly lost wages among people with severe vision loss due to GA or drusen ≥125 μm., Conclusion: GA represents a significant humanistic burden. Evidence on the economic impact of GA is limited; characterizing the economic burden of GA requires further research. Interventions that reduce GA-related disability may improve HRQOL and reduce indirect costs., Competing Interests: SPS, WC, MI, and DLJ are employees of Apellis. AH, MB, and TT are employees of RTI Health Solutions. SW was an employee of RTI Health Solutions when this research was conducted. The author reports no other conflicts of interest in this work., (© 2021 Sarda et al.)

Purpose: Bisphosphonates and denosumab prevent bone complications in patients with bone metastases from solid tumours. This retrospective, longitudinal, cohort study provides data on their real-world use in this setting in Germany., Methods: Adults with bone metastases from breast, prostate or lung cancer who were newly initiated on a bisphosphonate or denosumab between 1 July 2011 and 31 December 2015 were identified from a German healthcare insurance claims database. Primary outcomes included persistence, compliance, discontinuation and switch rates at 12 months., Results: This study included 1130 patients with bone metastases: 555 (49%) had breast cancer, 361 (32%) prostate cancer and 242 (21%) lung cancer. Mean age was 65 years for patients with breast or lung cancer and 74 years for those with prostate cancer. Across all tumour types, compared with any bisphosphonate, 12-month persistence was higher with denosumab (breast cancer 78% vs 54-58%, prostate cancer 58% vs 50%, lung cancer 68% vs 34-60%), median time to discontinuation was longer with denosumab and switch rates were lower for denosumab (breast cancer 5% vs 14-19%, prostate cancer 2% vs 11%, lung cancer 3% vs 7-12%). Compliance at 12 months was longer for denosumab than for any bisphosphonate in breast cancer (75% vs 42-48%) and in prostate cancer (47% vs 36%)., Conclusions: Patients initiated on denosumab following a diagnosis of bone metastases from breast, prostate or lung cancer had greater medication persistence, longer time to discontinuation, improved compliance and lower switch rates than those initiated on a bisphosphonate.

Objectives: The first phase of the published OPAL-HK study was a single-group treatment phase, which showed that patiromer normalised serum potassium at 4weeks in patients with chronic kidney disease stages 3-4 who were receiving renin-angiotensin-aldosterone inhibitors. We utilised real-world data to provide a control comparison to evaluate patiromer's efficacy in lowering serum potassium., Materials and Methods: The Salford Kidney Study (SKS) in the United Kingdom provided a matched cohort. After applying OPAL-HK inclusion and exclusion criteria, patients with an outpatient potassium level between 5.1mmol/L to <6.5mmol/L and whose next outpatient level was checked 24-42 days later were selected. Patients underwent 1:1 matching with the 243 OPAL-HK patients using propensity matching based on 6 variables: age, gender, estimated glomerular filtration rate, diabetes, heart failure and potassium level. The study outcomes aligned with the OPAL-HK treatment phase: mean change in baseline potassium, and the proportion of patients with a potassium of 3.8 to <5.1mmol/L at follow-up., Results: The study comprised 87 precisely matched patients. The mean follow-up in the 87 SKS patients was 31±5 days. At baseline, matched patients had a mean potassium of 5.5±0.3mmol/L. At follow-up, the mean level was unchanged in SKS patients but was 4.5±0.5mmol/L in the OPAL-HK group (p<0.001), a mean (±SE) change of -1.00±0.06mmol/L. The target range of 3.8 to <5.1mmol/L was reached in 80% of OPAL-HK patients compared with 0% in the SKS cohort. There were very few interventions undertaken to reduce hyperkalaemia in SKS patients., Conclusions: Using real-world data as a matched control arm for the first phase of the OPAL-HK study, we highlight a potential role for patiromer in lowering potassium levels in patients with CKD 3-4 receiving renin-angiotensin-aldosterone inhibitors., Competing Interests: PK received research grants and speaker/consultancy fees from Vifor Fresenius Medical Care Renal Pharma outside the submitted work. GC is an employee and holds shares of the Vifor Pharma Group. MI was an employee of the Vifor Pharma Group from September 2018 to May 2020. Vifor Pharma markets patiromer. These declarations do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Bone complications (pathologic fracture, spinal cord compression, surgery to bone and radiation to bone) are a common problem in patients with multiple myeloma (MM). We set out to provide insights into the real-world burden of bone complications in patients with newly diagnosed MM (NDMM)., Methods: We conducted a retrospective review of medical charts of patients with NDMM whose disease had progressed following first-line treatment in the 3 months before data collection in 2016 in five European countries (France, Germany, Italy, Spain and the United Kingdom)., Results: The aggregated study population included 813 patients. Bone pain commonly led to MM diagnosis (63%) and 74% of all patients had two or more bone lesions at initiation of first-line treatment. Furthermore, 26% of patients experienced a new bone complication between MM diagnosis and disease progression following first-line treatment, despite 75% of individuals receiving bisphosphonates. Most bone complications (52%) occurred in the period before initiation of first-line treatment (mean duration: 2.3 months) and more than half of patients (56%) who experienced a new bone complication were hospitalised. Analgesics were used more frequently in patients with bone complications than in those without them (76% vs 50%, respectively). Furthermore, 51% of patients had renal impairment by the time first-line treatment was started. Overall, 25% of patients did not receive bisphosphonates for prevention of bone complications and one in four of those with renal impairment at initiation of first-line treatment did not receive bisphosphonates., Conclusions: Bone complications are common in patients with NDMM. They are frequently associated with hospitalization and analgesic use. Data from this study, conducted in the era of novel anti-myeloma therapies and before the approval of denosumab for use in patients with MM, suggest that although most patients (75%) received bisphosphonates, use of anti-resorptive therapy for prevention of bone complications may be suboptimal in patients with NDMM, irrespective of renal function.

