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Published in: Osteoporosis International 5/2011

Open Access 01-05-2011 | Original Article

Adherence and profile of non-persistence in patients treated for osteoporosis—a large-scale, long-term retrospective study in The Netherlands

Authors: J. C. Netelenbos, P. P. Geusens, G. Ypma, S. J. E. Buijs

Published in: Osteoporosis International | Issue 5/2011

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Abstract

Summary

We analyzed 12-month compliance for all ten oral osteoporosis drugs in the Netherlands by medication possession ratio (MPR ≥ 80%) in 105,506 patients, and persistence in 8,626 starters indicated high MPR (91%), low persistence (43%), and no restart in 78% of the stoppers after 18 months.

Introduction

We studied compliance and persistence for all available oral osteoporosis medications on a national scale in the Netherlands.

Methods

We analyzed the IMS Health’s longitudinal prescription database, which represents 73% of all pharmacies in the Netherlands. Twelve-month compliance was measured by medication possession ratio (MPR) in a cross-sectional cohort of 105,506 patients who received at least three prescriptions. Twelve-month persistence (no gap in refills for >6 months) was measured in all 8,626 consecutive patients starting therapy, with a further follow-up in non-persistent patients during an additional 18 months for evaluation of switching, restart, or definitive stopping oral medication. Multivariate logistic regression analysis was used to analyze the odds ratios (ORs) with 95% confidence intervals (CI) of characteristics of non-persistence.

Results

MPR of ≥80% was found in 91% of patients. Persistence was 43% (range, 29–52%). Persistence was related to age >60 years (ORs, 1.41 to 1.64), pharmacy outside very dense urban area (ORs, 1.39 to 1.44), additional use of calcium and/or vitamin D supplementation (OR, 1.26 and CI, 1.13, 1.39) and use of glucocorticoids (OR, 0.65 and CI, 0.59, 0.72) or cardiovascular medication (OR, 0.88 and CI, 0.79, 0.97). Of non-persistent patients, 22% restarted within 18 months with oral osteoporosis drugs.

