Summary. Original Investigation / Orijinal Araştırma 1 - PDF

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Original Investigation / Orijinal Araştırma 1 DO I: /tod Open, Prospective, Multi-Center, Two-Part Study of Patient Preference with Monthly Ibandronate Therapy in Women with Postmenopausal

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Original Investigation / Orijinal Araştırma 1 DO I: /tod Open, Prospective, Multi-Center, Two-Part Study of Patient Preference with Monthly Ibandronate Therapy in Women with Postmenopausal Osteoporosis Switched From Daily or Weekly Alendronate or Risendronate-BONCURE: Results of Turkish Sub-Study Günlük veya Haftalık Alendronat veya Risendronat Alan Postmenopozal Osteoporozlu Kadınlarda Aylık İbandronat İçin Hasta Tercihinin Değerlendirildiği Açık- Etiketli, Prospektif, Çok-Merkezi, İki-Aşamalı Çalışma-BONCURE: Türkiye Alt-Çalışması Nurten Eskiyurt, Jale İrdesel*, Vesile Sepici**, Hatice Uğurlu***, Yeşim Kirazlı****, Füsun Ardıç*****, Bülent Bütün******, Gülseren Akyüz*******, Lale Cerrahoğlu********, Ömer Faruk Şendur*********, Peyman Yalçın**********, Sema Öncel***********, Merih Sarıdoğan************, Tunay Sarpel*************, Mehmet Tosun**************, Yeşim Gökçe Kutsal***************, Kazım Şenel****************, Savaş Gürsoy*****************, Ferhan Cantürk******************, Hüseyin Demir*******************, Fatih Özdener********************, Hakan Öncel********************; BONCURE Study Group Istanbul University Istanbul School of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey *Uludag University School of Medicine, Department of Physical Medicine and Rehabilitation, Bursa, Turkey **Gazi University School of Medicine, Department of Physical Medicine and Rehabilitation, Ankara, Turkey ***Selcuk University School of Medicine, Department of Physical Medicine and Rehabilitation, Konya, Turkey ****Ege University School of Medicine, Department of Physical Medicine and Rehabilitation, Izmir, Turkey *****Pamukkale University School of Medicine, Department of Physical Medicine and Rehabilitation, Denizli, Turkey ******Akdeniz University School of Medicine, Department of Physical Medicine and Rehabilitation, Antalya, Turkey *******Marmara University School of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey ********Celal Bayar University School of Medicine, Department of Physical Medicine and Rehabilitation, Manisa, Turkey *********Adnan Menderes University School of Medicine, Department of Physical Medicine and Rehabilitation, Aydin, Turkey **********Ankara University School of Medicine, Department of Physical Medicine and Rehabilitation, Ankara, Turkey ***********Dokuz Eylul University School of Medicine, Department of Physical Medicine and Rehabilitation, Izmir, Turkey ************Istanbul University Cerrahpasa School of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey *************Cukurova University School of Medicine, Department of Physical Medicine and Rehabilitation, Adana, Turkey **************Karadeniz Technical University School of Medicine, Department of Physical Medicine and Rehabilitation, Trabzon, Turkey ***************Hacettepe University School of Medicine, Department of Physical Medicine and Rehabilitation, Ankara, Turkey ****************Ataturk University School of Medicine, Department of Physical Medicine and Rehabilitation, Erzurum, Turkey *****************Gaziantep University School of Medicine, Department of Physical Medicine and Rehabilitation, Gaziantep, Turkey ******************Ondokuz Mayis University School of Medicine, Department of Physical Medicine and Rehabilitation, Samsun, Turkey *******************Erciyes University School of Medicine, Department of Physical Medicine and Rehabilitation, Kayseri, Turkey ********************Roche Pharmaceuticals, Istanbul, Turkey Summary Aim: BONCURE (Bonviva for Current Bisphosphonate Users Regional European Trial), aimed to evaluate patient preference with monthly ibandronate in women with postmenopausal osteoporosis