Objectives: Within a median 1.2 years after patients have an initial diagnosis with multiple myeloma, up to 61% were diagnosed with renal impairment and 50% were diagnosed with chronic kidney disease. This study estimated economic burden associated with chronic kidney disease in multiple myeloma patients in the US., Methods: In this retrospective cohort study, patients ≥18 years old with ≥1 inpatient or ≥ 2 outpatient multiple myeloma diagnoses between 1 January 2008 and 31 March 2015 were identified from MarketScan® Commercial and Medicare Supplemental Databases. Chronic kidney disease patients had ≥1 diagnosis of chronic kidney disease Stages 1-5 (first chronic kidney disease diagnosis date = index date) on or after the first multiple myeloma diagnosis, and were propensity score matched 1:1 to multiple myeloma patients without chronic kidney disease, end-stage renal disease, dialysis, or other type of chronically impaired renal function. All patients had ≥six-month continuous enrollment prior to index date and were followed for ≥one month from index date until the earliest of inpatient death, end of continuous enrollment, or end of the study period (30 September 2015). The per-patient per-year healthcare resource utilization and costs were measured during follow-up. Costs were total reimbursed amount in 2016 US dollars., Results: A total of 2541 multiple myeloma patients with chronic kidney disease stages 1-5 and 2541 matched controls met the study criteria and were respectively 69.3 and 69.6 years, 54.5% and 55.3% men, and had 572.2 and 533.4 mean days of follow up. Compared to controls, chronic kidney disease patients had significantly (all P < 0.001) higher proportions (57.1% vs. 32.1%) and frequency (1.2 vs. 0.5) of inpatient admissions, frequency of emergency room visits (5.1 vs. 3.3), and total costs ($106,634 vs. $71,880). Sensitivity analyses found that patients with chronic kidney disease, end-stage renal disease, or dialysis had $78,455 ( P < 0.001) higher costs (per-patient per-year) than matched controls., Conclusions: The economic burden associated with chronic kidney disease in patients with multiple myeloma was estimated to be between $34,754 and $78,455 per-patient per-year. Given its substantial clinical and economic impact, preservation of renal function is important in multiple myeloma patient care.

