Effectiveness of Medical treatment of Cushing’s disease: systematic review and meta- analysis

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  • Presentation type: Pôster
  • Track: 2. Metodologia e resultados de estudos de ATS
  • Keywords: Cushing's disease; pasireotide; cabergoline; ketoconazole; systematic review;
  • 1 Institute of health economics and Clinical Epidemiology - University of Cologne
  • 2 Universidade Federal de Minas Gerais
  • 3 Universidade Federal do Paraná
  • 4 Weill Cornell Medicine
  • 5 Faculdade de Medicina de Botucatu - Universidade Estadual Paulista- UNESP-

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Introduction: Pasireotide, cabergoline and ketoconazole are commonly used in the treatment of Cushing’s disease (CD). In this context, a systematic review was made with the objective of evaluating the effectiveness and safety of ketoconazole, pasireotide and cabergoline as monotherapy for patients who did not achieve disease control after transsphenoidal surgery (TSS) or who had contraindications to surgery as first-line therapy.
Methods: Randomized and non-randomized controlled trials and non-controlled studies were included. General and adaptive search strategies were created for the Embase, Medline, LILACS, and CENTRAL databases. The primary outcomes were frequency of disease remission, adverse events (AE), reduction of UFC, quality of life and comorbidities related to CD. Two independent reviewers assessed eligibility of the studies, extracted data, and evaluated their risk of bias. Continuous data (pre- and postintervention) were expressed as means and standard deviation (SD), and the standardized mean difference (SMD) were calculated with respective 95% confidence interval (CI). Proportional meta-analyses were performed for the frequency of disease remission and AE.
Results: Nineteen studies were included, three were randomized, but only one compared two different treatments. The frequency of disease control was of 35% for cabergoline (95% CI: 27%, 43%, 7 studies, 177 participants, I 2 : 14%), 36% for pasireotide (95% CI: 25%, 47%, 6 studies, 451 participants, I 2 : 84%) and 46% for ketoconazole (95% CI: 41%, 51%, 4 studies, 401 participants, , I 2 : 0%). The most frequent AEs and with no statistic heterogeneity on proportional meta-analyses were transaminase increase with ketoconazole 14% (95% CI: 10%, 19%, 4 studies, 298 participants, I 2 :0%), diabetes mellitus and fatigue with Pasireotide (18%, 95% CI: 14%, 22%, 6 studies, 502 participants, I 2 :18,6%; and 20%, 95% CI: 16%, 25%, 4 studies, 363 participants, I 2 : 0%, respectively). With very low certainty of evidence, the meta-analyses on UFC improvement favored cabergoline (1.78 SD, 95% CI -3.26,-0.30, 5 studies, 88 participants, I 2 :92%), pasireotide (0.94 SD (95% CI :-1.17, -0.71, 7 studies, 538 participants, I 2 :51%) and ketoconazole (0.6 SD, 95% CI: -0.82,-0.38, 2 studies, 168 participants, I 2 :0%).
Conclusion: Similar treatment effects on disease control were achieved with cabergoline (27-43%), pasireotide (25-47%) and ketoconazole (41-51%). The choice of medical treatment will also be determined by the frequency of adverse events associated with the medical options.

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