AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double-blind, efficacy, and safety study.
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
24
07
2023
received:
12
06
2023
accepted:
11
08
2023
pubmed:
24
10
2023
medline:
24
10
2023
entrez:
24
10
2023
Statut:
ppublish
Résumé
Oral corticosteroid use is limited by side effects, some caused by off-target actions on the mineralocorticoid receptor that disrupt electrolyte balance. AZD9567 is a selective, nonsteroidal glucocorticoid receptor modulator. The efficacy, safety, and tolerability of AZD9567 and prednisolone were assessed in a phase IIa study. Anti-inflammatory mechanism of action was also evaluated in vitro in monocytes from healthy donors. In this randomized, double-blind, parallel-group, multicenter study, patients with active rheumatoid arthritis were randomized 1:1 to AZD9567 40 mg or prednisolone 20 mg once daily orally for 14 days. The primary end point was change from baseline in DAS28-CRP at day 15. Secondary end points included components of DAS28-CRP, American College of Rheumatology (ACR) response criteria (ACR20, ACR50, and ACR70), and safety end points, including serum electrolytes. Overall, 21 patients were randomized to AZD9567 (n = 11) or prednisolone (n = 10), and all completed the study. As anticipated, AZD9567 had a similar efficacy profile to prednisolone, with no clinically meaningful (i.e., >1.0) difference in change from baseline to day 15 in DAS28-CRP between AZD9567 and prednisolone (least-squares mean difference: 0.47, 95% confidence interval: -0.49 to 1.43). Similar results were observed for the secondary efficacy end points. In vitro transcriptomic analysis showed that anti-inflammatory responses were similar for AZD9567, prednisolone, and dexamethasone. Unlike prednisolone, AZD9567 had no effect on the serum sodium:potassium ratio. The safety profile was not different from that of prednisolone. Larger studies of longer duration are required to determine whether AZD9567 40 mg may in the future be an alternative to prednisolone in patients with inflammatory disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2494-2506Investigateurs
J W G Jacobs
(JWG)
Ellen Kaan
(E)
Astrid van Tubergen
(A)
Kasper Hermans
(K)
Harald Vonkeman
(H)
Marjan Ghiti Moghadam
(MG)
Inger Gjertsson
(I)
Anna-Karin Ekwall
(AK)
Meliha Kapetanovic
(M)
Jon Thorkell Einarsson
(JT)
Lena T Axelsson
(LT)
Richard Olsson
(R)
Tove Hegelund Myrbäck
(TH)
Ziad Taib
(Z)
Kerstin Vikman
(K)
Informations de copyright
© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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