Conclusions

One-year compliance for all available oral osteoporosis medications was high, but 1-year persistence was low. Most stoppers did not restart or switch during an additional 18-month follow-up. These data indicate a major failure to adequately treat patients at high risk for fractures in daily practice.
Literature
2.
go back to reference Van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England. Bone 29:517–522PubMedCrossRef Van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England. Bone 29:517–522PubMedCrossRef
3.
go back to reference Tosteson AN, Burge RT, Marshall DA, Lindsay R (2008) Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations. Am J Manag Care 14:605–615PubMed Tosteson AN, Burge RT, Marshall DA, Lindsay R (2008) Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations. Am J Manag Care 14:605–615PubMed
4.
go back to reference Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301:513–521PubMedCrossRef Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301:513–521PubMedCrossRef
5.
go back to reference Ryg J, Rejnmark L, Overgaard S, Brixen K, Vestergaard P (2009) Hip fracture patients at risk of second hip fracture: a nationwide population-based cohort study of 169,145 cases during 1977–2001. J Bone Miner Res 24:1299–1307PubMedCrossRef Ryg J, Rejnmark L, Overgaard S, Brixen K, Vestergaard P (2009) Hip fracture patients at risk of second hip fracture: a nationwide population-based cohort study of 169,145 cases during 1977–2001. J Bone Miner Res 24:1299–1307PubMedCrossRef
6.
go back to reference Van Geel TA, van Helden S, Geusens PP et al (2009) Clinical subsequent fractures cluster in time after first fractures. Ann Rheum Dis 68:99–102PubMedCrossRef Van Geel TA, van Helden S, Geusens PP et al (2009) Clinical subsequent fractures cluster in time after first fractures. Ann Rheum Dis 68:99–102PubMedCrossRef
7.
go back to reference Huntjens KM, Kosar S, van Geel TA, Geusens PP, Willems P, Kessels A, Winkens B, Brink P, van Helden S (2010) Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture. Osteoporos Int (in press) Huntjens KM, Kosar S, van Geel TA, Geusens PP, Willems P, Kessels A, Winkens B, Brink P, van Helden S (2010) Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture. Osteoporos Int (in press)
8.
go back to reference Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082PubMedCrossRef Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082PubMedCrossRef
9.
go back to reference Solomon DH, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Brookhart MA (2005) Compliance with osteoporosis medications. Arch Intern Med 165:2414–2419PubMedCrossRef Solomon DH, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Brookhart MA (2005) Compliance with osteoporosis medications. Arch Intern Med 165:2414–2419PubMedCrossRef
10.
go back to reference Feldstein AC, Weycker D, Nichols GA et al (2009) Effectiveness of bisphosphonate therapy in a community setting. Bone 44:153–159PubMedCrossRef Feldstein AC, Weycker D, Nichols GA et al (2009) Effectiveness of bisphosphonate therapy in a community setting. Bone 44:153–159PubMedCrossRef
11.
go back to reference Kothawala P, Badamgarav E, Ryu S et al (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501PubMedCrossRef Kothawala P, Badamgarav E, Ryu S et al (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501PubMedCrossRef
12.
go back to reference Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47PubMedCrossRef Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47PubMedCrossRef
13.
go back to reference Seeman E, Compston J, Adachi J et al (2007) Non-compliance: the Achilles’ heel of anti-fracture efficacy. Osteoporos Int 18:711–719PubMedCrossRef Seeman E, Compston J, Adachi J et al (2007) Non-compliance: the Achilles’ heel of anti-fracture efficacy. Osteoporos Int 18:711–719PubMedCrossRef
14.
go back to reference Siris ES, Selby PL, Saag KG et al (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122:S3–S13PubMedCrossRef Siris ES, Selby PL, Saag KG et al (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122:S3–S13PubMedCrossRef
17.
go back to reference Hiligsmann M, Rabema V, Gathon HJ, Ethgen O, Reginster JY (2010) Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif Tissue Int 86:202–210PubMedCrossRef Hiligsmann M, Rabema V, Gathon HJ, Ethgen O, Reginster JY (2010) Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif Tissue Int 86:202–210PubMedCrossRef
18.
go back to reference Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928PubMedCrossRef Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928PubMedCrossRef
19.
go back to reference Siris ES, Harris ST, Rosen CJ et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022PubMedCrossRef Siris ES, Harris ST, Rosen CJ et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022PubMedCrossRef
20.