Objectives: Skeletal-related events (SREs), i.e. pathologic fractures, spinal cord compression, surgery and radiation to bone, are serious skeletal complications that occur frequently in patients with bone metastases (BMs) from solid tumors (STs). Clinical guidelines recommend treatment with denosumab and intravenous bisphosphonates (IVBPs) to prevent SREs. However, therapy may be delayed by physicians due to perceived low risk of SREs or for other clinical reasons. This study estimated SRE incidence rates in treatment-naive (i.e. no denosumab or IVBPs) patients with BMs from STs in the US., Methods: In this retrospective cohort study adult patients with diagnoses of BM and ST between 1 January 2008 and 31 March 2015 were identified from MarketScan Databases. All patients had ≥6 months of data before the first BM diagnosis date (index date) and were followed for ≥6 months from the index date until the earliest of inpatient death, initiation of denosumab/IVBP therapy or end of data. The Kaplan-Meier curve was used to estimate cumulative incidence of SREs. The incremental healthcare cost of SREs was estimated and compared to propensity score matched non-SRE patients., Results: A total of 47,052 patients met the study criteria. Using the Kaplan-Meier method the cumulative incidences of SREs among treatment-naïve patients were 39.9% (95% confidence internal [CI]: 39.4-40.4), 46.3% (95% CI: 45.8-46.8), 52.5% (95% CI: 51.9-53.2) and 59.4% (95% CI: 58.6-60.3) by month 6, 12, 24 and 48 post index date, respectively. The SRE group was associated with higher all-cause total healthcare cost per-patient-per-year compared to those without SREs ($168,277 vs. $101,020, p < .001)., Conclusions: Almost half (46.3%) of the treatment-naïve population with BMs from STs experience SREs within 1 year of the first BM diagnosis. SREs were associated with an average $67,257 additional healthcare cost annually. Given the high SRE burden in these patients, early initiation of prophylactic therapy should be considered.

Aims: To estimate incremental healthcare resource utilization (HRU) and costs associated with skeletal-related events (SREs) secondary to multiple myeloma (MM), and HRU and cost differences in patients with one vs multiple SREs., Methods: Adults with MM diagnosis between January 1, 2010-December 31, 2014, with benefits coverage ≥12 months pre- and ≥6 months post-diagnosis were followed to last coverage date or December 31, 2015, excluding patients with prior anti-myeloma treatment or cancers. SREs were identified by diagnosis or procedure codes (pathological fracture, spinal cord compression, radiation, or surgery to the bone). SRE patients (index = first post-diagnosis SRE) were propensity score matched 1:1 to patients without SRE (assigned pseudo-index) using baseline characteristics, and ≥1 month of continuous enrollment after index/pseudo-index date was required. Per-patient-per year (PPPY) HRU and costs (2016 US$) were determined for inpatient, outpatient, emergency department (ED), and outpatient pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar's tests for proportions were used to assess differences. Negative binomial regression and generalized linear regression analyses estimated differences in HRU and costs, respectively, for the comparison of single vs multiple SREs., Results: Each cohort included 848 patients (mean age = 61 - 62 years, 57% male) with no significant differences in pre-index demographic or clinical characteristics between matched cohorts. Versus non-SRE patients, SRE patients had significantly higher PPPY use (p < .0001) of inpatient hospitalizations, ED visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs $108,160, p < .0001). Adjusted PPPY total costs were $209,820 in patients with multiple SREs; $159,797 in patients with one SRE., Limitations: SRE misclassification and residual confounding are possible., Conclusions: Among patients with MM, average annual costs were substantially higher in patients with SRE compared with matched non-SRE patients. The economic burden of SRE increased further with multiple events.

Objective: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives., Methods: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US$150,000. One-way deterministic and probabilistic sensitivity analyses were conducted., Results: From a societal perspective, compared with zoledronic acid, the use of denosumab resulted in an incremental cost of US$26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US$107,939 and a NMB of US$10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters., Limitations: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves., Conclusion: Denosumab's efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.

