Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial

• Published in: The Lancet (British edition) 2015-09, Vol.386 (9999), p.1147-1155
• Main Authors: Leder, Benjamin Z, Dr, Tsai, Joy N, MD, Uihlein, Alexander V, MD, Wallace, Paul M, BA, Lee, Hang, PhD, Neer, Robert M, MD, Burnett-Bowie, Sherri-Ann M, MD
• Format: Article
• Language: English
• Subjects: Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Bone density; Bone Density - drug effects; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Bone mineral density; Clinical trials; Denosumab; Drug Administration Schedule; Drug Substitution; Drug therapy; Drug Therapy, Combination; Female; Follow-Up Studies; Fractures; Humans; Internal Medicine; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - physiopathology; Single-Blind Method; Spine; Teriparatide - administration & dosage; Teriparatide - adverse effects; Teriparatide - therapeutic use; Variance analysis; Womens health
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(15)61120-5

Summary Background Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments. Methods This randomised controlled trial (DATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA), in which 94 postmenopausal osteoporotic women were randomly assigned to receive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs. In DATA-Switch, women originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally assigned to both received an additional 24 months of denosumab alone (combination to denosumab group). Bone mineral density at the spine, hip, and wrist were measured 6 months, 12 months, 18 months, and 24 months after the drug transitions as were biochemical markers of bone turnover. The primary endpoint was the percent change in posterior-anterior spine bone mineral density over 4 years. Between-group changes were assessed by one-way analysis of variance in our modified intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00926380. Findings Between Sept 27, 2011, and Jan 28, 2013, eligible women from the DATA study were enrolled into DATA-Switch. Of 83 potential enrollees from the DATA study, 77 completed at least one post-baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18·3% (95% CI 14·9–21·8) in 27 women in the teriparatide to denosumab group, 14·0% (10·9–17·2) in 27 women the denosumab to teriparatide group, and 16·0% (14·0–18·0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between-group comparison