go back to reference Lekkerkerker F, Kanis JA, Alasyed N et al (2007) Adherence to treatment of osteoporosis: a need for study. Osteoporos Int 18:1311–1317PubMedCrossRef Lekkerkerker F, Kanis JA, Alasyed N et al (2007) Adherence to treatment of osteoporosis: a need for study. Osteoporos Int 18:1311–1317PubMedCrossRef
21.
go back to reference Briesacher BA, Andrade SE, Yood RA, Kahler KH (2007) Consequences of poor compliance with bisphosphonates. Bone 41:882–887PubMedCrossRef Briesacher BA, Andrade SE, Yood RA, Kahler KH (2007) Consequences of poor compliance with bisphosphonates. Bone 41:882–887PubMedCrossRef
22.
go back to reference Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG (2008) Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int 19:1613–1620PubMedCrossRef Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG (2008) Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int 19:1613–1620PubMedCrossRef
23.
go back to reference Penning-van Beest FJ, Erkens JA, Olson M (2008) Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis. Curr Med Res Opin 24:1337–1344PubMedCrossRef Penning-van Beest FJ, Erkens JA, Olson M (2008) Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis. Curr Med Res Opin 24:1337–1344PubMedCrossRef
24.
go back to reference Imaz I, Zegarra P, Gonzalez-Enriquez J et al (2009) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int (in press) Imaz I, Zegarra P, Gonzalez-Enriquez J et al (2009) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int (in press)
25.
go back to reference Brookhart MA, Avorn J, Katz JN et al (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256PubMedCrossRef Brookhart MA, Avorn J, Katz JN et al (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256PubMedCrossRef
26.
go back to reference Gold DT, Alexander IM, Ettinger MP (2006) How can osteoporosis patients benefit more from their therapy? Adherence issues with bisphosphonate therapy. Ann Pharmacother 40:1143–1150PubMedCrossRef Gold DT, Alexander IM, Ettinger MP (2006) How can osteoporosis patients benefit more from their therapy? Adherence issues with bisphosphonate therapy. Ann Pharmacother 40:1143–1150PubMedCrossRef
27.
go back to reference Briesacher BA, Andrade SE, Fouayzi H, Chan KA (2008) Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy 28:437–443PubMedCrossRef Briesacher BA, Andrade SE, Fouayzi H, Chan KA (2008) Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy 28:437–443PubMedCrossRef
28.
go back to reference Buurma H, Bouvy ML, De Smet PAGM et al (2008) Prevalence and determinants of pharmacy shopping behaviour. J Clin Pharm Ther 33:17–23PubMedCrossRef Buurma H, Bouvy ML, De Smet PAGM et al (2008) Prevalence and determinants of pharmacy shopping behaviour. J Clin Pharm Ther 33:17–23PubMedCrossRef
29.
go back to reference Sikka R, Xia F, Aubert RE (2005) Estimating medication persistency using administrative claims data. Am J Manag Care 11:449–457PubMed Sikka R, Xia F, Aubert RE (2005) Estimating medication persistency using administrative claims data. Am J Manag Care 11:449–457PubMed
30.
go back to reference Recker RR, Gallagher R, MacCosbe PE (2005) Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 80:856–861PubMedCrossRef Recker RR, Gallagher R, MacCosbe PE (2005) Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 80:856–861PubMedCrossRef
31.
go back to reference Cramer JA, Silverman S (2006) Persistence with bisphosphonate treatment for osteoporosis: finding the root of the problem. Am J Med 119:S12–S17PubMedCrossRef Cramer JA, Silverman S (2006) Persistence with bisphosphonate treatment for osteoporosis: finding the root of the problem. Am J Med 119:S12–S17PubMedCrossRef
32.
go back to reference Hosmer DW, Lemesbow S (1980) Goodness of fit tests for the multiple logistic regression model. Commun Stat A10:1043–1069CrossRef Hosmer DW, Lemesbow S (1980) Goodness of fit tests for the multiple logistic regression model. Commun Stat A10:1043–1069CrossRef
33.
go back to reference Penning-van Beest FJ, Goettsch WG, Erkens JA, Herings RM (2006) Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis. Clin Ther 28:236–242PubMedCrossRef Penning-van Beest FJ, Goettsch WG, Erkens JA, Herings RM (2006) Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis. Clin Ther 28:236–242PubMedCrossRef
34.
go back to reference Penning-van Beest FJ, Erkens JA, Olson M (2008) Loss of treatment benefit due to low compliance with bisphosphonate therapy. Osteoporos Int 19:511–517PubMedCrossRef Penning-van Beest FJ, Erkens JA, Olson M (2008) Loss of treatment benefit due to low compliance with bisphosphonate therapy. Osteoporos Int 19:511–517PubMedCrossRef
35.
go back to reference Rabenda V, Mertens R, Fabri V et al (2008) Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int 19:811–818PubMedCrossRef Rabenda V, Mertens R, Fabri V et al (2008) Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int 19:811–818PubMedCrossRef
36.
