title: Predicting Adherence and Persistence with Oral Bisphosphonate Therapy in an Integrated Health Care Delivery System.
abstract: BACKGROUND
  Examining drug exposure is essential to pharmacovigilance, especially for bisphosphonate (BP) therapy.
  
  
  OBJECTIVE
  To examine differences in 4 measures of oral BP exposure: treatment discontinuation, adherence, persistence, and nonpersistence.
  
  
  METHODS
  Among women aged ≥ 50 years who initiated oral BP therapy during 2002-2007 with at least 3 years of health plan membership follow-up, discontinuation was defined by evidence of no further treatment during the study observation period. Among those with at least 2 filled BP prescriptions during the study period, adherence was calculated for each year of follow-up using the (modified) proportion of days covered (mPDC) metric that allows for stockpiling of prescription/refills overlap ≤ 30 days supply. Persistence was quantified by treatment duration, allowing a gap of up to 60 days between prescription/refill days covered. Nonpersistence was quantified by the periods without drugs outside this allowable gap. Multivariable logistic regression was used to compare age and race groups and the relationships of early adherence (adherence during the first year) with subsequent adherence.
  
  
  RESULTS
  Among 48,390 women initiating oral BP therapy and followed for 3 years, 26.7% discontinued in year 1, and 14.7% of the remaining 35,456 women discontinued in year 2. Discontinuation rates were slightly higher (29.4%, P < 0.001) for women aged ≥ 75 years and somewhat lower (21.1%, P < 0.001) for Asian women. During the first year, 60.4% of the women achieved an mPDC of ≥ 75%, with demographic differences in adherence similar to that seen for treatment discontinuation. Over the 3 years, the median mPDC levels for BP therapy were 86%, 84%, and 85% in years 1, 2, and 3, respectively, for those receiving treatment. Cumulative persistence was 2.3 years (median, IQR = 1.0-3.0) overall and slightly greater for Asian versus white women and lower for older women. There were 18,174 (42.9%) women with at least 1 period of nonpersistence during 3 years follow-up in excess of the 60-day allowable gap between prescription/refills (median cumulative nonpersistence = 0.65, IQR = 0.30-1.25 years). Women with mPDC ≥ 75% during the first year had a 12-fold and 6-fold increased odds of mPDC ≥ 75% during year 2 and year 3, respectively.
  
  
  CONCLUSIONS
  BP discontinuation rates are highest for women during the first year. Among those continuing treatment in subsequent years, adherence rates were relatively stable. Persistence and adherence varied slightly by age and was somewhat higher in Asians, contributing to differences in cumulative BP exposure. We also found evidence that optimal adherence in the first year was highly predictive of optimal adherence in the subsequent 1-2 years. Hence, subgroups of patients receiving oral BP drugs may require different levels of support and monitoring to maximize treatment benefit, especially based on early patterns of use.
  
  
  BACKGROUND
  This study was supported by grants from the Kaiser Permanente Northern California Community Benefit Program and the National Institutes of Health, 1R01AG047230-01A1. The opinions expressed in this publication are solely the responsibility of the authors and do not represent the official views of Kaiser Permanente or the National Institutes of Health. Hui, Yi, and Chandra have received past research funding from Amgen not related to the current study. Adams has received research funding from Amgen, Merck, and Otsuka not related to the current study. Niu has received research funding from Bristol-Myers Squibb not related to the current study. Ettinger has received past legal fees in litigation involving Fosamax. Lo has received past research funding from Amgen and current research funding from Sanofi not related to the current study. The data from this study were presented at the Academy of Managed Care Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, California. Study concept and design were contributed primarily by Hui and Lo, along with Adams, Niu, Yi, and Ettinger. Hui took the lead in data collection, along with Chandra, and data interpretation was performed by Niu, Yi, and Lo, along with the other authors. The manuscript was written by Hui, Adams, and Lo, along with Niu, Yi, and Ettinger, and revised by Ettinger, Hui, Lo, and Niu, along with the other authors.
authors.affiliation: 1 Pharmacy Outcomes Research Group, Kaiser Permanente California, Oakland.
authors.forename: Rita L
authors.initials: RL
authors.lastname: Hui
authors.affiliation: 3 Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena.
authors.forename: Annette L
authors.initials: AL
authors.lastname: Adams
authors.affiliation: 4 Pharmacy Outcomes Research Group, Kaiser Permanente California, Downey.
authors.forename: Fang
authors.initials: F
authors.lastname: Niu
authors.affiliation: 2 Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ettinger
authors.affiliation: 3 Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena.
authors.forename: David K
authors.initials: DK
authors.lastname: Yi
authors.affiliation: 2 Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Malini
authors.initials: M
authors.lastname: Chandra
authors.affiliation: 2 Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Joan C
authors.initials: JC
authors.lastname: Lo
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001213:Asian; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D003695:Delivery of Health Care / Q000706:statistics & numerical data*; D019033:Delivery of Health Care, Integrated; D004164:Diphosphonates / Q000627:therapeutic use*; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005006:Ethnicity; D005260:Female; D006801:Humans; D014481:United States; D044465:White People; D016903:Drug Monitoring
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates