Günlük esnek veya sabit doz risedronat rejimiuygulanan postmenopozal osteoporozlu kadınlardatedaviye uyum, devam etme ve tercih sonuçları:Çok merkezli, prospektif, paralel grup çalışma

Yıl 2015, , 67 - 74, 19.03.2015

Aydan Oral Roman Lorenc For The Flınt-act Study Investigators

https://doi.org/10.3944/AOTT.2015.14.0082

Öz

Amaç: Çalışmanın amacı günlük risedronat (5 mg) tedavisini üç farklı zaman rejiminde (A, ‘kahval¬tıdan önce’; B, ‘öğünler arası’; C, ‘yatmadan önce’) olmak üzere sabit doz şeklinde veya esnek doz bazlı alan hastalarda tedaviye uyum ve devam etme düzeylerini değerlendirmekti. Ayrıca hastaların doz re¬jimlerine yönelik tercihleri ve doz rejimlerinin idrar NTX-I düzeyi üzerine etkileri de değerlendirildi.

Çalışma planı: Çalışma 448 hastanın her birinin tedavi sekanslarının diziliminin değiştirilmesi (per¬mutasyon) (ABC, BCA, gibi) ile oluşan altı farklı tedavi grubundan birine rasgele atandığı bir çapraz tedavi fazı (3x1 hafta) ve her bir hastanın günlük esnek (rejim A,B veya C’den her hangi biri) ve sabit zamanlı (yalnızca rejim A, ya da B veya C) rejimlerden birine 23 hafta süreyle randomize edildiği has¬tanın tercihi fazını içeriyordu.

Bulgular: 433 hasta ikinci faza katıldı; %49.7’si esnek rejimi ve %50.3’ü sabit rejimi tercih etti. Esnek ve sabit tedavi rejimleri arasında bileşik olarak tedaviye hem uyum hem de devamlılık gösteren, olumlu hareket edenler olarak nitelenen hasta oranı açısından anlamlı bir fark saptanmazken (sırasıyla %54.4 ve %53.7, p=0.8803), iki tedavi rejimi arasında tedaviye devam etme açısından esnek rejim lehine anlamlı bir fark belirlendi (p=0.0306). Tedavi uyumu konusunda esnek ve sabit rejimler arasında anlamlı bir farklılık gözlenmedi (p=0.4611). İdrar NTX-I düzeylerindeki değişiklikler iki rejim arasında anlamlı bir farklılık göstermedi. Son vizitte esnek rejim grubundaki hastaların %51’i ve sabit rejimdeki hastala¬rın %55’i kullanılan risedronat rejimini mükemmel veya çok iyi olarak değerlendirdi (p=0.1440).

Çıkarımlar: Bu küçük ölçekli, seçilmiş hasta grubundan elde edilen verilere dayanılarak esnek doz günlük risedronat tedavisinin tedavi uyumu ve devamlılığı açısından kayda değer bir alternatif sundu¬ğu düşünülebilir.

Anahtar Kelimeler

Tedavi uyumu; günlük sabit doz; günlük esnek doz; osteoporoz; tedaviye devam etme; risedronat

Compliance, persistence, and preference outcomes of postmenopausal osteoporotic women receiving a flexible or fixed regimen of daily risedronate: A multicenter, prospective, parallel group study

Öz

Objective: The aim of this study was to examine the level of compliance and persistence in patients with postmenopausal osteoporosis (OP) receiving daily risedronate (5 mg) with either fixed dosing of three different timing regimens (A: before breakfast; B: in-between meals; C: before bedtime) or with flexible dosing and the effect on urinary N-terminal telopeptide of Type 1 collagen (NTX-1).

Methods: The study included 448 patients with postmenopausal OP. Patients were randomly assigned into six treatment groups each with a permutation of the treatment sequence (ABC, BCA, etc.) in the crossover phase (3x1 week) and randomized to 23 weeks of either the daily flexible (either regimen A, B or C) or fixed timing (only regimen A, B, or C) in the patient’s preference phase. Urinary NTX-1 was tested.

