Risk for Infections During Treatment With Denosumab for Osteoporosis: A Systematic Review and Meta-analysis
Talia Diker-Cohen1,2,3, Dana Rosenberg1,3, Tomer Avni1,3
1Medicine A.
Context:
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.
Objective:
To assess the risk of serious adverse events of infections (SAEI) in denosumab-treated patients.
Data Sources:
PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019.
Study Selection:
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.
Data Extraction:
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.
Data Synthesis:
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). RR was similar in a sensitivity analysis based on adequate allocation concealment. The RR 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.
Conclusions:
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.
Insights
Denosumab treatment shows a higher risk of serious adverse events of infections (SAEI), particularly in the ear, nose, throat, and gastrointestinal areas. However, the overall risk for any infection or related mortality remains comparable to control groups.
Area of Science:
- Immunology and Pharmacology
- Clinical Trials and Evidence Synthesis
Background:
- Denosumab is a biologic agent that modulates the immune system by inhibiting the receptor activator of nuclear factor κ-Β ligand (RANKL).
- Safety endpoints, including infection risk, are crucial secondary outcomes in randomized controlled trials (RCTs) evaluating denosumab.
- Understanding the infection risk associated with denosumab is essential for clinical decision-making.
Purpose of the Study:
- To systematically assess the risk of serious adverse events of infections (SAEI) in patients treated with denosumab.
- To quantify the incidence of specific types of infections associated with denosumab therapy.
- To compare the overall risk of infection and infection-related mortality between denosumab and comparator groups.
Main Methods:
- A comprehensive literature search was conducted in PubMed and the Cochrane Central Register of Controlled Trials up to May 27, 2019.
- Included were all RCTs of denosumab (60 mg every 6 months) excluding trials for cancer-related skeletal events.
- Data extraction and risk ratio (RR) pooling were performed by two independent reviewers using a fixed-effect model, with sensitivity analysis based on risk of bias.
Main Results:
- Thirty-three RCTs comprising 22,253 patients were analyzed.
- Denosumab treatment was associated with a higher incidence of SAEI (RR, 1.21; 95% CI, 1.04-1.40), predominantly 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).
- The overall risk for any infection (RR, 1.03; 95% CI, 0.99-1.06) and infection-related mortality (RR, 0.50; 95% CI, 0.20-1.23) did not differ significantly between groups.
Conclusions:
- Denosumab, at osteoporosis dosing, is associated with an increased incidence of serious adverse events of infections.
- Despite the increased risk of SAEI, the overall risk of any infection and infection-related mortality remains comparable to control treatments.
- These findings necessitate careful consideration of infection risk prior to initiating denosumab therapy.
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