who previously received daily or weekly alendronate or risendronate. Materials and Methods: This prospective, open-label study consisted of two sequential stages, Part A (screening) and Part B (treatment). Patients enrolled into Part A completed the Candidate Identification Questionnaire (CIQ). In Part B, after completing the Osteoporosis Patient Satisfaction Questionnaire (OPSAT- Q), patients received monthly oral ibandronate 150 mg for 6 months. Following treatment, patients completed the OPSAT-Q and Preference Questionnaire. Results: A total of 223 patients (mean age, 63.7±9.51 years) were enrolled in Part A from Turkey. Among them, 103 (46.2%) answered YES to at least one CIQ question. The mean composite OPSAT-Q domain scores increased for convenience (mean change, 15.3±17.7 points), quality of life (10.4±20.4 points), overall satisfaction (11.9±22.7 points), and side effects (3.3±18.8 points). At month 6, 177 subjects (92.7%) preferred once-monthly dosing schedule and 99.0% were compliant ( 80%) with study treatment. Thirty (15.6%) subjects experienced mild to moderate adverse events, mostly gastrointestinal. Conclusion: Postmenopausal women with osteoporosis prefer and are more satisfied and compliant with monthly dosing of ibandronate than daily or weekly bisphosphonate treatment. (Turkish Journal of Osteoporosis 2012;18:1-7) Key words: Bisphosphonate, ibandronate, postmenopausal osteoporosis, patient preference Address for Correspondence/Yaz flma Adresi: Nurten Eskiyurt MD, İstanbul University İstanbul School of Medicine, Department of Physical Medicine and Rehabilitation, İstanbul, Turkey Phone: GSM: Received/Geliş Tarihi: Accepted/Kabul Tarihi: Turkish Journal of Osteoporosis, published by Galenos Publishing./Türk Osteoporoz Dergisi, Galenos Yayınevi taraf ndan bas lm flt r. 2 Patient Preference with Monthly Ibandronate Therapy in Postmenopausal Osteoporosis-BONCURE Turkey Turkish Journal of Osteoporosis 2012;18:1-7 Özet Amaç: BONCURE (Mevcut Bisfosfonat Kullanıcıları İçin Bonviva Bölgesel Avrupa Çalışması) ile daha önce günlük veya haftalık alendronat veya risendronat alan postmenopozal osteoporozu olan kadınlarda aylık ibandronat için hasta tercihinin değerlendirilmesi amaçlandı. Gereç ve Yöntemler: Bu prospektif, açık-etiketli çalışma, iki ardışık aşamadan oluşmuştur: A (tarama) ve B (tedavi) aşaması. A aşamasına kaydolan hastalar Aday Kimlik Anketi (CIQ) tamamladı. B aşamasında, Osteoporoz Hasta Memnuniyeti Anketi (OPSAT Q) tamamladıktan sonra, hastalar 6 ay boyunca aylık oral 150 mg ibandronat aldı. Tedaviden sonra, hastalar OPSAT-Q ve Tercihi Anketi tamamladı. Bulgular: Türkiye den 223 hasta (yaş ortalaması 63,7±9,51) A aşamasına dahil edildi. Bunların arasında, 103 ü (%46,2) en az bir CIQ sorusunu EVET yanıtladı. Ortalama bileşik OPSAT-Q alan puanları; kolaylık (ortalama değişiklik, 15,3±17,7 puan), yaşam kalitesi (10,4±20,4 puan), genel memnuniyet (11,9±22,7 puan) ve yan etkiler (3,3±18,8 puan) için arttı. Altıncı ayda 177 hasta (%92,7) bir kez aylık doz programını tercih etti ve %99,0 u çalışma tedavisi ile uyumlu ( %80) idi. Otuz hasta (%15,6) çoğunlukla gastrointestinal olan hafif ve orta şiddette advers olay yaşadı. Sonuç: Postmenopozal osteoporozu olan kadınlar, günlük veya haftalık bifosfonat tedavisine göre aylık ibandronatı daha çok tercih etmekte ve bu tedavi ile daha memnun ve uyumlu olmaktadır. (Türk Os te opo roz Dergisi 2012;18:1-7) Anah tar ke li me ler: Bifosfonat, ibandronat, postmenopozal osteoporoz, hasta tercihi Introduction Osteoporosis is a major public health issue affecting one in three postmenopausal women (1,2). Currently, bisphosphonates are considered to be the gold standard for the treatment of postmenopausal osteoporosis. Bisphosphonates decrease the incidence of vertebral and nonvertebral fractures, increase bone mass, and normalize bone turnover to premenopausal levels (3,4). However, bisphosphonates have complex dosing instructions and side effects, which limit their clinical utility (5,6). Therefore, patient