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Review
. 2024 May-Jun;28(3):232-238.
doi: 10.4103/ijem.ijem_260_23. Epub 2024 Jun 26.

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

Lakshmi Nagendra  1 , Deep Dutta  2 , Nishant Raizada  3 , Vineet Surana  4 , Chitra Selvan  5 , Saptarshi Bhattacharya  6
Affiliations
Review

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

Lakshmi Nagendra et al. Indian J Endocrinol Metab. 2024 May-Jun.

Abstract

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); P < 0.00001; I2 = 0%]. The occurrence of adverse events [OR 1.35 (95% CI: 0.52-3.53); P = 0.54; I2 = 0%; low heterogeneity (LH); High certainty of evidence (HCE)], serious adverse events (SAEs) [OR 1.32 (95% CI: 0.30-5.79); P = 0.72; I2 = 0%; LH; HCE], adrenal insufficiency [OR 5.38 (95% CI: 0.91-31.78); P = 0.06; I2 = 0%; LH; HCE], headache [OR 0.98 (95% CI: 0.35-2.76); P = 0.97; I2 = 0%; LH; HCE], hyperandrogenism [OR 3.68 (95% CI: 0.59-22.80); P = 0.16; I2 = 0%; LH; HCE] and deaths [OR 0.32 (95% CI: 0.01-8.00); P = 0.48; I2 = 0%; LH; HCE] was comparable among the groups. The occurrence of nausea [OR 4.25 (95% CI: 1.26-14.30); P = 0.02; I2 = 0%; LH] and arthralgia [OR 6.54 (95% CI: 1.64-26.13); P = 0.008; I2 = 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.

Keywords: Adrenal; cushing’s disease; cushing’s syndrome; osilodrostat; pituitary.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart elaborating on study retrieval and inclusion in this systematic review. RCT: Randomized controlled trial
Figure 2
Figure 2
(a) Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies; (b) Risk of bias summary: review authors’ judgements about each risk of bias item for each included study
Figure 3
Figure 3
Forest plot highlighting the impact of osilodrostat as compared to the placebo group on (a) Percentage of patients achieving normal 24-h UFC; (b) Total adverse events; (c) Serious adverse events; (d) adrenal insufficiency (e) headache (f) hyperandrogenism (g) deaths (h) nausea
See this image and copyright information in PMC

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