Objectives: Patients with multiple myeloma (MM) often experience debilitating skeletal-related events (SREs: pathologic fracture, radiation to bone [RB], surgery to bone [SB] or spinal cord compression [SCC]). This is the first comprehensive, prospective, observational analysis of healthcare resource utilisation (HRU), independently attributed to SREs by investigators, in patients with MM., Methods: Eligible patients had lytic bone lesions, life expectancy ≥6 months, Eastern Cooperative Oncology Group performance status ≤2 and ≥1 SRE in the 97 days before enrolment. Data were collected retrospectively for 97 days before enrolment and prospectively for 18-21 months., Results: Altogether, 153 patients were enrolled from Germany, Italy, Spain and the United Kingdom. Of the 281 observed SREs, 36.7% required inpatient stays (mean duration: 20.6 days per SRE [standard deviation (SD): 22.9]). SB and SCC were the SREs most likely to require stays (72.3% and 50.0% of SREs, respectively); SCC required the longest mean (SD) stay per event (40.5 [40.8] days). Overall, 179 SREs required outpatient visits; this was most likely for RB (74.8%) and least likely for non-vertebral fracture (50.0%)., Conclusions: All SREs were associated with substantial HRU; therefore, preventing SREs in MM will reduce the economic and resource burden on healthcare systems., (© 2018 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Persistence with osteoporosis therapy is critical for fracture risk reduction. This observational study evaluated medication-taking behaviour of women with postmenopausal osteoporosis receiving denosumab or oral ibandronate in real-world clinical practice in Bulgaria. Compared with ibandronate, densoumab was associated with a lower discontinuation rate and greater increases in bone mineral density., Purpose: Persistence with osteoporosis therapy is critical for fracture risk reduction and the effectiveness of such treatments may be reduced by low persistence. Alternative therapies such as denosumab may improve persistence. This study aimed to describe medication-taking behaviour in women with osteoporosis, prescribed denosumab or oral ibandronate, in Bulgarian clinical practice., Methods: This retrospective, observational, multicentre chart review (with up to 24 months follow-up) enrolled postmenopausal women initiating 6-monthly denosumab injection or monthly oral ibandronate treatment for osteoporosis between 1 October 2011 and 30 September 2012., Results: Overall, 441 women were enrolled (224 had initiated denosumab, 217 had initiated ibandronate). At baseline, more women in the denosumab group than in the ibandronate group had a previous fracture (25.5 vs 17.5%; p = 0.043) and past exposure to osteoporosis therapy (19.6 vs 12.0%; p = 0.028). At 24 months, 4.5% of women receiving denosumab had discontinued therapy compared with 56.2% of women receiving ibandronate. Median time to discontinuation was longer in the denosumab group (729 days; interquartile range (IQR), 728.3-729.0) than in the ibandronate group (367 days; IQR, 354.0-484.8; p < 0.001). At 24 months, there were significantly greater changes in BMD T-scores at the lumbar spine (p < 0.001) and femoral neck (p < 0.001) in patients receiving denosumab than in those receiving ibandronate. At 24 months, persistence with denosumab was 98.7%., Conclusion: This real-world study demonstrates there is a low discontinuation rate and high persistence with denosumab. Denosumab was associated with greater BMD increases than ibandronate, which could reduce fracture risk.

Using Swedish and Dutch registry data for women initiating bisphosphonates, we evaluated two methods of comparing the real-world effectiveness of osteoporosis treatments that attempt to adjust for differences in patient baseline characteristics. Each method has advantages and disadvantages; both are potential complements to clinical trial analyses., Purpose: We evaluated methods of comparing the real-world effectiveness of osteoporosis treatments that attempt to adjust for both observed and unobserved confounding., Methods: Swedish and Dutch registry data for women initiating zoledronate or oral bisphosphonates (OBPs; alendronate/risedronate) were used; the primary outcome was fracture. In adjusted direct comparisons (ADCs), regression and matching techniques were used to account for baseline differences in known risk factors for fracture (e.g., age, previous fracture, comorbidities). In an own-control analysis (OCA), for each treatment, fracture incidence in the first 90 days following treatment initiation (the baseline risk period) was compared with fracture incidence in the 1-year period starting 91 days after treatment initiation (the treatment exposure period)., Results: In total, 1196 and 149 women initiating zoledronate and 14,764 and 25,058 initiating OBPs were eligible in the Swedish and Dutch registries, respectively. Owing to the small Dutch zoledronate sample, only the Swedish data were used to compare fracture incidences between treatment groups. ADCs showed a numerically higher fracture incidence in the zoledronate than in the OBPs group (hazard ratio 1.09-1.21; not statistically significant, p > 0.05). For both treatment groups, OCA showed a higher fracture incidence in the baseline risk period than in the treatment exposure period, indicating a treatment effect. OCA showed a similar or greater effect in the zoledronate group compared with the OBPs group., Conclusions: ADC and OCA each possesses advantages and disadvantages. Combining both methods may provide an estimate of real-world treatment efficacy that could potentially complement clinical trial findings.