compliance and persistence with long-term therapy are main obstacles of bisphosphonate treatment. It has been shown that 47% of postmenopausal women on oral bisphosphonate had suboptimal adherence at 6 months (7). Dose frequency of bisphosphonates is traditionally decreased for patients to comply with long-term therapy (8,9). Reducing the frequency of the intake of oral bisphosphonates may beneficially impact the attitude of patients towards compliance and further persistence (10). It is known that the reduction of daily dose frequency is associated with better adherence, patient compliance, greater efficacy, higher quality of life, and patient satisfaction in chronic diseases (8,11). Less frequent dosing with weekly and monthly oral regimens of bisphosphonates are generally preferred by patients over daily dosing (12,13). Currently, monthly bisphosphonate dosing regimens that increased patients preference and adherence over weekly regimens are treatment of choice for bisphosponates (14,15). Ibandronate is the first nitrogen-containing oral bisphosphonate for osteoporosis that can be administered in a monthly regimen. In a Phase III study, oral ibandronate both as daily and intermittent dosing regimens showed significant bone mineral density increases and reduction in the risk of vertebral fractures, compared to placebo (16). The MOBILE study showed that monthly oral administration of 100 mg and 150 mg ibandronate regimens were as effective as 2.5 mg daily oral ibandronate and well tolerated (17,18). In the recent studies, patients previously using weekly bisphosphonates (alendronate) reported improved satisfaction and preference with monthly ibandronate dosing (19-21). To collect further regional data on preference of patients for different dosing regimens of bisphosphonates, BONCURE (Bonviva for Current Bisphosphonate Users Regional European Trial) study evaluated the patients satisfaction, preference and compliance, and tolerability of monthly ibandronate 150 mg in women with postmenopausal osteoporosis who had previously received weekly or daily alendronate or risedronate by using a validated satisfaction instrument relevant to treatment for osteoporosis (Osteoporosis Patient Satisfaction Questionnaire, OPSAT-Q). This report represents the results of the BONCURE study for the Turkish sub-population. Materials and Methods Overall study design and study population This was a prospective, open-label, multicenter, international study consisting of two sequential stages, Part A (screening) and Part B (treatment) on postmenopausal women. The study was conducted in 43 centers from Croatia, Bosnia&Herzegovina, Macedonia, Albania, Turkey, Serbia. This report represents the results of 223 patients whose data are submitted from 20 sites in Turkey. All postmenopausal women, who had applied to the outpatient clinics at the study sites receiving once-daily or once-weekly alendronate or risedronate for the treatment or prevention of osteoporosis for a minimum of 3 months, and were able to understand and willing to comply with the study treatment requirements were enrolled into Part A of the study. Patients enrolled into Part A completed the Candidate Identification Questionnaire (CIQ) and among them those willing to comply with the protocol requirements, not hypersensitive to bisphosphonates, be able to stand or sit upright for at least 60 min, and without any medical condition or concomitant medication that could influence the study results or represent a safety hazard for the patient were enrolled to Part B of the study. In Part B, patients completed the OPSAT-Q and received monthly oral biphosphonate therapy (ibandronate 150 mg once-monthly, Bonviva 150 mg, Roche, Istanbul, Turkey) for 6 months. The patients completed the OPSAT-Q and Preference Questionnaire (Pref-Q), and provided a blood sample for laboratory safety tests at baseline assessment. Monthly ibandronate dosing was started one week after the last weekly bisphosphonate dose (with a window of up to 7 