Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women

Abstract

The final analysis of this 2-year, randomized, crossover study showed that postmenopausal women with osteoporosis were more adherent, compliant, and persistent with subcutaneous denosumab injections every 6 months than with once-weekly alendronate tablets. After receiving both treatments, women reported greater satisfaction with injectable denosumab and preferred it over oral alendronate.

Introduction: Osteoporosis patients who are non-compliant or non-persistent with therapy may have suboptimal clinical outcomes. This 2-year, randomized, open-label, crossover study compared treatment adherence between subcutaneous denosumab, 60 mg every 6 months, and oral alendronate, 70 mg once weekly.

Methods: Postmenopausal women at 25 centers in the USA and Canada with bone mineral density T-scores -4.0 to -2.0 and no prior bisphosphonate use received alendronate then denosumab, or denosumab then alendronate, over successive 12-month periods. Adherence required both compliance (denosumab injections 6 months apart or ≥ 80% of alendronate tablets) and persistence (both denosumab injections or ≥ 2 alendronate doses in the last month and completion of the treatment period).

Results: Of the 250 women enrolled (124 alendronate, 126 denosumab), 221 entered the second year (106 denosumab, 115 alendronate). Denosumab was associated with less non-adherence than alendronate (first year, 11.9% vs 23.4%; second year, 7.5% vs 36.5%). Risk ratios for non-adherence, non-compliance, and non-persistence favored denosumab in both years (p < 0.05). Of 198 subjects expressing treatment preference, 183 (92.4%) preferred the injections over the oral therapy. BMD improved further when subjects received denosumab after alendronate and remained stable when they received alendronate after denosumab.

Conclusion: Based on the final results of this crossover study after women had received each treatment for up to 1 year, postmenopausal women with osteoporosis were more adherent, compliant, and persistent with subcutaneous denosumab injections every 6 months than with once-weekly alendronate tablets and reported increased treatment preference and satisfaction with injectable denosumab over oral alendronate.

Trial registration: ClinicalTrials.gov NCT00518531.

Figures

Fig. 1

Subject disposition. Note: One subject received both study treatments in a single period and was considered to have received denosumab for safety analyses in that period. The safety population included all subjects who received at least one dose of study medication; subjects in the alendronate group were required to return at least one MEMS bottle to confirm they had received at least one dose of alendronate. Subjects were considered to have completed the period/year if the year's month 12 visit occurred within or later than the schedule visit window with “Yes” for the end-of-year completion response

Fig. 2

Time to treatment non-adherence. Non-adherence to alendronate could begin at any time, and the time to non-adherence was defined as the time to treatment non-compliance or time to treatment non-persistence, whichever occurred earliest. The time to denosumab non-adherence for non-adherent subjects was defined as 6 months and 4 weeks after the most recent injection. For each treatment group, time points with >95% cumulated subjects were excluded

Fig. 3

Mean scores on the BMQ. *p < 0.05 between treatment groups. †p < 0.05 between treatment groups for difference in change score from each year's baseline. ‡n values are shown for the number of subjects with observed data in the first and second years, respectively; the latter population was used for the analysis of scores at the crossover visit. §Visit 1 baseline; visit 2 year 1, month 6; visit 3 crossover (BMQ baseline of year 2 treatment); visit 4 year 2, month 6; visit 5 year 2, month 12. Total score ranged from 1 to 5. Higher scores indicate stronger beliefs, concerns, and preference

Fig. 4

Subject-reported satisfaction with alendronate or denosumab at the end of the study. *Alendronate/denosumab group (ALN/DMAB): data were from the last measurements of the first year for alendronate and the last measurements of the second year for denosumab. †Denosumab/alendronate group (DMAB/ALN): data were from the last measurements of the first year for denosumab and the last measurements of the second year for alendronate. ‡Combined: includes combined data from both groups