Renal impairment is a common complication of multiple myeloma and deterioration in renal function or renal failure may complicate clinical management. This retrospective study in patients with multiple myeloma using an electronic medical records database was designed to estimate the prevalence of renal impairment (single occurrence of estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m 2 on or after multiple myeloma diagnosis) and chronic kidney disease (at least two eGFR values <60 mL/min per 1.73 m 2 after multiple myeloma diagnosis that had been measured at least 90 days apart), and to describe the use of nephrotoxic agents. Eligible patients had a first diagnosis of multiple myeloma (ICD-9CM: 203.0x) between January 1, 2012 and March 31, 2015 with no prior diagnoses in the previous 6 months. Of 12,370 eligible patients, the prevalence of both renal impairment and chronic kidney disease during the follow-up period was high (61% and 50%, respectively), and developed rapidly following the diagnosis of multiple myeloma (6-month prevalence of 47% and 27%, respectively). Eighty percent of patients with renal impairment developed chronic kidney disease over the follow-up period, demonstrating a continuing course of declining kidney function after multiple myeloma diagnosis. Approximately 40% of patients with renal impairment or chronic kidney disease received nephrotoxic agents, the majority of which were bisphosphonates. As renal dysfunction may impact the clinical management of multiple myeloma and is associated with poor prognosis, the preservation of renal function is critical, warranting non-nephrotoxic alternatives where possible in managing this population., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Postmenopausal osteoporosis (PMO) is common among women over 50 years of age and is associated with an increased risk of fracture. Bone-targeted agents, such as denosumab, can reduce fracture risk in patients with PMO., Objective: The aim was to describe baseline characteristics and changes in bone mineral density (BMD) T-scores among women with PMO receiving denosumab in Bulgaria., Methods: This multicenter chart review included women with PMO receiving denosumab for ≥1 year in Bulgaria (October 2011-August 2013). Participants were required to have a baseline BMD T-score of ≤-2.5 standard deviations (SDs) at one or more skeletal sites., Results: Overall, 222 women were included. The mean (SD) age at denosumab initiation was 64.2 (8.5) years; 26.6% reported a previous osteoporotic fracture and 6.8% a previous hip fracture. Only half of those reporting a previous fracture (49.2%) had received prior osteoporosis therapy. At baseline, mean (SD) BMD T-scores were lumbar spine -3.2 SD (0.6 SD), total hip -2.3 SD (0.8 SD), and femoral neck -2.7 SD (0.7 SD). After 1 year of denosumab treatment, scores increased significantly at all three sites, reaching -2.7 SD (0.6 SD), -2.1 SD (0.9 SD), and -2.4 SD (0.7 SD), respectively (all p < 0.0001 vs. baseline). No serious adverse drug reactions were identified., Conclusion: Denosumab is usually prescribed in women with PMO at high fracture risk. In the patients who were persistent with treatment at 1 year, denosumab was well tolerated and effective at increasing BMD T-scores at several skeletal sites.

