Rmc Herings

Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study

ABSTRACT Objective: This study aimed to investigate the association between persistent use of bisphosphonates and the risk of osteoporotic fractures in clinical practice. Methods: Data were obtained from the PHARMO Record Linkage System, which includes, among other databases, drug-dispensing records from community pharmacies linked to hospital discharge records of more than two million subjects in defined areas in the Netherlands. Persistence with bisphosphonate therapy was assessed during a period of 3 years. A nested matched case control study (cases:controls = 1:10) was performed to study the association between persistent bisphosphonate use and hospitalisation for osteoporotic fractures and analysed by conditional logistic regression analysis. The analyses were adjusted for patient characteristics such as previous hospitalisations for fractures, co-morbidity and co-medication. Results: 14 760 new female users of bisphosphonates were identified of which 541 women had a hospitalisation for osteoporotic fracture after start of bisphosphonate treatment (1–3 years follow-up). One-year persistence rates increased from 33% with alendronate daily to 48% with alendronate weekly, an increase of 15%. Similar results were obtained with risedronate daily and weekly. One year persistent use of bisphosphonates resulted in a statistical significant 26% lower fracture rate (OR 0.74; 95%CI 0.57–0.95) whereas 2 year persistent use resulted in a 32% lower rate (OR 0.68; 95%CI 0.47–0.96). Conclusions: Persistent use of bisphosphonates decreases the risk of osteoporotic fractures in clinical practice. Approximately 6% of fractures among users of bisphosphonates could be prevented if persistence was improved by 20%. However, current persistence with bisphosphonate therapy is suboptimal and strategies that further increase persistence are likely to further prevent the number of fractures.

Cardiovascular comorbidities among patients with metastatic colorectal cancer

Abstract Aim: As comorbidities may impact treatment decisions, prognoses and quality of care, this study determined the rate of comorbid cardiovascular diseases in patients with metastatic colorectal cancer

PCN19 BREAST CANCER PATIENTS ARE TWICE AS LIKE TO DEVELOP ARTERIAL THROMBOEMBOLIC EVENTS AFTER DIAGNOSIS COMPARED TO CANCER-FREE WOMEN

PCN14 SYSTEMATIC REVIEW OF EFFICACY OUTCOMES REPORTED IN RANDOMISED CONTROLLED TRIALS OF FIRST-LINE (1L) THERAPIES FOR METASTATIC BREAST CANCER (MBC) Harper C, McCormick AL, Sabaté E Complete Medical Group, Glasgow, UK, Complete Medical Group, Macclesfield, UK, F. Hoffmann—La Roche Ltd, Basel, Switzerland OBJECTIVES: There is currently some debate around the optimal role of overall survival (OS) as a gold standard in assessing the benefits of oncology products. The objective of this analysis was to provide evidence to inform this discussion from a review of the clinical outcomes in 1L mBC trials reported over the last 10 years. METHODS: MEDLINE and Cochrane databases were searched to identify randomised controlled trials of treatments for 1L mBC published between January 1998 and February 2009. Studies in exclusively human epidermal growth factor receptor 2-positive populations were excluded. RESULTS: Clinical efficacy data were extracted from 36 trials. All 36 trials reported response rate (RR), 34 reported a progressionbased end point and 33 reported OS. The most commonly stated primary efficacy end points were progression-based; only 6 trials stated OS as the primary end point. Improvement in median OS ranged from 0.1 to 7.8 months, improvement in median progression-free survival (PFS) ranged from 0.1 to 6.4 months and improvement in RR ranged from 0.3% to 28%. Fourteen trials (39%) reported a significant progression-based benefit, 4 of which (36%) reported significant median OS. Each of these 4 trials also reported a significant benefit in RR and median PFS. CONCLUSIONS: Overall, very few 1L mBC trials have reported a significant median OS benefit. Where a significant OS benefit was reported, a significant overall RR and PFS benefit was also reported. These findings appear important in light of the ongoing debate on the relevance of currently used clinical end points in mBC trials.

