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Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis.
Spiera, Robert; Kuwana, Masataka; Khanna, Dinesh; Hummers, Laura; Frech, Tracy M; Stevens, Wendy; Matucci-Cerinic, Marco; Kafaja, Suzanne; Distler, Oliver; Jun, Jae-Bum; Levy, Yair; Leszcyznski, Piotr; Gordon, Jessica; Steen, Virginia; Lee, Eun Bong; Jankowski, Tomasz; Litinsky, Irena; Chung, Lorina; Hsu, Vivien; Mayes, Maureen; Sandorfi, Nora; Simms, Robert W; Finzel, Stephanie; de Vries-Bouwstra, Jeska; Constantine, Scott; Dgetluck, Nancy; Dinh, Quinn; Bloom, Bradley J; Furst, Daniel E; White, Barbara; Denton, Christopher P.
Afiliação
  • Spiera R; Weill Cornell Medical College, New York, New York.
  • Kuwana M; Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
  • Khanna D; University of Michigan, Ann Arbor.
  • Hummers L; John Hopkins University School of Medicine, Baltimore, Maryland.
  • Frech TM; University of Utah and Salt Lake City VA Health Care System, Salt Lake City, Utah.
  • Stevens W; St. Vincent's Hospital, Melbourne, Victoria, Australia.
  • Matucci-Cerinic M; Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy.
  • Kafaja S; David Geffen School of Medicine at University of California, Los Angeles (UCLA).
  • Distler O; University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Jun JB; Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
  • Levy Y; Meir Medical Center, Kfar Saba, Israel.
  • Leszcyznski P; Medyczne Centrum Hetmanska, Poznan, Poland.
  • Gordon J; Weill Cornell Medical College, New York, New York.
  • Steen V; Georgetown University School of Medicine, Washington, DC.
  • Lee EB; Seoul National University College of Medicine, Seoul, South Korea.
  • Jankowski T; Klinika Reumatologii Ukladowych Chorob Tkanki Lacznej Szpital Uniwersytecki, Bydgozzcz, Poland.
  • Litinsky I; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • Chung L; Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, California.
  • Hsu V; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.
  • Mayes M; McGovern Medical School, The University of Texas Health Science Center at Houston.
  • Sandorfi N; Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
  • Simms RW; Boston University School of Medicine, Boston, Massachusetts.
  • Finzel S; Department of Rheumatology and Clinical Immunology, University Medical Center, Universitätsklinikum Freiburg, Freiburg, Germany.
  • de Vries-Bouwstra J; Leiden University Medical Center, Leiden, The Netherlands.
  • Constantine S; Corbus Pharmaceuticals, Inc., Norwood, Massachusetts.
  • Dgetluck N; Corbus Pharmaceuticals, Inc., Norwood, Massachusetts.
  • Dinh Q; Corbus Pharmaceuticals, Inc., Norwood, Massachusetts.
  • Bloom BJ; Corbus Pharmaceuticals, Inc., Norwood, Massachusetts.
  • Furst DE; Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy, David Geffen School of Medicine at UCLA, Los Angeles, California, and University of Washington, Seattle, UK.
  • White B; Corbus Pharmaceuticals, Inc., Norwood, Massachusetts.
  • Denton CP; UCL Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital Campus, University College London Medical School, London, UK.
Arthritis Rheumatol ; 75(9): 1608-1618, 2023 09.
Article em En | MEDLINE | ID: mdl-37098795
ABSTRACT

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 111 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Escleroderma Sistêmico / Esclerodermia Difusa Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Revista: Arthritis Rheumatol Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Escleroderma Sistêmico / Esclerodermia Difusa Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Revista: Arthritis Rheumatol Ano de publicação: 2023 Tipo de documento: Article