Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Denosumab is a RANK ligand antibody and the first biologic agent used for the treatment of post-menopausal osteoporosis (OP) and prevention of bone metastases complications. The aim of this meta-analysis was to assess the safety of Denosumab.
Methods: 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).
Results: 6136 articles were of potential interest, and 19 met the inclusion criteria. 7 articles (3859 patients) 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) and all infections (AI) (RR=1.11, 95% CI=0.98-1.25). Regarding Denosumab versus placebo in post-menopausal OP, 7 studies (8724 patients) 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), AI (RR=1.11, 95% CI=0.98-1.25), however cellulitis was more frequently found with Denosumab (RR=8.03, 95% CI=1.44-4.00). No cases of osteonecrosis of the jaw (ONJ) has 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), AI (RR=1.01, 95% CI=0.89-1.13) 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).
Conclusion: 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; that could be explained by a relative immunosuppression and a higher dose of Denosumab used in these patients. Patients with bone metastases treated with Denosumab tended to have a higher risk of ONJ although not significant.
To cite this abstract in AMA style:Aubailly M, Combe B, Gaujoux-Viala C, Lukas C, Morel J, Che H. Safety of Denosumab in Postmenopausal Osteoporosis and in Cancer and Bone Metastase Treatment: A Systematic Review and Meta-Analysis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/safety-of-denosumab-in-postmenopausal-osteoporosis-and-in-cancer-and-bone-metastase-treatment-a-systematic-review-and-meta-analysis/. Accessed December 1, 2020.
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