go back to reference Landfeldt E, Borgstrom F, Robbins S et al (2010) Adherence to treatment of osteoporosis in Sweden: the Swedish Adherence Register Analysis (SARA). Osteoporos Int 21(Suppl1):S252 Landfeldt E, Borgstrom F, Robbins S et al (2010) Adherence to treatment of osteoporosis in Sweden: the Swedish Adherence Register Analysis (SARA). Osteoporos Int 21(Suppl1):S252
37.
go back to reference Van den Boogaard CHA, Breekveldt-Postma NS, Borggreve SE et al (2006) Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study. Curr Med Res Opin 22:1757–1764PubMedCrossRef Van den Boogaard CHA, Breekveldt-Postma NS, Borggreve SE et al (2006) Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study. Curr Med Res Opin 22:1757–1764PubMedCrossRef
38.
go back to reference McCoombs JS, Thiebaud P, McLaughlin-Miley C, Shi J (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287CrossRef McCoombs JS, Thiebaud P, McLaughlin-Miley C, Shi J (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287CrossRef
40.
go back to reference Cooper A, Drake J, Brankin E et al (2006) Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 60:896–905PubMedCrossRef Cooper A, Drake J, Brankin E et al (2006) Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 60:896–905PubMedCrossRef
41.
go back to reference Weiss TW, Henderson SC, McHorney CA, Cramer JA (2007) Persistence across weekly and monthly bisphosphonates: analysis of US retail pharmacy prescription refills. Curr Med Res Opin 23:2193–2203PubMedCrossRef Weiss TW, Henderson SC, McHorney CA, Cramer JA (2007) Persistence across weekly and monthly bisphosphonates: analysis of US retail pharmacy prescription refills. Curr Med Res Opin 23:2193–2203PubMedCrossRef
42.
go back to reference Geusens PP, Lems WF, Verhaar HJ, Leusink G, Goemaere S, Zmierczack H, Compston J (2006) Review and evaluation of the Dutch guidelines for osteoporosis. J Eval Clin Pract 12:539–548PubMedCrossRef Geusens PP, Lems WF, Verhaar HJ, Leusink G, Goemaere S, Zmierczack H, Compston J (2006) Review and evaluation of the Dutch guidelines for osteoporosis. J Eval Clin Pract 12:539–548PubMedCrossRef
43.
go back to reference McDonald HP, Garg AX, Haynes RB (2002) Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA 288:2868–2879PubMedCrossRef McDonald HP, Garg AX, Haynes RB (2002) Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA 288:2868–2879PubMedCrossRef
44.
go back to reference Gleeson T, Iversen MD, Avorn J et al (2009) Interventions to improve adherence and persistence with osteoporosis medications: a systematic literature review. Osteoporos Int 20:2127–2134PubMedCrossRef Gleeson T, Iversen MD, Avorn J et al (2009) Interventions to improve adherence and persistence with osteoporosis medications: a systematic literature review. Osteoporos Int 20:2127–2134PubMedCrossRef
45.
go back to reference Clowes JA, Peel NF, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123PubMedCrossRef Clowes JA, Peel NF, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123PubMedCrossRef
46.
go back to reference Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD et al (2007) Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:1296–1304PubMedCrossRef Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD et al (2007) Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:1296–1304PubMedCrossRef
47.
go back to reference Solomon DH, Gleeson T, Iversen M et al (2010) A blinded randomized controlled trial of motivational interviewing to improve adherence with osteoporosis medications: design of the OPTIMA trial. Osteoporos Int 21:137–144PubMedCrossRef Solomon DH, Gleeson T, Iversen M et al (2010) A blinded randomized controlled trial of motivational interviewing to improve adherence with osteoporosis medications: design of the OPTIMA trial. Osteoporos Int 21:137–144PubMedCrossRef
48.
go back to reference Rossini M, Bianchi G, Di Munno O et al (2006) Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 16:914–921CrossRef Rossini M, Bianchi G, Di Munno O et al (2006) Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 16:914–921CrossRef
49.
go back to reference Ringe JD, Moller G (2009) Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis. Rheumatol Int 30:213–221CrossRef Ringe JD, Moller G (2009) Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis. Rheumatol Int 30:213–221CrossRef
50.
go back to reference Sheehy O, Kindundu CM, Barbeau M et al (2009) Differences in persistence among weekly different oral bisphosphonate medications. Osteoporos Int 20:1369–1376PubMedCrossRef Sheehy O, Kindundu CM, Barbeau M et al (2009) Differences in persistence among weekly different oral bisphosphonate medications. Osteoporos Int 20:1369–1376PubMedCrossRef
Metadata
Title
Adherence and profile of non-persistence in patients treated for osteoporosis—a large-scale, long-term retrospective study in The Netherlands
Authors
J. C. Netelenbos
P. P. Geusens
G. Ypma
S. J. E. Buijs
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 5/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-010-1372-5

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