Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
22
02
2023
received:
22
02
2023
accepted:
14
03
2023
medline:
31
8
2023
pubmed:
26
4
2023
entrez:
26
4
2023
Statut:
ppublish
Résumé
This phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc). A multinational double-blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST). The primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 (P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was -6.7 versus -8.1 (P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decline in forced vital capacity in patients on background mycophenolate and those who were taking IST for ≤1 year. No deaths or excess in serious or severe adverse events related to lenabasum were observed. A benefit of lenabasum in dcSSc was not demonstrated. Most patients were treated with background IST, and treatment with mycophenolate mofetil in particular was associated with better outcomes. These findings support the use of IST in the treatment of dcSSc and highlight the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as to clinical care.
Substances chimiques
lenabasum
OGN7X90BT8
Cannabinoid Receptor Agonists
0
Dronabinol
7J8897W37S
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase III
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1608-1618Investigateurs
Arthur Kavanaugh
(A)
Daniel E Furst
(DE)
Suzanne Kafaja
(S)
Lorinda Chung
(L)
Aryeh Fischer
(A)
Virginia Steen
(V)
John Varga
(J)
Lesley Saketkoo
(L)
Laura Hummers
(L)
Flavia V Castelino
(FV)
Robert Simms
(R)
Vivek Nagaraja
(V)
Jerry Molitor
(J)
Nicole M Orzechowski
(NM)
Vivien M Hsu
(VM)
Elana J Bernstein
(EJ)
Robert Spiera
(R)
Jessica Gordon
(J)
Soumya Chatterjee
(S)
Bashar Kahaleh
(B)
Nora Sandorfi
(N)
Robyn T Domsic
(RT)
Edwin Smith
(E)
Zoran Kurepa
(Z)
Maureen Mayes
(M)
Tracy Frech
(T)
Mary Ellen Csuka
(ME)
Susanna Proudman
(S)
Vivek Thakkar
(V)
Wendy Stevens
(W)
Peter Youssef
(P)
Murray Baron
(M)
David Robinson
(D)
Claudia Kedor
(C)
Jörg Distler
(J)
Stephanie Finzel
(S)
Pia Moinzadeh
(P)
Ramona König
(R)
Christiane Pfeiffer
(C)
Norbert Blank
(N)
Alexandra Balbir-Gurman
(A)
Itzhak Rosner
(I)
Yair Levy
(Y)
Merav Lidar
(M)
Eun Bong Lee
(EB)
Chang Keun Lee
(CK)
Jae-Bum Jun
(JB)
Ji Hyeon Ju
(JH)
V A S H Dalm
(VASH)
Anne A Schouffoer
(AA)
Jeska Kirsten de Vries-Bouwstra
(JK)
Dorota Krasowska
(D)
Piotr Leszczynsk
(P)
Bozena Kowalewska
(B)
Ivan Castellvi Barranco
(IC)
Juan Jose Alegre Sancho
(JJA)
Andrea Rubbert-Roth
(A)
Oliver Distler
(O)
Francesco Del Galdo
(F)
Christopher C Denton
(CC)
David D'Cruz
(D)
Ariane Herrick
(A)
Colin Baines
(C)
Bridget Griffiths
(B)
Karen Douglas
(K)
Informations de copyright
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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