TY - JOUR
T1 - Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis
AU - Spiera, Robert
AU - Kuwana, Masataka
AU - Khanna, Dinesh
AU - Hummers, Laura
AU - Frech, Tracy M.
AU - Stevens, Wendy
AU - Matucci-Cerinic, Marco
AU - Kafaja, Suzanne
AU - Distler, Oliver
AU - Jun, Jae Bum
AU - Levy, Yair
AU - Leszcyzński, Piotr
AU - Gordon, Jessica
AU - Steen, Virginia
AU - Lee, Eun Bong
AU - Jankowski, Tomasz
AU - Litinsky, Irena
AU - Chung, Lorina
AU - Hsu, Vivien
AU - Mayes, Maureen
AU - Sandorfi, Nora
AU - Simms, Robert W.
AU - Finzel, Stephanie
AU - de Vries-Bouwstra, Jeska
AU - Constantine, Scott
AU - Dgetluck, Nancy
AU - Dinh, Quinn
AU - Bloom, Bradley J.
AU - Furst, Daniel E.
AU - White, Barbara
AU - Denton, Christopher P.
N1 - Publisher Copyright:
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2023/9
Y1 - 2023/9
N2 - Objective: 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). Methods: 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). Results: 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. Conclusion: 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.
AB - Objective: 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). Methods: 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). Results: 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=85162068468&partnerID=8YFLogxK
U2 - 10.1002/art.42510
DO - 10.1002/art.42510
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C2 - 37098795
AN - SCOPUS:85162068468
SN - 2326-5191
VL - 75
SP - 1608
EP - 1618
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 9
ER -