Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, Expanded-Access Study

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art_FLESERIU_Safety_and_Efficacy_of_Subcutaneous_Pasireotide_in_Patients_2019.PDF (601.64 KB)
Citações na Scopus
15
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
FLESERIU, Maria
IWEHA, Chioma
MAZZUCO, Tania Longo
CAMPIGOTTO, Federico
MAAMARIS, Ricardo
LIMUMPORNPETCH, Padiporn
Citação
FRONTIERS IN ENDOCRINOLOGY, v.10, article ID 436, 14p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Introduction: The efficacy and safety of subcutaneous (sc) pasireotide have been evaluated in a Phase III trial. Here, we report safety and efficacy results from a multinational, expanded-access study of pasireotide sc in patients with Cushing's disease (CD) in a real-world setting (clinicaltrials. gov, identifier: NCT01582061). Methods: Adults with active CD previously untreated with pasireotide were enrolled; pasireotide sc was initiated at 600 mu g twice daily (bid; EU countries) or 900 mu g bid (non-EU countries; 600 mu g bid in patients with impaired glucosemetabolism). Pasireotide dose could be adjusted in 300 mu g increments/decrements to amaximumof 900 mu g bid or minimum of 300 mu g bid for sustained urinary free cortisol (UFC) normalization/tolerability issues. Primary objective: document the safety of pasireotide sc in patients with CD. Key secondary objectives: assess the proportion of patients with mean UFC (mUFC) not exceeding the upper limit of normal (ULN) and changes from baseline in clinical signs/symptoms and quality of life (QoL) to weeks 12, 24, and 48. Results: One hundred and four patients received pasireotide: female, n = 84 (80.8%); median duration of pasireotide exposure, 25.1 weeks; median (range) baseline mUFC, 321.2 nmol/24 h (142-10,920; 2.3 x ULN [1.0-79.2]). Forty (38.5%) patients completed the study. The most common reasons for premature discontinuation of pasireotide were unsatisfactory therapeutic effect (n = 26, 25.0%) and adverse events (AEs; n = 20, 19.2%). Drug-related grade 3/4 AEs or drug-related serious AEs (primary endpoint) were documented in 42 (40.4%) patients, most commonly diabetes mellitus (n = 12, 11.5%) and hyperglycemia (n = 8, 7.7%). All patients experienced >= 1 AE and most (n = 102; 98.1%) reported >= 1 drug-related AE; six (5.8%) patients discontinued treatment because of hyperglycemia-related AEs. At weeks 12, 24, and 48, respectively, 36/66 (54.5%), 22/46 (47.8%), and 9/21 (42.9%) evaluable patients had normalizedmUFC levels. Clinical signs/symptoms and QoL were also improved. Conclusions: In an international, real-world, clinical-practice setting, pasireotide sc was generally well-tolerated (no new safety signals were identified), effectively reduced UFC (normalization in similar to 50% of evaluable patients) and improved clinical signs and QoL in patients with CD. While hyperglycemia-related AEs were common, consistent with previous studies, most were manageable, with < 6% of patients discontinuing treatment because of these events.
Palavras-chave
Cushing's disease, pasireotide sc, somatostatin analog, clinical practice, real world
URI
https://observatorio.fm.usp.br/handle/OPI/33267
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - ODS/03