Treatment
Randomised, double-blind, placebo-controlled trial of IL1-trap, rilonacept, in systemic sclerosis. A phase I/II biomarker trial
J.C. Mantero1, N. Kishore2, J. Ziemek3, G. Stifano4, C. Zammitti5, D. Khanna6, J.K. Gordon7, R. Spiera8, Y. Zhang9, R.W. Simms10, R. Lafyatis11
- Department of Rheumatology, Boston University Medical Center, Boston, MA, USA.
- Department of Rheumatology, Boston University Medical Center, Boston, MA, USA.
- Department of Rheumatology, Boston University Medical Center, Boston, MA, USA.
- Department of Rheumatology, Boston University Medical Center, Boston, MA, USA.
- Department of Rheumatology, Boston University Medical Center, Boston, MA, USA.
- Department of Rheumatology, University of Michigan Medical Center, Ann Arbor, MI, USA.
- Department of Rheumatology, Hospital of Special Surgery, New York, NY, USA.
- Department of Rheumatology, Hospital of Special Surgery, New York, NY, USA.
- Division of Epidemiology, Massachusetts General Hospital, Boston, MA, USA.
- Department of Rheumatology, Boston University Medical Center, Boston, MA, USA.
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. rlafyatis@gmail.com
CER11243
2018 Vol.36, N°4 ,Suppl.113
PI 0146, PF 0149
Treatment
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PMID: 30277862 [PubMed]
Received: 13/03/2018
Accepted : 23/07/2018
In Press: 30/09/2018
Published: 30/09/2018
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.
