FRI0561 Safety of denosumab in post-menopausal osteoporosis and in cancer: a systematic review and meta-analysis
Authors: M Aubailly, T Barnetche, B Combe, C Gaujoux-viala, C Lukas, J Morel, H Che
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Denosumab is a RANK ligand antibody (1) used for the treatment of post-menopausal osteoporosis (OP) and prevention of bone metastases complications (2,3). <h3>Objectives</h3> The aim of this meta-analysis was to assess the safety of Denosumab. <h3>Methods</h3> Data sources included MEDLINE, EMBASE, Cochrane Library, and recent abstracts from ACR and EULAR congresses were searched until March 2016. Randomized controlled trials comparing the safety of Denosumab to placebo or bisphosphonates (BP) in postmenopausal OP and in cancer (either cancer with bone metastases or with hormone therapy) were selected. Data were extracted by one investigator, confirmed by another, and pooled in meta-analysis using Review Manager software (Cochrane collaboration). <h3>Results</h3> 6136 articles were of potential interest, and 19 met the inclusion criteria. 7 articles compared the safety of Denosumab to BP in post-menopausal OP. There was no significant difference when comparing Denosumab with bisphosphonates in any adverse events (AAE) (RR=0.98, 95% CI=0.95–1.01) serious adverse event (SAE) (RR=1.04, 95% CI=0.81–1.33). Regarding Denosumab versus placebo in post-menopausal OP, 7 studies were included and there was no significant difference in AAE (RR=0.98, 95% CI=0.94–1.01), SAE (RR=1.03, 95% CI=0.96–1.11), however cellulitis was more frequently found with Denosumab (RR=8.03, 95% CI=1.44–44.79). No cases of osteonecrosis of the jaw (ONJ) had been reported. 5 articles were pooled to compare Denosumab with BP in patients with bone metastases and no significant difference was found in AAE (RR=0.99, 95% CI=0.98–1.00), SAE (RR=0.99, 95% CI=0.95–1.03), and ONJ (RR=1.40, 95% CI=0.92–2.13). 4 articles were selected concerning patients treated with placebo or Denosumab in breast and prostate cancer without bone metastases. Although no significant difference was found in AAE (RR 1.01, 95% CI=0.99–1.03), use of Denosumab was associated with a significantly increased risk of hypocalcemia (RR 5.20, 95% CI=1.34–20.13) and of cholecystitis (RR 3.43, 95% CI=1.01–11.69). <h3>Conclusions</h3> In post-menopausal OP, Denosumab had a relatively good safety profile although significantly more cellulitis occurred when compared with placebo. For patient with cancer, Denosumab was associated with more hypocalcemia and cholecystitis than placebo. <h3>References</h3> Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–42. Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;24(1):153–61. Lipton A, Fizazi K, Stopeck AT, Henry DH, Smith MR, Shore N, et al. Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Eur J Cancer Oxf Engl 1990. 2016;53:75–83. <h3>Disclosure of Interest</h3> None declared