PCV1 THE ROLE OF LDL-LEVELS IN INITIATING STATIN TREATMENT

PCV1 THE ROLE OF LDL-LEVELS IN INITIATING STATIN TREATMENT van der Bij S, Heintjes E, Plat A, Sturkenboom MC, Penning-van Beest FJ, Herings RMC PHARMO Institute, Utrecht,The Netherlands, Erasmus University Medical Center, Rotterdam,The Netherlands OBJECTIVES: To assess the proportion of patients initiated on statin treatment among patients of various cardiovascular risk groups and the probability of statin treatment given certain LDLlevels in daily practice. METHODS: From the PHARMOdatabase, we selected patients who had an LDL-measurement in 2006 and no statin use in the year before. Per category of LDLlevels, i.e. 2.5, 2.6–4.0, 4.1–5.0 and >5.0 mmol/l, we determined the proportion of patients treated within 6 months after the measurement among those with cardiovascular disease (CVD, group I), with diabetes type 2 and no CVD (DM2, group II), and without CVD or DM2 (group III). The association between LDL-levels and statin treatment was determined using logistic regression adjusting for age, gender, CVD and DM2. RESULTS: Group I included 14,267 patients, group II 9,224 patients, and group III 54,102 patients. Overall, the proportions of patients receiving statins within 6 months after LDLmeasurement were 19% for group I and II and 8% for group III. These proportions ranged from 8%, 6% and 2% for patients with baseline LDL-levels 2.5 mmol/l, to 49%, 43% and 32% in patients with LDL-levels >5.0 mmol/l. Multivariate modelling showed that compared to patients with LDL 2.5 mmol/l (reference) the relative probability of statin treatment increased with LDL-levels: RR 2.6 (2.4–2.9) for 2.6–4.0 mmol/l, RR 5.8 (5.3–6.3) for 4.1–5.0 mmol/l, and RR 11.9 (10.9–13.1) for >5.0 mmol/l. Patients with CVD (RR 2.0 (1.9–2.1)) or DM2 (RR 2.5 (2.4–2.7)) were more likely to receive statin treatment. CONCLUSIONS: This study shows that, as expected, among statinnaïve patients the probability of statin treatment following LDL measurement increased with higher LDL-levels and pre-existing morbidity. However, the potential to further improve health outcomes exists because, even among patients with known CVD or DM2, approximately 55% of patients with LDL levels >5.0 mmol/l did not receive statin treatment.

PCV5 NON-PERSISTENT USE OF ANTIHYPERTENSIVE DRUGS INCREASES RISK OF HOSPITALIZATIONS FOR STROKE BY NEARLY 20%

PCV5 NON-PERSISTENT USE OF ANTIHYPERTENSIVE DRUGS INCREASES RISK OF HOSPITALIZATIONS FOR STROKE BY NEARLY 20% Breekveldt-Postma NS, Siiskonen SJ, Penning-van Beest FJA, Erkens JA,Vincze G, Falvey H, Herings RMC PHARMO Institute, Utrecht,The Netherlands, Novartis Pharma AG, Basel, Switzerland OBJECTIVES: Low persistence with antihypertensive drug treatment (AHT) is expected to limit patient’s benefits in terms of a reduction of cardiovascular and cerebrovascular disease. This study investigated the relationship between persistence with antihypertensive drugs and the risk of stroke in clinical practice. METHODS: From the PHARMO Record Linkage System comprising, among others, linked drug-dispensing and hospital records of >2 million inhabitants in The Netherlands, new users of AHT were identified in the period 1993–2002. Persistence with AHT was determined by summing the number of days of continuous treatment (gaps between dispensings of <60 days). Patients were classified as persistent if they remained on AHT for at least two years. The outcome of interest was the first hospital admission for stroke occurring two or more years after initiation of AHT therapy. Patients were classified as high, intermediate or low cardiovascular risk based on other cardiovascular drug use and hospitalizations during the first two years of follow-up. RESULTS: The study included 98,485 patients of whom 16% were at high cardiovascular risk. About 50% (n = 48,548) of all patients were persistent with AHT for two years, and 2.1% (n = 2093) were hospitalized for stroke in the period of two or more years after initiation of AHT therapy. Multivariate analyses showed that non-persistent users of AHT had a 16%–19% increased risk for stroke compared to persistent users (Low/intermediate risk group RRadj = 1.19; 95% CI: 1.07–1.32; high risk group RRadj = 1.16; 95% CI: 0.97–1.39). CONCLUSION: In clinical practice antihypertensive drug treatment is used over too short a time interval to have maximum benefit from preventing stroke.

