GRAND-4: the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab.

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.

Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis.

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.

GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated 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.

Assessing the cost-effectiveness of biologic agents for the management of moderate-to-severe rheumatoid arthritis in anti-TNF inadequate responders in Italy: a modelling approach.

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.

Medication-taking behaviour in Bulgarian women with postmenopausal osteoporosis treated with denosumab or monthly oral bisphosphonates.

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.

Hepatitis C virus infection and alanine transaminase levels in the general population: a survey in a southern Italian town.

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.

Persistencia en el tratamiento para la osteoporosis en pacientes posmenopáusicas en el ámbito de la Atención Primaria / Continuance of treatment for osteoporosis in postmenopausal patients in the Primary Care setting

Objetivo: Estimar la persistencia a los tratamientos para la osteoporosis posmenopáusica en el ámbito de Atención Primaria. Material y metodología: Estudio observacional, retrospectivo, realizado en seis centros de atención primaria. Criterios de inclusión: mujeres ≥ 50 años, diagnosticadas de osteoporosis que iniciaron tratamiento oral con bisfosfonatos, ranelato de estroncio o raloxifeno, entre enero de 2004 y junio de 2008. El objetivo principal fue estimar la persistencia global a un primer tratamiento para la osteoporosis posmenopáusica y la persistencia específica para cada tratamiento. En el análisis principal se consideró un cambio en el tratamiento como una interrupción y en el análisis secundario se permitió el cambio de tratamiento. Se consideraron tres cohortes de seguimiento: 1, 2 y 3 años. Los principales análisis estadísticos realizados fueron curvas de Kaplan-Meier, regresión logística y modelo de ANCOVA. Resultados: Se incluyeron 3.049 mujeres osteoporóticas. Grupos farmacológicos: 65% bisfosfonatos, 30% raloxifeno y 5% ralenato de estroncio. Edad media: 68 años; promedio del índice de Charlson: 0,4. En la cohorte 1 (N = 3.049) la persistencia global fue del 30%; en la cohorte 2 (N = 2.698) 35% y 16% a 1 y 2 años, respectivamente; en la cohorte 3 (N = 2.163) del 36%, 20% y 9% a 1,2 y 3 años, respectivamente (p < 0,01). La mediana de tiempo de persistencia para ácido alendrónico, risedrónico, raloxifeno y ralenato de estroncio fue de 149, 178, 210 y 89 días respectivamente (p < 0,001). Las variables asociadas a interrupción fueron: demencia, fracturas óseas y edad. Conclusiones: La persistencia en el tratamiento para la osteoporosis fue baja. Son necesarias nuevas estrategias para mejorar la persistencia de los tratamientos (AU)

Objective: To assess persistence to treatments for postmenopausal osteoporosis in primary care. Material and methodology: This retrospective, observational study was carried out in six Primary Care centers. Inclusion criteria: osteoporotic women 50 years or older, who initiated an oral treatment with bisphosphonates, raloxifene or strontium ranelate, between January 2004 and June 2008. The primary objective was to estimate persistence to treatment combining all treatments and by drug and regimen. In a primary analysis, switching treatments for postmenopausal osteoporosis was considered discontinuation, whereas in a secondary analysis, switching was allowed. Both analyses were performed on three follow-up-based cohorts according to data availability at 1, 2 and 3 years. Main statistical analyses performed were Kaplan-Meier curves, logistic regression and an ANCOVA model. Results: A total of 3,049 osteoporotic women were included. Pharmacological groups: 65% were treated with bisphosphonates, 30% with raloxifene and 5% with strontium ranelate. Mean age was 68 years; average Charlson co-morbidity index was 0.4. In cohort 1 (N = 3,049), persistence was 30%; in cohort 2 (N = 2,698), it was 35% and 16% at 1 and 2 years, respectively; in cohort 3 (N = 2,163), it was 36%, 20% and 9% at 1, 2 and 3 years, respectively (p < 0.01). Median duration of persistence to alendronic acid, risedronic acid, raloxifene and strontium ranelate was 149, 178, 210 and 89 days, respectively (p < 0.001). Variables associated with discontinuation were dementia, bone fractures and age (AU)