Results: A total of 433 patients participated in the patient’s preference phase (49.7% preferred flexible and 50.3% fixed timing). There was no significant difference between the proportion of responders who were both compliant and persistent in the flexible (54.4%) and fixed regimens (53.7%) (p=0.8803). A significant difference between the flexible and fixed regimens was seen in persistence in favor of the flexible regimen (p=0.0306). There was no significant difference between the flexible and fixed regimens in terms of compliance (p=0.4611). Change in urinary NTX-1 did not show any difference between the two regimens. At the final visit, 51% of patients in the flexible and 55% in the fixed regimen group considered the used risedronate regimen as excellent or very good (p=0.1440).

Conclusion: A flexible dosing with daily risedronate appears be a valuable option in terms of compliance and persistence for patients with postmenopausal OP.

Anahtar Kelimeler

Compliance, daily fixed dosing, daily flexible dosing, osteoporosis, persistence, risedronate

Kaynakça

• Ross S, Samuels E, Gairy K, Iqbal S, Badamgarav E, Siris E. A meta-analysis of osteoporotic fracture risk with medication non- adherence. Value Health 2011;14:571-81.
• Imaz I, Zegarra P, González-Enríquez J, Rubio B, Alcazar R, Amate JM. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta- analysis. Osteoporos Int 2010;21:1943-51.
• Silverman SL, Schousboe JT, Gold DT. Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos Int 2011;22:21-6.
• Cramer JA, Gold DT, Silverman SL, Lewiecki EM. A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 2007;18:1023-31.
• International Osteoporosis Foundation. The adherence gap: Why osteoporosis patients don’t continue with treatment; 2005 [cited 2011 October 17]. Available from: http://www.iofbone- health.org/publications/the-adherence-gap.html.
• Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008;1:CD004523.
• Jansen JP, Bergman GJ, Huels J, Olson M. The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonver- tebral-nonhip fractures in osteoporosis: a network meta-analysis. Semin Arthritis Rheum 2011;40:275-84.e1-2.
• Reginster JY. Antifracture efficacy of currently available thera- pies for postmenopausal osteoporosis. Drugs 2011;71:65-78.
• Gates BJ, Das S. Risedronate’s Role in Reducing Hip Fracture in Postmenopausal Women with Established Osteoporosis. Clin Med Insights Arthritis Musculoskelet Disord 2012;5:1-14.
• Zhong ZM, Chen JT. Anti-fracture efficacy of risedronic acid in men: A meta-analysis of randomized controlled trials. Clin Drug Investig 2009;29:349-57.
• Clemmesen B, Ravn P, Zegels B, Taquet AN, Christiansen C, Reginster JY. A 2-year phase II study with 1-year of follow-up of risedronate (NE-58095) in postmenopausal osteoporosis. Os- teoporos Int 1997;7:488-95.
• Mortensen L, Charles P, Bekker PJ, Digennaro J, Johnston CC Jr. Risedronate increases bone mass in an early postmenopausal popu- lation: two years of treatment plus one year of follow-up. J Clin En- docrinol Metab 1998;83:396-402.
• Hosking D, Adami S, Felsenberg D, Andia JC, Välimäki M, Benhamou L, et al. Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised, placebo-controlled study. Curr Med Res Opin 2003;19:383-94.
• Agrawal S, Krueger DC, Engelke JA, Nest LJ, Krause PF, Drinka PJ, et al. Between-meal risedronate does not alter bone turnover in nursing home residents. J Am Geriatr Soc 2006;54:790-5.
• Kendler DL, Ringe JD, Ste-Marie LG, Vrijens B, Taylor EB, Del- mas PD. Risedronate dosing before breakfast compared with dos- ing later in the day in women with postmenopausal osteoporosis. Osteoporos Int 2009;20:1895-902.
• Hanson DA, Weis MA, Bollen AM, Maslan SL, Singer FR, Eyre DR. A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telo- peptides in urine. J Bone Miner Res 1992;7:1251-8.
• Ste-Marie LG, Brown JP, Beary JF, Matzkin E, Darbie LM, Bur- gio DE, et al. Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-con- trolled, dose-ranging study. Clin Ther 2009;31:272-85.