Unlabelled: This retrospective database study assessed 2-year persistence with bisphosphonates or denosumab in a large German cohort of women with a first-time prescription for osteoporosis treatment. Compared with intravenous or oral bisphosphonates, 2-year persistence was 1.5-2 times higher and risk of discontinuation was significantly lower (P < 0.0001) with denosumab., Introduction: Persistence with osteoporosis therapies is critical for fracture risk reduction. Detailed data on long-term persistence (≥2 years) with bisphosphonates and denosumab are sparse., Methods: From the German IMS® database, we included women aged 40 years or older with a first-time prescription for bisphosphonates or denosumab between July 2010 and August 2014; patients were followed up until December 2014. The main outcome was treatment discontinuation, with a 60-day permissible gap between filled prescriptions. Two-year persistence was estimated using Kaplan-Meier survival curves, with treatment discontinuation as the failure event. Denosumab was compared with intravenous (i.v.) and oral bisphosphonates separately. Cox proportional hazard ratios (HRs) for the 2-year risk of discontinuation were calculated, with adjustment for age, physician specialty, health insurance status, and previous medication use., Results: Two-year persistence with denosumab was significantly higher than with i.v. or oral bisphosphonates (39.8 % [n = 21,154] vs 20.9 % [i.v. ibandronate; n = 20,472] and 24.8 % [i.v. zoledronic acid; n = 3966] and 16.7-17.5 % [oral bisphosphonates; n = 114,401]; all P < 0.001). Patients receiving i.v. ibandronate, i.v. zoledronic acid, or oral bisphosphonates had a significantly increased risk of treatment discontinuation than did those receiving denosumab (HR = 1.65, 1.28, and 1.96-2.02, respectively; all P < 0.0001)., Conclusions: Two-year persistence with denosumab was 1.5-2 times higher than with i.v. or oral bisphosphonates, and risk of discontinuation was significantly lower with denosumab than with bisphosphonates. A more detailed understanding of factors affecting medication-taking behavior may improve persistence and thereby reduce rates of fracture., Competing Interests: Compliance with Ethical Standards Conflicts of interest This study was supported by Amgen GmbH. MS, MI, and TS are Amgen employees and shareholders. EP was an Amgen employee and shareholder at the time of conducting this study and manuscript preparation. PH has received honoraria, unrestricted educational grants, and research funding from Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Procter & Gamble, and Roche. IK has received honoraria, unrestricted educational grants, and funding from Amgen. LH has received honoraria, unrestricted educational grants, and research funding from Amgen, Eli Lilly, and Novartis. CN has received honoraria, unrestricted educational grants, and research funding from Amgen, Eli Lilly, Merck Sharp & Dohme, and UCB Pharma. PHK received honoraria, unrestricted grants, and research funding from Amgen, Eli Lilly, GlaxoSmithKline, Ipsen, Novo Nordisk, Novartis, Pfizer, Procter & Gamble, Roche, and Sanofi Aventis. HS has received honoraria and unrestricted educational grants from Prüfungseinrichtungen Baden-Württemberg, KV Baden-Württemberg, AOK, BEK, DAK, TKK, BKK’s, IKK, LKK, BK, Heilfürsorge, BG, Ärztekammer Baden-Württemberg, Patienten, Diverse Kliniken, Amgen, Anwerina, Astra, Daichi, Glaxo, Grünenthal, Janssen, Kade, Lilly, Medi, Medtronic, Omnia-Med, Orion, Medical Tribune, MSD, Mundipharma, Novartis, Nycomed, Pfizer, Procter & Gamble, Roche, Servier, and Teva. AAK has received honoraria, unrestricted educational grants, and research funding from Amgen, Baxter, Biomet, Boehringer Ingelheim, Dfine, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Procter & Gamble, and Roche. FT has received honorarium by Lilly, Amgen, Boehringer, and Takeda.

This study assessed persistence and compliance with anti-osteoporosis therapies, and associations between compliance and clinical outcomes (fracture, fracture-related hospitalization and death), in Hungarian women with postmenopausal osteoporosis. The study used the Hungarian National Health Insurance Fund Administration database and included women with PMO aged at least 50 years, for whom a prescription for anti-osteoporosis medication had been filled between 1 January 2004 and 31 December 2013 (index event). Persistence (prescription refilled within 8 weeks of the end of the previous supply) was evaluated over 2 years; good compliance (medication possession ratio ≥ 80 %) was evaluated at 1 year. Associations between compliance and clinical outcomes (data collected for up to 6 years) were assessed with adjustment for baseline covariates. A total of 296,300 women met the inclusion criteria (524,798 index events). Persistence and compliance were higher for less frequent and parenteral therapies (1- and 2-year persistence: half-yearly [parenteral] vs. daily/weekly/monthly [oral and parenteral], 81 and 38 % vs. 21-34 and 10-18 %, respectively; parenteral vs. oral, 75 and 36 % vs. 32 and 16 %; good compliance: half-yearly vs. daily/weekly/monthly, 70 vs. 24-39 %; parenteral vs. oral 78 vs. 36 %). Good compliance significantly reduced the risks of fracture, fracture-related hospitalization and death (relative risk vs. non-compliance [95 % confidence interval]: 0.77 [0.70-0.84], 0.72 [0.62-0.85] and 0.57 [0.51-0.64], respectively; P < 0.01). Improving compliance through long-interval parenteral therapies may result in clinical benefits for patients.

