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 This study examines differences in four measures of oral BP exposure: treatment discontinuation, adherence, persistence, and non-persistence. Methods Among women aged ≥50 years who initiated oral BP therapy during 2002–2007 with at least three 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 two filled BP prescriptions during the study period, adherence was calculated for each year of follow-up using the proportion of days covered, modified to allow for stockpiling of prescription/refills overlap ≤30 days supply (mPDC). Persistence was quantified by treatment duration, allowing a gap of up to 60 days between prescription/refill days covered. Non-persistence was quantified by the periods without drug 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 three 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 age ≥75 years and somewhat lower (21.1%, p<0.001) for Asian women. During the first year, 60.4% achieved a mPDC of ≥75%, with demographic differences in adherence similar to that seen for treatment discontinuation. Over the three 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 one period of non-persistence during three years follow-up in excess of the 60 day allowable gap between prescription/refills (median cumulative non-persistence 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 Bisphosphonate 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 bisphosphonate exposure. We also found evidence that optimal adherence in the first year was highly predictive of optimal adherence in the subsequent one to two years. Hence, subgroups of patients receiving oral bisphosphonate drugs may require different levels of support and monitoring to maximize treatment benefit, especially based on early patterns of use.

Secular Trends in Long-Term Oral Bisphosphonate Use

“…Using the days' supply of dispensed drug (excluding prescription overlap > 30 days), with adherence calculated using the proportion of days covered, 6 we identified those continuing adherent BP treatment for at least 3 and 5 years, defined by adherence ≥ 60% each year as well as BP treatment within the 60 days prior to the end of the treatment period. Continuation rates were examined by year of BP initiation.…”

Risk of complete atypical femur fracture with Oral bisphosphonate exposure beyond three years

“…Bisphosphonate exposure was determined based on dispensing dates and days’ supply of each prescription. Stockpiling was allowed for prescriptions that overlapped 30 days or less; the second prescription took precedence when prescriptions overlapped for more than 30 days [ 13 ]. Each patient’s BP use was updated at each successive quarter (90-day interval) of follow-up after the index date.…”

Determinants of Oral Bisphosphonate Use Beyond 5 Years

“…Ongoing BP exposure (including all second-generation oral bisphosphonate drugs) was determined using the days supply of dispensed drugs, where prescription/refill gaps of 1 or 2 days were bridged, and stockpiling for prescriptions that overlapped for less than 30 days was allowed. 5 We considered each quarter of follow-up as being on (adherent) treatment if a woman had evidence of a PDC that was 0.6 or greater. 6…”

“…In previous studies, we examined treatment adherence for the first 3 years following BP initiation and have also shown that an adherence criteria of 0.6 (based on the proportion of days covered [PDC] by the dispensed days supply of BP) provides a practical approach for characterizing continued adherence in real-world clinical settings. 5,6 In the current study, we examined the association of demographic and clinical factors with BP continuation after the first 5 years of treatment. We also examined whether treatment continuation was determined by the era in which BP treatment was prescribed.…”