Safety and efficacy of denosumab in osteoporotic patients previously treated with other medications: a systematic review and meta-analysis

ABSTRACT

Introduction: Denosumab is a monoclonal antibody that received approval by the FDA for the treatment of osteoporosis in 2010. Available higher level research evidence concerns the treatment of patients that have not received any anti-osteoporotic medication in the past. Further investigation is warranted, since clinicians often face the challenge of administering the most efficacious drug in patients, pretreated with other medications.

Areas covered: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of denosumab compared to other active anti-osteoporotic agents in patients formerly receiving other treatments. We searched MEDLINE, EMBASE, CENTRAL, the metaRegister of Controlled Trials (mRCT) and clinicaltrials.gov up to April 2017 to identify eligible trials in patients with primary osteoporosis.

Expert opinion: Our meta-analysis included 6 Randomised Controlled Trials encompassing 2968 patients formerly treated with anti-osteoporotic medications. Quantitative data synthesis demonstrated superiority of denosumab in augmenting Bone Mineral Density in all skeletal sites studied compared to controls [treatment difference in total hip: 1.59% (95% CI 1.01, 2.17)], whereas the overall incidence of serious adverse events was not increased (OR 1.12, 95% CI 0.85 to 1.47, p = 0.42). Future research geared towards the fracture incidence, quality of life and patient reported outcomes is warranted.

KEYWORDS:

• Denosumab
• antiosteoporotic medications
• monoclonal antibody
• meta-analysis
• drug safety
• systematic review
• primary osteoporosis
• non-naïve

Article highlights

• There is lack of higher level evidence regarding the efficacy and safety of denosumab in individuals formerly treated with other anti-osteoporotic medications.

• Authors conducted a systematic review and meta-analysis of trials including patients with primary osteoporosis to define the effect of denosumab in increasing BMD and the risk of serious adverse events.

• Altogether 6 RCTs encompassing 2968 patients met the eligibility criteria and were included in the meta-analysis.

• Quantitative data synthesis showed significant increase in BMD gains with the administration of denosumab, in all skeletal sites studied, whereas the occurrence of serious adverse events was not increased.

• No difference in the incidence of clinical fractures was noted, however neither of the 6 studies included was statistically powered to investigate fracture endpoints.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper has not been funded.