Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis
ObjectiveThe objective of this systematic review was to evaluate the effectiveness and safety of pasireotide, cabergoline, ketoconazole, levoketoconazole, metyrapone, osilodrostat, and temozolomide for the treatment of Cushing’s disease (CD).MethodsThe primary outcomes were the proportion of CD cont...
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doaj-dd38356d566649018c089b4130b1b6ed2021-09-17T13:31:17ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-09-011210.3389/fendo.2021.732240732240Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-AnalysisJulia Simões Corrêa Galendi0Afonso Nogueira Simões Correa Neto1Michelle Demetres2Cesar Luiz Boguszewski3Vania dos Santos Nunes Nogueira4University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Health Economics and Clinical Epidemiology, Cologne, GermanyMedical School, Federal University of Minas Gerais, Belo Horizonte, BrazilSamuel J. Wood Library & C.V. Starr Biomedical Information Center, Weill Cornell Medicine, New York, NY, United StatesDepartment of Internal Medicine, Endocrine Division (SEMPR), Federal University of Parana, Curitiba, BrazilDepartment of Internal Medicine, São Paulo State University/UNESP, Medical School, Botucatu, São Paulo, BrazilObjectiveThe objective of this systematic review was to evaluate the effectiveness and safety of pasireotide, cabergoline, ketoconazole, levoketoconazole, metyrapone, osilodrostat, and temozolomide for the treatment of Cushing’s disease (CD).MethodsThe primary outcomes were the proportion of CD control, adverse events (AE), and reduction of urinary free cortisol. Search strategies were applied to Embase, Medline, and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Standardized mean difference was calculated with 95% confidence interval (CI) for continuous data (i.e., pre- and post-intervention). Random meta-analyses for the proportion of CD control and AE were conducted.ResultsTwenty-nine controlled and non-controlled studies were included. No study with temozolomide and levoketoconazole and one study with osilodrostat fulfilled the inclusion criteria. The meta-analyses of proportion of CD control was 35% for cabergoline (95% CI: 27–43%, six studies, 141 participants), 44% for pasireotide (95% CI: 25–35%, eight studies, 522 participants), 41% for ketoconazole (95% CI: 36–46%, six studies, 450 participants), 66% for metyrapone (95% CI: 46–87%, four studies, 66 participants), and of 66.4% for osilodrostat (95% CI: 57.9, 74.3, 97 participants, one study). One study compared two different treatments (cabergoline vs. ketoconazole), and no statistical difference was observed in CD control (RR: 0.53, 95% CI: 0.15 to 1.87, 14 participants, very low certainty of evidence). The most frequent AE associated with pasireotide was hyperglycemia, dizziness and nausea with cabergoline and metyrapone, and elevated transaminases with ketoconazole.ConclusionThe superiority of one drug over another could not be determined due to lack of controlled studies, but the proportion of disease control identified in our meta-analysis may support clinical decision. New therapeutic options should be investigated due to the limited efficacy and tolerability of the currently available medical treatment for patients with Cushing’s disease.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567.https://www.frontiersin.org/articles/10.3389/fendo.2021.732240/fullCushing’s diseasepasireotide (SOM230)cabergolineketoconazolemetyraponesystematic literature review |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Simões Corrêa Galendi Afonso Nogueira Simões Correa Neto Michelle Demetres Cesar Luiz Boguszewski Vania dos Santos Nunes Nogueira |
spellingShingle |
Julia Simões Corrêa Galendi Afonso Nogueira Simões Correa Neto Michelle Demetres Cesar Luiz Boguszewski Vania dos Santos Nunes Nogueira Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis Frontiers in Endocrinology Cushing’s disease pasireotide (SOM230) cabergoline ketoconazole metyrapone systematic literature review |
author_facet |
Julia Simões Corrêa Galendi Afonso Nogueira Simões Correa Neto Michelle Demetres Cesar Luiz Boguszewski Vania dos Santos Nunes Nogueira |
author_sort |
Julia Simões Corrêa Galendi |
title |
Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis |
title_short |
Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis |
title_full |
Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis |
title_fullStr |
Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis |
title_full_unstemmed |
Effectiveness of Medical Treatment of Cushing’s Disease: A Systematic Review and Meta-Analysis |
title_sort |
effectiveness of medical treatment of cushing’s disease: a systematic review and meta-analysis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2021-09-01 |
description |
ObjectiveThe objective of this systematic review was to evaluate the effectiveness and safety of pasireotide, cabergoline, ketoconazole, levoketoconazole, metyrapone, osilodrostat, and temozolomide for the treatment of Cushing’s disease (CD).MethodsThe primary outcomes were the proportion of CD control, adverse events (AE), and reduction of urinary free cortisol. Search strategies were applied to Embase, Medline, and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Standardized mean difference was calculated with 95% confidence interval (CI) for continuous data (i.e., pre- and post-intervention). Random meta-analyses for the proportion of CD control and AE were conducted.ResultsTwenty-nine controlled and non-controlled studies were included. No study with temozolomide and levoketoconazole and one study with osilodrostat fulfilled the inclusion criteria. The meta-analyses of proportion of CD control was 35% for cabergoline (95% CI: 27–43%, six studies, 141 participants), 44% for pasireotide (95% CI: 25–35%, eight studies, 522 participants), 41% for ketoconazole (95% CI: 36–46%, six studies, 450 participants), 66% for metyrapone (95% CI: 46–87%, four studies, 66 participants), and of 66.4% for osilodrostat (95% CI: 57.9, 74.3, 97 participants, one study). One study compared two different treatments (cabergoline vs. ketoconazole), and no statistical difference was observed in CD control (RR: 0.53, 95% CI: 0.15 to 1.87, 14 participants, very low certainty of evidence). The most frequent AE associated with pasireotide was hyperglycemia, dizziness and nausea with cabergoline and metyrapone, and elevated transaminases with ketoconazole.ConclusionThe superiority of one drug over another could not be determined due to lack of controlled studies, but the proportion of disease control identified in our meta-analysis may support clinical decision. New therapeutic options should be investigated due to the limited efficacy and tolerability of the currently available medical treatment for patients with Cushing’s disease.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567. |
topic |
Cushing’s disease pasireotide (SOM230) cabergoline ketoconazole metyrapone systematic literature review |
url |
https://www.frontiersin.org/articles/10.3389/fendo.2021.732240/full |
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