Analysis of the Comparative Effectiveness of 3 Oral Bisphosphonates in a Large Managed Care Organization: Adherence, Fracture Rates, and All-Cause Cost

BACKGROUND: Despite widespread availability and use of oral bisphosphonates, fracture rates and associated medical costs are still high. Differences in fracture risk among these agents, if any, have not been quantified due to the lack of high-quality, head-to-head, randomized, controlled trials assessing this outcome. Randomized, placebo-controlled trials have shown that alendronate and risedronate reduce rates of both vertebral and nonvertebral fractures, whereas only reduction in vertebral fractures has been found for ibandronate. OBJECTIVES: To determine if there were any differences among 3 oral bisphosphonates in adherence, total cost of care, and effectiveness in reducing fracture rates in a large managed care population. METHODS: Administrative, longitudinal pharmacy and medical claims data were obtained from 14 geographically diverse health plans in the United States covering approximately 14 million members. Sampled membershad at least 1 pharmacy claim for alendronate, risedronate, or ibandronate during the intake period (January 1, 2005, through October 31, 2007). The date of the first pharmacy claim for osteoporosis medications within the intake period was the index date. Members were followed for either 12, 24, or 36 months, depending on length of continuous health plan eligibility. Medication possession ratio (MPR) was measured using a total days supply that was calculated by multiplying the total quantity dispensed by the suggested days supply per unit of dispensing based on manufacturer-recommended dosing. For members who switched bisphosphonate strengths or medications, the estimated days supply was summed for all osteoporosis medications during the follow-up, including overlapping days supply. Outcomes included (a) the first incident fracture and percentages of members with at least 1 fracture after 6 months post-index; (b) the number of days from index to the first incident fracture, measured as time to event in Cox proportional hazards regression analysis; and (c) total all-cause health care costs (health plan allowed amount including member cost share). RESULTS: A total of 45,939 members were included (n=24,909 alendronate, n=13,834 risedronate, n=7,196 ibandronate). In the 12-month analysis, MPRs were comparable (means=0.57-0.58) for the 3 medications. After 24 months, MPRs had dropped for all medications, but those of both alendronate (mean=0.50, 95% CI=0.49-0.50) and risedronate (mean=0.50, 95% CI=0.49-0.51) were slightly higher than that of ibandronate (mean=0.47, 95% CI=0.46-0.48). At 36 months, again the MPRs had dropped for all 3 medications (means=0.44-0.47) but were similar. There were no statistically significant differences among agents in the percentages of subjects with at least 1 fracture at 12, 24, or 36 months (36-month rates: alendronate 4.41%, risedronate 4.38%, ibandronate 6.28%, P = 0.102). The numbers of subjects with fracture(s) per month of follow-up were 0.0020 for alendronate, 0.0021 for risedronate, and 0.0022 for ibandronate (P=0.087 overall). However, after adjusting for member characteristics, alendronate users had a 12% lower risk of experiencing any incident fracture than ibandronate users (hazard ratio=0.88, 95% CI=0.78-0.99, P = 0.034) within the follow-up period. In the first 12 post-index months, ibandronate users had higher mean [SD] unadjusted total all-cause health care costs ($7,464 [$15,975]) compared with alendronate ($7,233 [$16,671]) and risedronate ($ 6,983 [$16,870], P less than 0.001 for both comparisons), differences of approximately $19 per month and $40 per month, respectively. The results of the unadjusted 24-month analysis were similar, but there were no significant cost differences at 36 months. Total cost differences for the 3 medication groups were nonsignificant at 12, 24, and 36 months after adjusting for member characteristics. CONCLUSIONS: This retrospective analysis of an administrative claims database in a large managed care population showed similar rates of adherence and total adjusted all-cause health care costs for alendronate, risedronate, and ibandronate. Absolute unadjusted rates of fracture were small and did not significantly differ among agents, but after controlling for differences in member characteristics, the risk of fracture was 12% lower for alendronate users than for ibandronate users.