PDB69 DETERMINANTS OF STOPPING TREATMENT WITH ORAL ANTIDIABETIC DRUGS IN DAILY CLINICAL PRACTICE

DETERMINANTS OF STOPPINGTREATMENTWITH ORAL ANTIDIABETIC DRUGS IN DAILY CLINICAL PRACTICE Koerselman J, van der Bij S, Erkens JA, Kessabi S, Groot MT, Penning-van Beest FJA, Herings RMC PHARMO Institute, Utrecht, Utrecht,The Netherlands, Novartis Pharma AG, Basel, Switzerland, Novartis Pharma B.V, Arnhem,The Netherlands OBJECTIVES: In daily practice many Type 2 Diabetes Mellitus (T2DM-)patients discontinue treatment. Therefore, the aim of this study was to investigate the determinants of (non-) persistence with oral antidiabetic drugs (OADs) in daily clinical practice. METHODS: From the PHARMO record linkage system, comprising among others linked drug-dispensing, and hospital data for >2.3 million subjects in The Netherlands, new users of OADs were identified in the period 1999–2005. Patients with 1 year of follow-up, were included in the study-cohort. Persistence with OAD-treatment in the first year of therapy was determined using the method of Catalan. Potential determinants of (non-)persistence included patient-characteristics, type of initial OAD-therapy, and cardiovascular co-morbidity. RESULTS: The study included 33,299 new users of OADs. One year after start, 42% of new T2DM-patients had stopped using any OAD. The risk of non-persistence was decreased with male gender (HR: 0.97; 95% CI: 0.94–1.00), and cardiovascular drug use (HR: 0.91; 95% CI: 0.86–0.97). Regarding age, compared to patients 76 years, the age-group 55–75 years had a 16% lower risk, and the age-group 30–44 years had a 32% increased risk of non-persistence. Patients starting on combined metformin + SU had a lower risk of non-persistence with any OAD; compared to patients starting on metformin monotherapy, the risk was 23% lower (HR: 0.77; 95% CI: 0.70–0.85). The risk of nonpersistence was increased with a specialist as first prescriber (HR: 1.20; 95% CI: 1.15–1.26), higher initial daily dose (HR: 1.09; 95% CI: 1.00–1.22), and higher initial daily dosing frequency (HR: 1.10; 95% CI: 1.02–1.20). CONCLUSION: In daily clinical practice about 40% of new T2DM-patients stop OADtherapy within one year. Determinants of stopping OADmedication were male gender, age-group, specialist as first prescriber, dosing, cardiovascular drug-use, and type of initial OAD-treatment.