days). All patients were instructed to take supplemental calcium and vitamin D for the full duration of the study. All participants provided written informed consent before participating in the Part A and Part B of the study. The study was approved by the institutional ethics committees of each study center and conducted in accordance with the latest version of Declaration of Helsinki. Turkish Journal of Osteoporosis ;18:1-7 Patient Preference with Monthly Ibandronate Therapy in Postmenopausal Osteoporosis-BONCURE Turkey Study Assessment Tools Candidate Identification Questionnaire (CIQ) CIQ was completed by all of the subjects enrolled to Part A to determine the tendency for general preference of dosing schedule, previous gastrointestinal side effects and compliance to previous osteoporosis medication. In the CIQ, patients were asked to answer either yes or no to the following 3 questions: (1) I would prefer a monthly oral dosing schedule to my current (daily or weekly) dosing schedule, (2) More than once per month, I have experienced stomach upset within 48 hours of taking my osteoporosis medication, (3) Over the past 3 months, I have missed taking 3 or more doses of my current (daily or weekly) osteoporosis medication. Osteoporosis Patients Satisfaction Questionnaire (OPSAT-Q) The OPSAT-Q is a validated questionnaire designed to capture satisfaction with bisphosphonate treatment (22). It comprises 16 questions and four domains: convenience (questions 1 6), quality of life (questions 7 and 8), overall satisfaction (questions 9 and 10), and side effects (questions 11 16). All items were scored such that higher scores represented greater satisfaction or less bother and frequency of side effects. Treatment satisfaction was measured with the OPSAT-Q composite satisfaction score (OPSAT- Q CSS), which was the average of the scores from the four domains of the OPSAT-Q converted to a point scale. Preference Questionnaire (Pref-Q) All patients were asked to answer the Pref-Q at the end of the study (month 6) to define their preference for either monthly ibandronate or daily or weekly alendronate or risedronate. Study end-points The primary end-point was the proportion of current daily or weekly bisphosphonate users who answer YES to any of the questions in the CIQ for Part A of the study and the proportion of patients who report preference for either monthly ibandronate or daily or weekly alendronate or risedronate for Part B of the study. For safety evaluation, physical examination and laboratory tests findings, adverse events and concomitant medications were recorded throughout the study. Statistical Analysis The primary endpoint of Part A study was analyzed on all of the patients enrolled into collected from Part A. The study endpoints collected from Part B were analyzed in three analysis population: intent-to-treat (ITT) population which included all patients who received at least one dose of study medication, per protocol (PP) population which excluded all patients in the ITT population who significantly violated the study protocol, and safety analysis population which included all patients who received a dose of study medication and had at least one post-baseline safety measurement. The subjects who answered YES to at least one of the three CIQ questions are in the group in the analysis of data in PART B, and subjects who answered NO to all of the CIQ questions are in the group. Descriptive statistics were provided for all of the study data (e.g. mean, standard deviation, frequency, percentage). The Cochran- Mantel-Haenszel test was used to test the primary hypothesis which was, proportion of patients satisfied with once-monthly daily dosing of ibandronate after 6 months of use between the and groups. The analysis was adjusted with the history of osteoporotic fracture. The Breslow-Day test was used to assess the homogeneity of the odds ratio among the categories of the history of osteoporotic fracture. The absolute change from baseline satisfaction score at