Julio C Mantero1, Nina Kishore1, Jessica Ziemek1, Giuseppina Stifano1, Christopher Zammitti1, Dinesh Khanna2, Jessica K Gordon3, Robert Spiera3, Yuqing Zhang4, Robert W Simms1, Robert Lafyatis5. 1. Department of Rheumatology, Boston University Medical Center, Boston, MA, USA. 2. Department of Rheumatology, University of Michigan Medical Center, Ann Arbor, MI, USA. 3. Department of Rheumatology, Hospital of Special Surgery, New York, NY, USA. 4. Division of Epidemiology, Massachusetts General Hospital, Boston, MA, USA. 5. Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. rlafyatis@gmail.com.
Abstract
OBJECTIVES: This clinical trial was designed to study the safety and efficacy of blocking IL-1 in skin fibrosis of patients with diffuse cutaneous systemic sclerosis (dcSSc), and to test the hypothesis that inhibition of IL-1 by rilonacept will downregulate expression of the 2G SSc gene biomarker as a surrogate for the modified Rodnan skin score (MRSS). METHODS:19 dcSSc patients were randomised 2:1 active treatment:placebo in this double blinded trial. Study patients received weekly treatments with either subcutaneous rilanocept 320 mg loading dose at day 0 and then 160 mg for each of the 5 subsequent weekly doses, or placebo. Skin biopsies were taken to test 2G SSc biomarker gene expression at day 0 before treatment and one week after the final study drug dose, comparing gene expression changes between rilonacept- and placebo-treated patients, as well as the change in gene expression at week 6 compared to baseline in rilonacept-treated patients. Safety assessments extended to 6 weeks after the final dose of study drug or placebo. Other secondary outcome measures included global and IL-1-regulated gene expression, serum biomarkers and the MRSS. RESULTS: Rilonacept compared to placebo-treated patients did not show any treatment-related effect on the 2G SSc biomarker. Rilonacept treatment also failed to alter IL-6 expression in skin, serum IL-6, C-reactive protein, or CCL18, a marker of IL-6 activity in SSc. CONCLUSIONS: In this small trial we did not observe any effect of blocking IL-1 on clinical skin disease or biomarkers of IL-1 activity.
RCT Entities:
OBJECTIVES: This clinical trial was designed to study the safety and efficacy of blocking IL-1 in skin fibrosis of patients with diffuse cutaneous systemic sclerosis (dcSSc), and to test the hypothesis that inhibition of IL-1 by rilonacept will downregulate expression of the 2G SSc gene biomarker as a surrogate for the modified Rodnan skin score (MRSS). METHODS: 19 dcSSc patients were randomised 2:1 active treatment:placebo in this double blinded trial. Study patients received weekly treatments with either subcutaneous rilanocept 320 mg loading dose at day 0 and then 160 mg for each of the 5 subsequent weekly doses, or placebo. Skin biopsies were taken to test 2G SSc biomarker gene expression at day 0 before treatment and one week after the final study drug dose, comparing gene expression changes between rilonacept- and placebo-treated patients, as well as the change in gene expression at week 6 compared to baseline in rilonacept-treated patients. Safety assessments extended to 6 weeks after the final dose of study drug or placebo. Other secondary outcome measures included global and IL-1-regulated gene expression, serum biomarkers and the MRSS. RESULTS: Rilonacept compared to placebo-treated patients did not show any treatment-related effect on the 2G SSc biomarker. Rilonacept treatment also failed to alter IL-6 expression in skin, serum IL-6, C-reactive protein, or CCL18, a marker of IL-6 activity in SSc. CONCLUSIONS: In this small trial we did not observe any effect of blocking IL-1 on clinical skin disease or biomarkers of IL-1 activity.
Authors: Daniel Wolff; Vedran Radojcic; Robert Lafyatis; Resat Cinar; Rachel K Rosenstein; Edward W Cowen; Guang-Shing Cheng; Ajay Sheshadri; Anne Bergeron; Kirsten M Williams; Jamie L Todd; Takanori Teshima; Geoffrey D E Cuvelier; Ernst Holler; Shannon R McCurdy; Robert R Jenq; Alan M Hanash; David Jacobsohn; Bianca D Santomasso; Sandeep Jain; Yoko Ogawa; Philipp Steven; Zhonghui Katie Luo; Tina Dietrich-Ntoukas; Daniel Saban; Ervina Bilic; Olaf Penack; Linda M Griffith; Meredith Cowden; Paul J Martin; Hildegard T Greinix; Stefanie Sarantopoulos; Gerard Socie; Bruce R Blazar; Joseph Pidala; Carrie L Kitko; Daniel R Couriel; Corey Cutler; Kirk R Schultz; Steven Z Pavletic; Stephanie J Lee; Sophie Paczesny Journal: Transplant Cell Ther Date: 2021-06-10