Efficacy and Safety of Osilodrostat in Managing Cushing's Syndrome: A Systematic Review and Meta-Analysis.

No meta-analysis has holistically analysed and summarized the efficacy and safety of osilodrostat, a novel dual 11β-hydroxylase (cytochrome P450 family 11 subfamily B member 1 [CYP11B1]) and 18-hydroxylase (aldosterone synthase, CYP11B2) inhibitor in managing Cushing's syndrome (CS). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for randomized controlled trials (RCTs) involving patients with CS receiving osilodrostat in the intervention arm. The primary outcome was to evaluate changes in urine free cortisol (UFC) levels. Secondary outcomes were to evaluate alterations in cortisol levels, androgen levels, mineralocorticoid levels, and adverse events. From initially screened 109 articles, data from 2 RCTs involving 144 patients was analysed. After 8-12 weeks of therapy, the odds of achieving a normal 24-hour UFC was higher in patients receiving oslidrostat as compared to placebo. [odds ratio (OR) 21.94 (95% CI: 8.53-56.43); < 0.00001; I = 0%]. The occurrence of adverse events [OR 1.35 (95% CI: 0.52-3.53); = 0.54; I = 0%; low heterogeneity (LH); High certainty of evidence (HCE)], serious adverse events (SAEs) [OR 1.32 (95% CI: 0.30-5.79); = 0.72; I = 0%; LH; HCE], adrenal insufficiency [OR 5.38 (95% CI: 0.91-31.78); = 0.06; I = 0%; LH; HCE], headache [OR 0.98 (95% CI: 0.35-2.76); = 0.97; I = 0%; LH; HCE], hyperandrogenism [OR 3.68 (95% CI: 0.59-22.80); = 0.16; I = 0%; LH; HCE] and deaths [OR 0.32 (95% CI: 0.01-8.00); = 0.48; I = 0%; LH; HCE] was comparable among the groups. The occurrence of nausea [OR 4.25 (95% CI: 1.26-14.30); = 0.02; I = 0%; LH] and arthralgia [OR 6.54 (95% CI: 1.64-26.13); = 0.008; I = 0%; LH; HCE] was significantly higher in the osilodrostat group as compared to placebo. Osilodrostat has good efficacy and safety in CS and was well tolerated over 48 weeks of use.