Indirect comparison of bazedoxifene vs oral bisphosphonates for the prevention of vertebral fractures in postmenopausal osteoporotic women

Abstract

Objective:

Compare the efficacy of bazedoxifene with oral bisphosphonates for reduction of vertebral fracture risk in postmenopausal osteoporotic (PMO) women and in higher-risk patients based on evidence from randomized controlled trials (RCTs).

Methods:

Eight RCTs assessing vertebral fracture risk reduction with oral bisphosphonates (n = 7) or bazedoxifene (n = 1) were identified by a systematic literature review. Individual study results were pooled in a network meta-analysis (NMA) to indirectly compare treatment effects for overall PMO women and a higher-risk subgroup (FRAX ≥ 20%). Three sets of NMA analyses were conducted: aggregate data (AD) from the bisphosphonate RCTs and bazedoxifene RCT for the full population or the FRAX ≥20% subgroup (NMA AD); bisphosphonate AD and bazedoxifene AD from each FRAX subgroup adjusted for baseline risk (NMA AD meta-regression); and bisphosphonate AD and bazedoxifene individual patient data (IPD) adjusted for baseline risk/FRAX (NMA AD/IPD meta-regression).

Results:

For the overall population, bisphosphonates had lower fracture risks versus bazedoxifene although there is considerable uncertainty in supporting one intervention over another. The relative risk reduction (RRR) for bazedoxifene was −0.23 (95% CrI: −1.11, 0.27) versus ibandronate, −0.17 (−0.76, 0.22) versus alendronate, and −0.06 (−0.62, 0.30) versus risedronate. Results from the meta-regression analyses were similar. For the FRAX ≥20% population, estimated fracture rates with bazedoxifene were lower than with bisphosphonates, but again the uncertainty limits strong interpretation. The RRR for bazedoxifene was 0.51 (−0.31, 0.83) versus ibandronate, 0.53 (−0.18, 0.83) versus alendronate, and 0.57 (−0.07, 0.85) versus risedronate. The meta-regression analyses showed comparable findings.

Conclusion:

The analyses only considered vertebral fractures for oral bisphosphonates versus bazedoxifene, and IPD was available only for bazedoxifene. In light of this, bazedoxifene is comparable to bisphosphonates in the overall PMO population and at least as effective as bisphosphonates for preventing vertebral fractures among higher-risk PMO patients. The findings suggest bazedoxifene performs better in higher-risk PMO than in the overall PMO.

Keywords::

• Bazedoxifene
• Bisphosphonates
• Fractures
• Indirect comparison
• Osteoporosis

Transparency

Declaration of funding

This study was sponsored by Pfizer Inc.

Declaration of financial/other relationships

A.G.E. and J.P.J. have disclosed that they are former employees of Mapi, who were paid consultants by Pfizer in connection with the development of this manuscript. The systematic review and network meta-analysis were performed at Mapi, and Mapi is also responsible for the data storage. J.-Y.R. has disclosed that he is a recipient of consulting and advisory board fees from Servier, Novartis, Negma, Eli Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merck, Nycomed, NPS, Theramex and UCB. He has received fees for speaking at invited lectures from Merck Sharp and Dohme, Elli Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk and Nolver, and has received grant support from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Eli Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, and Servier. X.L., A.B., R.W., and S.M. have disclosed that they are employees of Pfizer. S.S. has disclosed that he is a former employee of Pfizer.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.