month 6, in both composite score and individual domain scores, was calculated. The distribution of the primary end- Table 1. Demography and osteoporosis history of patients enrolled into Part A of the study Demography Patients enrolled into Part A (n=223) Age (years) 63.7±9.51 Weight (kg) 64.2±10.2 Height (cm) 154.9±6.8 Body mass index (kg/m 2 ) 26.8±4.3 Time since menopause (months) 210.5±115.1 Osteoporosis history Positive history of fractures as an adult 55 (25.5%) Positive history of osteoporosis-related fragility fracture in a first-degree relative 38 (17.6%) Current smoker 25 (11.6%) Time from osteoporosis diagnosis 78.3±50.9 months 6.5±4.2 years Data are given as n (%) or mean±standard deviation Table 2. Previous and current diseases, and previous treatments reported in patients enrolled into Part A of the study Previous or current diseases Patients enrolled into Part A (n=223) Any disease 149 (66.8%) Vascular disorders 93 (41.7%) Metabolic and nutritional disorders 50 (22.4%) Musculoskeletal and connective tissue disorders 25 (11.2%) Cardiac disorder 18 (8.1%) Endocrine disorders 16 (7.2%) Gastrointestinal disorders 16 (7.2%) Psychiatric disorders 15 (6.7%) Nervous system disorders 10 (4.5%) Others 40 (17.9%) Previous treatments Previous treatments not associated with osteoporosis 12 (5.4%) Previous treatments related to osteoporosis 215 (96.4%) Previous calcium/vitamin D dietary supplement 111 (49.8%) Data are given as n (%) 4 Patient Preference with Monthly Ibandronate Therapy in Postmenopausal Osteoporosis-BONCURE Turkey Turkish Journal of Osteoporosis 2012;18: % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Total 77.9 Fracture history (+) Fracture history (-) Total Figure 1. Percentage of subjects with positive, negative or no change in CSS by CIQ-group and history of fractures in ITT population. p= in Cochran-Mantel-Haenszel test Table 3. Laboratory data at baseline and month 6 Total Baseline Month 6 Patients enrolled to Safety Part A population (n=223) (n=192) White blood cell count (109/L) 6.7± ±1.7 Platelets (109/L) 264.7± ±59.6 Hemoglobin (g/dl) 13.1± ±1.1 Hematocrit (%) 38.9± ±3.1 ALT (U/L) 18.5± ±9.8 Creatinine (mg/dl) 0.77± ±0.17 BUN (mg/dl) 15.4± ±4.8 Albumin (g/dl) 4.4± ±0.4 Sodium (mmol/l) 140.7± ±2.6 Chloride (mmol/l) 104.5± ±3.1 Total calcium (mg/dl) 9.4± ±0.4 Phosphate (mg/dl) 3.6± ±0.5 Data are given as mean±standard deviation Total No change Negative change Positive change point variable (positive/no change/negative in CSS score) was compared between the CIQ-groups using Pearson chi-square test. The change from baseline satisfaction score and domain scores at month 6 was analyzed using a Wilcoxon test. Mann-Whitney U test was used to compare the domain score changes between the CIQ groups. Statistical significance level was defined as p 0.05. Results Study Population A total of 223 patients (mean age, 63.7±9.51 years) were enrolled in Part A of the study, of which 23 did not continue to Part B (6 patients did not comply selection criteria at entry, 1 patient did not cooperate, 15 patients withdrew consent, and 1 patient had administrative/other problem) enrolling 200 patients to Part B. Four patients enrolled to Part B did not start the study medication, 8 patients were excluded due to major deviation or non-compliance, and 4 patients did not have any safety data, revealing 196 patients for ITT population, 188 patients for per protocol population, and 192 patients for safety population. The demography and osteoporosis history of patients enrolled into Part A were summarized in Table 1. Among patients enrolled into Part A of the study, 149 (66.8%) had previous or current systemic diseases and 96.4% had previously received treatments related to osteoporosis (Table 2). The laboratory results at baseline were summarized in Table 3. Serum calcium and phosphate levels were abnormal in 9 (4.0%) and 5 (2.2%) patients, respectively. CIQ Results Of the 223 subjects enrolled in Part A
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