Unlabelled: The objectives of this study were to estimate persistence with denosumab and put these results in context by conducting a review of persistence with oral bisphosphonates. Persistence with denosumab was found to be higher than with oral bisphosphonates., Purpose: This study had two objectives: to analyse persistence in Swedish women initiating denosumab for treatment of postmenopausal osteoporosis (PMO) and to put these findings in context by conducting a literature review and meta-analysis of persistence data for oral bisphosphonates., Methods: The study used the Swedish Prescribed Drug Register and included women aged at least 50 years initiating denosumab between May 2010 and July 2012. One injection of denosumab was defined as 6-month persistence. Women were considered persistent for another 6 months if they filled their next prescription within 6 months + 56 days and survival analysis applied to the data. A literature search was conducted in PubMed to identify retrospective studies of persistence with oral bisphosphonates and pooled persistence estimates were calculated using a random-effects model., Results: The study identified 2,315 women who were incident denosumab users. Mean age was 74 years and 61% had been previously treated for PMO. At 12 and 24 months, persistence with denosumab was 83% (95% CI, 81-84%) and 62% (95% CI, 60-65%), respectively. The literature search identified 40 articles for inclusion in the meta-analysis. At 12 and 24 months, persistence with oral bisphosphonates ranged from 10% to 78% and from 16% to 46%, with pooled estimates of 45% and 30%, respectively., Conclusion: These data from the Swedish Prescribed Drug Register and literature review suggest that persistence was higher with denosumab than with oral bisphosphonates.

Unlabelled: This database analysis of over 4,000 German women prescribed oral bisphosphonates between December 2004 and November 2007 showed that compliance and persistence with oral bisphosphonates in German women with osteoporosis were inadequate., Introduction: GRAND is a database analysis designed to investigate persistence and compliance with oral bisphosphonate regimens, and their association with fracture incidence, in women with osteoporosis., Methods: Diagnostic, treatment and fracture data were obtained from the IMS Disease Analyzer patient database in Germany. Women with osteoporosis prescribed one of six specified oral bisphosphonates between December 2004 and November 2007 with no similar prescription for at least 1 year beforehand were eligible for analysis. Those treated with intravenous bisphosphonates were excluded. Persistence (prescription refill gap of ≤ 30 days or change of treatment frequency) and compliance (medication possession ratio) were measured for 2 years from therapy start., Results: Data from 4,147 women were evaluable, with a median oral bisphosphonate treatment duration of 145.5 days. Persistence rates after 1 and 2 years were 27.9% and 12.9%, respectively, and 66.3% of women were compliant. As expected, persistence rates were higher when the refill gap was increased to 60 or 90 days. No significant differences in 1-year persistence between patients on weekly or monthly treatment regimens were observed (28.6% and 29.4%, respectively), although 1-year persistence with daily treatment was only 7.2%. After 24 months of therapy, compliant women had fewer fractures than non-compliant women (88.1% and 85.0% fracture-free, respectively; p = 0.0147). In multivariate Cox regression analysis, treatment compliance was the only factor that significantly decreased fracture risk (p = 0.0034)., Conclusions: Compliance and persistence with oral bisphosphonates in German women with osteoporosis were inadequate. Better compliance and persistence can prevent fractures in these women.

Objectives: The objective of this study is to assess cost-effectiveness of different biologic strategies in patients with moderate-to-severe active RA after an insufficient response to anti-TNF agents within the context of the Italian healthcare system., Methods: Simulation models were developed allowing for potential biologic therapy switch at each 6-month time point in case of an insufficient response to the previous biologic agent. Biologic treatments included etanercept, abatacept, adalimumab, rituximab or infliximab. Effectiveness criteria for these models were defined as achieving a state of low disease activity (LDAS) [DAS28 ≤3.2] or remission (RS) [DAS28<2.6]. Monte-Carlo simulations were performed for each sequence to manage data variability., Results: The biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appeared significantly more efficacious over 2 years (102 days in LDAS) compared to rituximab (82 days in LDAS). The sequence using abatacept after 2 anti-TNF agents appeared significantly more efficacious (63 days in LDAS) compared to using a third anti-TNF agent (32 days in LDAS). Mean cost-effectiveness ratios showed significantly lower costs per day in LDAS with abatacept used after one anti-TNF agent (€376) compared to rituximab (€456). The sequence using abatacept after 2 anti-TNF agents was also more cost-effective (€642 per day in LDAS) versus a sequential use of anti-TNF therapies (€1164 per day in LDAS). All comparisons were confirmed when using the remission effectiveness criteria., Conclusions: The results of this health economics modelling study suggest that the biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appears significantly more effective and cost-effective versus a similar sequence using rituximab for achieving remission or LDAS. The results also indicate that in the case of an insufficient reponse to 2 anti-TNF agents, abatacept appears more effective and cost-effective than using a 3rd anti-TNF agent.

