ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1763

Baricitinib Reduces Proinflammatory Serum Cytokines in Patients with Systemic Lupus Erythematosus 

Thomas Dörner1, Yoshiya Tanaka2, Daniel Wallace3, Damiano Fantini4, Alisa Koch4, Maria Silk5, Jorge Ross Terres4, Jonathan Sims4, Peter Fischer6 and Michelle Petri7, 1Charite Universitätsmedizin Berlin and Deutsches Rheumaforschungszentrum (DRFZ), Berlin, Germany, 2University of Occupational and Environmental Health, Kitakyushu, Japan, 3Cedars-Sinai, Los Angeles, CA, 4Eli Lilly and Company, Indianapolis, IN, 5Eli Lilly and Company, Carmel, IN, 6Eli Lilly and Company, North Easton, MA, 7Johns Hopkins University School of Medicine, Baltimore, MD

Meeting: ACR Convergence 2021

Keywords:

Session Information

Date: Tuesday, November 9, 2021

Session Title: SLE – Treatment Poster (1732–1772)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: Baricitinib, a Janus kinase (JAK)1/JAK2 inhibitor, improved disease activity in systemic lupus erythematosus (SLE) adults receiving standard background therapy in a phase 2 trial (NCT02708095).1 The aim of this study was to elucidate the mechanism of action of baricitinib in SLE.  

Methods: Patients with SLE were treated with baricitinib-2mg or -4mg in a phase 2, randomized, placebo-controlled study. Sera from 68 patients (baricitinib-2mg: n=29; baricitinib-4mg: n=25; placebo: n=14) were collected at baseline and Week 12 and analyzed for cytokines using a Proximity Extension Assay (PEA) with 87 detectable analytes (Target 96 Inflammation Panel (Olink)). Interferon (IFN) scores were determined using a Modaplex assay. Spearman correlations were computed. Analyte changes from baseline at Week 12 were compared between baricitinib-4mg and placebo groups by Wilcoxon rank-sum or t-tests. Adjusted p< 0.05 was considered significant.

Results: At baseline, CXCL10 (r=0.50), CXCL11 (r=0.38), and CCL19 (r=0.45) correlated with the IFN signature. Confirming previous findings using Quanterix assays2, PEA analysis indicated that baricitinib-4mg, but not placebo, reduced IL-6 and IL-12p40 in SLE. Additionally, baricitinib-4mg significantly downregulated 1) serum cytokines that mediate lymphocyte and monocyte/macrophage recruitment (CCL19, TNFRSF9, TNF-β/Lymphotoxin-α), and 2) cytokines that induce bone turnover and augment joint pain (TRANCE/RANKL and Artemin).

Conclusion: These results suggest that downregulation of key cytokines that have proinflammatory and/or regulatory functions may play a role in the mechanism by which baricitinib acts to improve SLE disease activity.

References

1. Wallace DJ, et al. Lancet. 2018;392(10143):222-31.

2. Dörner T, et al. Lupus Sci Med. 2020;7(1).

Disclosures: T. Dörner, Eli Lilly, 2, Novartis, 2, Janssen, 2, GSK, 2, Sanofi, 2, Deutsche Forschungsgemeinschaft, 5, AbbVie, 2, Roche, 2, Boston Pharmaceuticals, 2; Y. Tanaka, Daiichi-Sankyo, 2, 5, 6, Eli Lilly, 6, Novartis, 6, YL Biologics, 6, Bristol-Myers Squibb, 6, Eisai, 5, 6, Chugai, 5, 6, AbbVie, 2, 5, 6, Astellas, 6, Pfizer, 6, Sanofi, 2, 6, Asahi-kasei, 5, 6, GSK, 2, 6, Mitsubishi-Tanabe, 5, 6, Gilead, 6, Janssen, 6, Takeda, 5, Ayumi, 2, Taisho, 2; D. Wallace, GlaxoSmithKline, 2, 6, Eli Lilly and Company, 2, 6, AstraZeneca, 2, 6, Aurunia, 2, 6, EMD Serono, 2; D. Fantini, Eli Lilly and Company, 3, 11; A. Koch, Eli Lilly and Company, 3; M. Silk, Eli Lilly and Company, 3, 11; J. Terres, Eli Lilly and Company, 3, 11; J. Sims, Eli Lilly and Company, 3; P. Fischer, Eli Lilly and Company, 3, 11; M. Petri, Alexion, 1, Amgen, 1, Astrazeneca, 1, 5, Aurinia, 5, 6, Eli Lilly, 5, Emergent Biosolutions, 1, Exagen, 5, Gilead Biosciences, 2, GSK, 1, 5, IQVIA, 1, Idorsia Pharmaceuticals, 2, Janssen, 1, 5, Merck EMD Serono, 1, Momenta Pharmaceuticals, 2, PPD Development, 1, Sanofi, 2, Thermofisher, 5, UCB Pharmaceuticals, 2.

To cite this abstract in AMA style:

Dörner T, Tanaka Y, Wallace D, Fantini D, Koch A, Silk M, Terres J, Sims J, Fischer P, Petri M. Baricitinib Reduces Proinflammatory Serum Cytokines in Patients with Systemic Lupus Erythematosus  [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/baricitinib%e2%80%afreduces-proinflammatory%e2%80%afserum-cytokines-in-patients-with-systemic-lupus-erythematosus%e2%80%af/. Accessed December 6, 2021.

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