• Huybrechts KF, Ishak KJ, Caro JJ. Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 2006;38:922-8.
• Weycker D, Macarios D, Edelsberg J, Oster G. Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int 2006;17:1645-52.
• Penning-van Beest FJ, Erkens JA, Olson M, Herings RM. Loss of treatment benefit due to low compliance with bisphosphonate therapy. Osteoporos Int 2008;19:511-7.
• Höer A, Seidlitz C, Gothe H, Schiffhorst G, Olson M, Hadji P, et al. Influence on persistence and adherence with oral bisphos- phonates on fracture rates in osteoporosis. Patient Prefer Adher- ence 2009;3:25-30.
• Halpern R, Becker L, Iqbal SU, Kazis LE, Macarios D, Badamg- arav E. The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitaliza- tions: a retrospective claims analysis of female health plan enroll- ees with osteoporosis. J Manag Care Pharm 2011;17:25-39.
• Cramer JA, Amonkar MM, Hebborn A, Altman R. Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 2005;21:1453-60.
• Penning-van Beest FJ, Goettsch WG, Erkens JA, Herings RM. Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis. Clin Ther 2006;28:236-42.
• Hadji P, Claus V, Ziller V, Intorcia M, Kostev K, Steinle T. GRAND: the German retrospective cohort analysis on compli- ance and persistence and the associated risk of fractures in osteo- porotic women treated with oral bisphosphonates. Osteoporos Int 2012;23:223-31.
• Landfeldt E, Ström O, Robbins S, Borgström F. Adherence to treatment of primary osteoporosis and its association to frac- tures-the Swedish Adherence Register Analysis (SARA). Os- teoporos Int 2012;23:433-43.
• Netelenbos JC, Geusens PP, Ypma G, Buijs SJ. Adherence and profile of non-persistence in patients treated for osteoporosis--a large-scale, long-term retrospective study in The Netherlands. Osteoporos Int 2011;22:1537-46.
• Li L, Roddam A, Gitlin M, Taylor A, Shepherd S, Shearer A, et al. Persistence with osteoporosis medications among postmeno- pausal women in the UK General Practice Research Database. Menopause 2012;19:33-40.
• Siris ES, Pasquale MK, Wang Y, Watts NB. Estimating bisphos- phonate use and fracture reduction among US women aged 45 years and older, 2001-2008. J Bone Miner Res 2011;26:3-11.
• Wilkes MM, Navickis RJ, Chan WW, Lewiecki EM. Bisphos- phonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials. Osteoporos Int 2010;21:679-88.
• Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, et al. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2007;92:1296-304.
• Eastell R, Vrijens B, Cahall DL, Ringe JD, Garnero P, Watts NB. Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J Bone Miner Res 2011;26:1662-9.
• Silverman SL, Nasser K, Nattrass S, Drinkwater B. Impact of bone turnover markers and/or educational information on per- sistence to oral bisphosphonate therapy: a community setting- based trial. Osteoporos Int 2012;23:1069-74.
• Mitchell DY, Heise MA, Pallone KA, Clay ME, Nesbitt JD, Russell DA, et al. The effect of dosing regimen on the pharmaco- kinetics of risedronate. Br J Clin Pharmacol 1999;48:536-42.
• Barrett-Connor E, Wade SW, Do TP, Satram-Hoang S, Stewart R, Gao G, et al. Treatment satisfaction and persistence among postmenopausal women on osteoporosis medications: 12-month results from POSSIBLE US™. Osteoporos Int 2012;23:733-41.
• Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollen- dorf DA, et al. Medication compliance and persistence: terminol- ogy and definitions. Value Health 2008;11:44-7.
• Solomon DH, Brookhart MA, Tsao P, Sundaresan D, Andrade SE, Mazor K, et al. Predictors of very low adherence with medi- cations for osteoporosis: towards development of a clinical pre- diction rule. Osteoporos Int 2011;22:1737-43.
• Lee S, Glendenning P, Inderjeeth CA. Efficacy, side effects and route of administration are more important than frequency of dosing of anti-osteoporosis treatments in determining patient adherence: a critical review of published articles from 1970 to 2009. Osteoporos Int 2011;22:741-53.