PGI22 BURDEN OF ILLNESS IS HIGHEST IN PATIENTS WITH SEVERE PAIN SYMPTOMS

PGI22 BURDEN OF ILLNESS IS HIGHEST IN PATIENTS WITH SEVERE PAIN SYMPTOMS Ten Berg MJ, Goettsch WG, Siiskonen SJ,Van den Boom G, Smout AJPM, Herings RMC PHARMO Institute for Drug Outcomes Research, Utrecht,The Netherlands; Novartis Pharma B.V, Arnhem,The Netherlands; University Medical Centre Utrecht, Utrecht,The Netherlands BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder. Previous studies have shown that the burden of illness of IBS is high. It has been suggested that the quality of life and medical costs of IBS patients are associated with the severity of pain. This study aimed to quantify the burden of illness of IBS in relation to the severity of IBS symptoms. METHODS: Patients identified at community pharmacies as mebeverine users were administered a questionnaire regarding 1) the Rome II criteria for IBS, 2) predominant type of stool during symptomatic episodes, 3) severity of symptoms (abdominal pain and discomfort), 4) generic (SF-36) and disease-specific quality of life (IBS-QOL), 5) current health status (utilities, EQ-5D and SF6D), and 6) loss of productivity. Associations between severity of symptoms and burden of illness (including SF-36, IBS-QOL, EQ-5D, SF6D, direct medical cost and loss of productivity) were assessed. RESULTS: For 168 patients, who met the Rome II criteria for IBS, information on severity of symptoms was available. The majority of patients (98, 58%) were categorized as having severe symptoms of IBS. 47 (28%) patients were suffering from moderate symptoms and 23 (14%) patients had mild symptoms or were asymptomatic. All components of SF-36 scored lower as the symptom severity increased. The IBS-QOL score was lower (71.4, 95%CI: 67.5–75.3) for patients with severe symptoms than for patients with moderate IBS and mild/asymptomatic IBS (81.8, 95%CI: 78.6–85.0 vs. 81.3, 95%CI: 75.5–87.1). The EQ-5D score was also lower (58.3, CI95% 59.5–65.3) for patients with severe symptoms compared to the two other groups (68.8 and 66.3). CONCLUSIONS: This study clearly indicates that the burden of illness of patients with IBS increases with increasing severity of symptoms.

PGI12 HEALTH-RELATED QUALITY OF LIFE AND PATIENT SELFPERCEIVED HEALTH STATUS IN IBS

PGI12 HEALTH-RELATED QUALITY OF LIFE AND PATIENT SELFPERCEIVED HEALTH STATUS IN IBS Ten Berg MJ, Goettsch WG,Van den Boom G, Smout AJPM, Herings RMC PHARMO Institute, Utrecht, Netherlands; Novartis Pharma B.V, Arnhem, Netherlands; University Medical Centre, Utrecht, Netherlands OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic and episodic disorder characterized by abdominal pain and altered bowel habits. Its impact on generic and disease-specific quality of life and self-perceived health status is rarely assessed in The Netherlands. This study assessed the impact of IBS on healthrelated quality of life (HRQoL). METHODS: Patients using mebeverine, identified at community pharmacies, were administered a questionnaire regarding ROME-II-criteria to confirm the IBS diagnosis, abdominal complaints, use of medical resources, abdominal pain and discomfort (IGA-P VAS with 0 = no pain and 1 = very severe pain), patient self-perceived health status (VAS with 0 = worst imaginable health state i.e. death and 1 = best possible health state, and SF-6D), generic HRQoL (SF-36) and IBS-specific HRQol (IBSQoL). SF-36 outcomes were compared to a random sample of the Dutch population and other Dutch patients suffering from chronic diseases. The association between HRQol and severity of disease (IGA-P) was assessed. RESULTS: A total of 212 completed questionnaires were received. A total of 169 patients met the ROME-II-criteria for diagnosis of IBS. Of those, 18% suffered from IBS with diarrhea predominance, 19% from IBS with constipation predominance and 51% reported an alternating stool pattern. Severe abdominal pain (IGA-P >60mm on a 100mm VAS) was reported by 65%. Sufficient differences between the IBS-population and the Dutch population were measured for all dimensions of the SF36. SF-36 and IBSQoL outcomes were associated with disease severity. Patients regarded their health state as low: 0.62 (0.2) on a VAS and 0.66 (0.1) using the SF-6D algorithm. CONCLUSIONS: IBS has a significant impact on all dimensions of HRQol. Our findings are consistent with other studies. There is an unmet medical need in patients suffering from IBS in The Netherlands.

