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New bisphosphonate users who adhere to dosing recommendations at lower risk for fracture
Adherence to bisphosphonates among new users is associated with a significantly lower risk for osteoporotic fractures, according to data from a retrospective analysis of commercially insured Americans.
The caveat, however, is that a significant number of patients prescribed bisphosphonates do not reach a sufficient level of adherence to obtain clinical effectiveness from the medication, the researchers wrote. In their study of more than 30,000 patients, more than 40% took less than half the recommended doses.
Data on the relationship between osteoporosis medication adherence and fracture risk in commercially insured patients is dated and, for the most part, limited, Wade and colleagues wrote in their study.
They identified 33,558 new bisphosphonate users using medical and outpatient pharmacy claims acquired from Jan. 1, 2005, to April 30, 2008. All patients had their first osteoporosis medication filled during this time period and had continuous insurance coverage for 12 months or more before and after their first prescription was filled (defined as the index date).
The occurrence of any incident fracture 12 months or longer after the index date, but before the end of follow-up, was used to classify patients into a fracture or nonfracture cohort.
Wade and colleagues measured persistence — how long a patient remained on the drug before a significant gap or discontinuation — using a 90-day gap in therapy, and a sensitivity analysis was performed using a 60-day gap. Adherence was measured using the medication possession ratio (MPR), defined as the sum of day’s supply dispensed for the osteoporosis medication divided by the number of days in the observation period, according to the study.
More than half of patients included in the study (68.2%) had 24 months or more of follow-up and were included in a sub-analysis of MPR during 24 months. After 1 year of bisphosphonate treatment, 2.8% of patients had an osteoporosis-related fracture during the study period; most were nonvertebral, nonhip fractures (73.4%). Clinical vertebral fractures occurred among 17.1% and hip fractures among 9.5%.
Medication adherence, persistence
During the 12-month follow-up, 44.5% of patients had no refill gaps longer than 90 days. According to the 60-day sensitivity analysis, 39.9% of patients were persistent. Wade and colleagues observed a significant difference in persistence among patients taking fewer than five concomitant medications vs. those taking five or more concomitant medications (47.5% vs. 42.4%; P<.001).
At 12 months post-index, the median MPR was 0.61 for all bisphosphonates: 0.61 for alendronate; 0.61 for risedronate and 0.58 for ibandronate. Unadjusted MPR differed significantly by select patient characteristics. Less than half (39.2%) of bisphosphonate users were adherent during the first year. Compared with women, men were significantly more adherent (38.7% vs. 39.2%; P<.001); however, the mean MPR for 12 months was statistically higher among women than men (0.58 vs. 0.56).
Adherence varied by age group, geographic region and health plan type. Additionally, adherence was more common among those with a lower DCI score, a diagnosis code for osteopenia vs. osteoporosis, evidence of BMD testing in the pre-index period or no evidence of pre-index corticosteroid use.
Adherence linked to fracture
According to an unadjusted analysis, new bisphosphonate users who fractured after initiating therapy were more likely to have MPR of less than 0.5 compared with those who did not fracture during follow-up (50.4% vs. 44.2%; P<.001). MPR of more than 0.8 was less common among patients who fractured, however, compared with those who did not (34.9% vs. 39.3%; P<.001). Wade and colleagues reported that about one-third of patients in each fracture group — vertebral, hip, nonhip, nonvertebral — achieved an MPR of more than 0.8 during their first year of therapy.
“Adherence was associated with a significantly lower risk of subsequent osteoporotic fracture among newly treated bisphosphonate users, even after adjusting for numerous potential confounders such as prior fracture, selected comorbidities, concomitant medication use and demographic characteristics,” they wrote. “Specifically, bisphosphonate users who achieved a MPR >0.8 had a 14% lower adjusted fracture risk compared with patients with a MPR <0.5.”
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