J Clin Endocrinol Metab. 2020 Jan 3. pii: dgz322. doi: 10.1210/clinem/dgz322. [Epub ahead of print]
Denosumab inhibits the receptor activator of nuclear factor κ-Β ligand, an immune system modulator. Safety endpoints including risk for infections were assessed as secondary outcomes in randomized controlled trials (RCTs) of the drug.
To assess the risk of serious adverse events of infections (SAEI) in denosumab-treated patients.
PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019.
All RCTs of denosumab (60 mg every 6 months) versus any comparator were included. We excluded trials in cancer patients for prevention of skeletal-related events.
Two reviewers independently applied selection criteria and extracted the data. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a fixed effect model. Sensitivity analysis was based on risk of bias.
Thirty-three studies (22,253 patients) were included. There was a higher incidence of SAEI during denosumab treatment versus any comparator (RR, 1.21; 95% CI, 1.04-1.40; I2 = 0%), mainly of ear, nose and throat (RR ,2.66; 95% CI, 1.20-5.91) and gastrointestinal origin (RR, 1.43; 95% CI, 1.02-2.01). Risk ratio was similar in a sensitivity analysis based on adequate allocation concealment. The risk ratio of any infection (RR, 1.03; 95% CI, 0.99-1.06) and infection-related mortality (RR, 0.50; 95% CI, 0.20-1.23) was comparable between groups.
A higher incidence of SAEI is demonstrated during treatment with denosumab in an osteoporosis dose. Nevertheless, the overall risk for any infection or related mortality is similar to comparator groups. These findings merit consideration before therapy initiation.