PCV67 USE OF CLOPIDOGREL AFTER ISCHEMIC VASCULAR EVENTS IN THE THE NETHERLANDS

PCV65 PERSISTENCE WITH DIFFERENT FORMULATIONS OF THE ANTIHYPERTENSIVE DRUG NIFEDIPINE Breekveldt-Postma NS, Herings RMC PHARMO Institute, Utrecht,The Netherlands OBJECTIVES: To assess differences in persistent use of nifedipine between the different formulations of nifedipine. METHODS: Incident nifedipine users were selected in the period of January, 1992 to December, 2001 from the PHARMO database which includes linked drug-dispensing records and hospital records of more than 1 million subjects in defined areas in The Netherlands. Patients with unaltered formulation and dosing frequency of nifedipine in the first year of follow-up with at least two dispensings were included in the study. Episodes of nifedipine use were constructed for each patient. The effect of formulation on persistence of use in the first episode with a maximum of one year was assessed using Cox’s proportional hazard analyses. Other determinants of persistent use that were taken into account were hospitalization and co-medication before and during nifedipine use. RESULTS: A total of 7902 incident users of nifedipine were included. One year persistence for nifedipine varied between different formulations and increased from 18% in patients using a non-retard formulation to 33% in patients using retard formulations up to 45% in patients using Adalat® OROS. The median length of the first episode was 82 days for non-retard formulations, 148 days for retard formulations and 285 days for Adalat® OROS. Multivariate analyses including gender, age, co-medication and hospitalization showed that patients using retard formulations were 1.4 times (RR: 1.42; 95%CI: 1.20–1.67) more persistent than patients using nonretard nifedipine. Patients using Adalat® OROS were 1.8 times (RR: 1.84; 95%CI: 1.54–2.20) more persistent than patients using non-retard nifedipine. A separate analysis without nonretard formulations showed that patients using Adalat® OROS were 1.3 times (RR: 1.34; 95%CI: 1.23–1.46) more persistent than patients using retard formulations. CONCLUSIONS: Patients using once daily Adalat® OROS are more persistent with nifedipine therapy than patients using twice daily retard formulations of nifedipine or trice daily nifedipine.

PGS10: TREATMENT PATTERNS AND HEALTH CARE COSTS OF MEBEVERINE-TREATED IBS PATIENTS:A CASE-CONTROL STUDY

SUMMARY Background Irritable bowel syndrome (IBS) is a functional disorder affecting the quality of life of patients. In the Nether-lands, mebeverine is currently the only medical treatment registered for IBS, although its efficacy is considered disputable.Objective To assess treatment patterns and associated health care cost in mebeverine users relative to matched controls.Methods A matched case-control study was performed using pharmacy data. Cases were mebeverine users as proxy forIBS patients. Controls were non-mebeverine users and matched to cases by age, gender and pharmacy. Prevalence and inci-dence of mebeverine use, concomitant drug use and hospitalizations were assessed in 3431 cases and 3431 controls. Con-comitant drug use and hospitalizations was also assessed in a subgroup of 1222 users of mebeverine and laxatives (proxy forconstipation-IBS) and their controls.Results Twelve per 1000 residents were ever-dispensed mebeverine in 1998. One-third of these mebeverine users usedlaxatives concomitantly. Concomitant drug use and hospitalizations were increased in mebeverine users. The odds ratiofor hospitalizations for gastrointestinal reasons was increased predominantly in mebeverine users with concomitant laxativeuse (OR:8.7; 95%CI [4.3–17.3]). Excess yearly costs for all concomitant medications were s94 [95%CI s79–s109] andfor hospital admissions s120 [s74–s166] per mebeverine user. In mebeverine users with concomitant laxative use thesecosts were s136 and s251 respectively.Conclusions In treated IBS patients, concomitant drug use and hospitalizations are increased relative to matched controls.Medical resource use and associated health care costs are particularly increased in mebeverine users using laxatives. Thetotal mean excess cost per patient per year is s482. Copyright # 2004 John Wiley & Sons, Ltd.key words—mebeverine; irritable bowel syndrome; matched case control study; incidence; laxatives; hospital morbidity;co-medication; health care costs