Risk of psychiatric disorders and all-cause mortality with belimumab therapy in patients with systemic lupus erythematosus: a meta-analysis of randomised controlled trials

Objectives To evaluate the risk of psychiatric disorders and all-cause mortality associated with belimumab therapy in patients with SLE. Methods A literature search of four electronic bibliographic databases, including PubMed, EMBASE, Scopus and Cochrane databases, was conducted for randomised controlled trials (RCTs) reporting adverse reactions between belimumab and placebo. OR and 95% CI were calculated using the Mantel-Haenszel method with fixed-effects or random-effects model, depending on the heterogeneity test. Results In total, 11 eligible RCTs including 8824 patients with SLE were randomised into belimumab (5160 patients with 5552 patient-years) and placebo (3664 patients with 3985 patient-years) groups, respectively. Overall, no increased risk was identified with belimumab therapy at all dosages compared with placebo in patients with SLE regarding all psychiatric disorders (OR 0.89, 95% CI 0.64 to 1.23, I-2=58%) and all-cause mortality (OR 1.10, 95% CI 0.64 to 1.89, I-2=0%). The subgroup analysis of psychiatric disorders also revealed no statistically elevated risks in serious psychiatric disorders (OR 1.15, 95% CI 0.77 to 1.70, I-2=47%), non-serious psychiatric disorders (OR 0.83, 95% CI 0.60 to 1.16, I-2=52%), suicidal ideation or behaviour (OR 0.87, 95% CI 0.57 to 1.33, I-2=0%), and depression (OR 1.29, 95% CI 0.90 to 1.85, I-2=15%). Secondary analysis restricting belimumab at approved dose of 10 mg/kg only yielded similar results. Conclusion Belimumab therapy overall does not increase psychiatric events and all-cause mortality risks, whereas the results from Belimumab Assessment of Safety in SLE Study are suggestive of increased risk of psychiatric adverse events with belimumab exposure. Consequently, post-marketing data are needed to ascertain its psychiatric safety, especially serious mental disorders.