Background: The health-related quality of life (HRQL) is an important indicator of the burden of musculoskeletal disease. The Medical Outcome Study Short-Term 36 (SF-36) is the most used tool that evaluates HRQL as a subjective perception about psychological and physical limitations due to an underlying illness. The purpose of this study was to compare the HRQL scores among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) and a selected sample of health people and determine their relationship with measures of clinical condition., Methods: 799 patients (469 with RA, 164 with AS, 65 with axial PsA and 101 with peripheral PsA) accepted the invitation to participate. 1579 healthy controls were used for the comparison. We calculated scores for the eight SF-36 subscales, the Physical Component Summary (PCS) score, and the Mental Component Summary (MCS) score, according to published algorithms. Disease-related characteristics included disease duration, comorbidity, a measure for disease activity and for radiographic damage. The presence of comorbidity was ascertained through patient's self-reports by the Self-Administered Comorbidity Questionnaire (SCQ). Comparison were performed with respect to sex and age, and s-scores were calculated for comparison with the norm. Multivariate analyses were used to assess the relationship between HRQL and radiographic damage, disease activity, and socio-demographic data., Results: The four inflammatory rheumatic diseases (IRD), compared to controls, significantly impaired all eight health concepts of the SF-36 (p < 0.0001) in both component PCS and MCS scores (p < 0.0001). Overall, the dimensions typically affected were physical functioning, limitations due to physical function, and bodily pain. The disease with the worst HRQL for those dimensions was RA. The multivariate analyses revealed that the physical component was influenced by a high disease activity and comorbidity. The severity of psoriatic lesions was associated with poor mental functioning in patients with PsA., Conclusion: Chronic IRD have a clearly detrimental effect on the HRQL in both sex and in age groups, and physical domain is more impaired than mental and social ones.

Background/aim: The aim of the study was to estimate the prevalence, risk factors and genotype distribution of hepatitis C virus (HCV) in the general population older than 5 years of age in a southern Italian town. The positive predictive value of alanine transaminase (ALT) screening in identifying HCV positive subjects was also assessed., Methods: Cluster random sampling from the census of the general population was used. ELISA and RIBA tests assessed the presence of anti-HCV; nested reverse transcription polymerase chain reaction (RT-PCR) was used to identify HCV-RNA; genotyping was performed by INNO-LIPA III. The association linking anti-HCV seropositivity with potential risk factors was assessed by multiple logistic regression analysis., Results: Among the 488 subjects enrolled, 79 (16.2%) were anti-HCV positive. The prevalence increased from 1.2% in subjects 6-29 years of age to 42.1% in those > or = 60 years. Forty percent of these positive subjects also had abnormal ALT level and 54.4% were HCV RNA positive by PCR. The positive predictive value of the ALT test in identifying anti-HCV positive subjects was 65%; however, it was 46.7% in subjects younger than 60 years of age and 90.5% in those 60 or older. Genotype 1b was detected in 74% of subjects, type 2c in 23.3%, and type 1a in 2.3%. The only two variables significantly associated with HCV seropositivity in multivariate analysis were age older than 45 years (O.R. 8.5; CI 95%=3.0-24.1) and past use of glass syringes (O.R. 3.4; CI 95%=1.5-7.6)., Conclusions: These findings confirm that HCV infection is endemic in southern Italy, particularly among the elderly. Percutaneous exposure, such as injections with nondisposable, multiple-use, glass syringes used in the past for medical purposes may have played a major role in the spread of HCV infection. ALT screening is not useful in detecting HCV positive subjects in the general population, particularly among subjects who could benefit from antiviral therapy.