Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing's disease: interim results from a long-term real-world evidence study

Luca Manetti, Timo Deutschbein, Jochen Schopohl, Kevin C J Yuen, Michael Roughton, Ulrike Kriemler-Krahn, Libuse Tauchmanova, Ricardo Maamari, Carla Giordano, Luca Manetti, Timo Deutschbein, Jochen Schopohl, Kevin C J Yuen, Michael Roughton, Ulrike Kriemler-Krahn, Libuse Tauchmanova, Ricardo Maamari, Carla Giordano

Abstract

Purpose: Clinical trials have demonstrated the favorable efficacy/safety profile of pasireotide in patients with Cushing's disease (CD). We report interim long-term results of an ongoing real-world evidence study of subcutaneous pasireotide in patients with CD.

Methods: Adults with CD receiving pasireotide, initiated before (prior-use) or at study entry (new-use), were monitored for ≤ 3 years during a multicenter observational study ( https://ichgcp.net/clinical-trials-registry/NCT02310269" title="See in ClinicalTrials.gov">NCT02310269). Primary objective was to assess long-term safety of pasireotide alone or with other CD therapies.

Results: At the time of this interim analysis, 127 patients had received pasireotide (new-use, n = 31; prior-use, n = 96). Eight patients had completed the 3-year observation period, 53 were ongoing, and 66 had discontinued. Among 31 new-use and 92 prior-use patients with ≥ 1 safety assessment, respectively: 24 (77%) and 37 (40%) had drug-related adverse events (AEs); 7 (23%) and 10 (11%) had serious drug-related AEs. Most common drug-related AEs were nausea (14%), hyperglycemia (11%) and diarrhea (11%); these were more frequently reported in new users and mostly of mild-to-moderate severity. 14 (45%) new-use and 15 (16%) prior-use patients experienced hyperglycemia-related AEs. Mean urinary free cortisol (mUFC) was within normal range at baseline and months 1, 12 and 24, respectively, in: 1/16 (6%), 9/18 (50%), 1/3 (33%) and 0/0 new users; 28/43 (65%), 15/27 (56%), 27/33 (82%) and 12/19 (63%) prior users.

Conclusions: Pasireotide is well tolerated and provides sustained reductions in mUFC during real-world treatment of CD. The lower rate of hyperglycemia-related AEs in prior users suggests that hyperglycemia tends not to deteriorate if effectively managed soon after onset.

Clinical trial registration number: NCT02310269.

Keywords: Cushing’s disease; Hypercortisolism; Pasireotide; Pituitary; Safety.

Conflict of interest statement

LM has served on Advisory Boards for Novartis. TD has received Honoraria and Research Grants from, served on Advisory Boards for, and acted as a Consultant for Novartis. KCJY has received Research Grants from Corcept Therapeutics and Novartis and served on Advisory Boards and acted as a Consultant for Corcept Therapeutics, Novartis, and Strongbridge. UKK, LT, MR, and RM are employees of Novartis. CG has received Research Grants from and served on Advisory Boards for Novartis. JS has received Lecture Fees from Novartis, Ipsen, and Pfizer and has served on Advisory Boards for Novartis and Ipsen.

Figures

Fig. 1
Fig. 1
Study design. Patients discontinuing prematurely were followed up for 3 months after the last dose. EOT end of treatment, sc subcutaneous
Fig. 2
Fig. 2
Patient disposition
Fig. 3
Fig. 3
Proportion of patients with mUFC ≤ ULN. Numbers beneath the graph show number of evaluable patients with mUFC ≤ ULN

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Source: PubMed

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