ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1894

Baricitinib-Associated Changes in Type l Interferon Gene Signature during a 24-Week Phase-2 Clinical SLE Trial

Thomas Dörner1, Yoshiya Tanaka2, Michelle Petri3, Josef S. Smolen4, Ernst R. Dow5, Richard E. Higgs5, Robert J. Benschop5, Adam Abel5, Maria E. Silk5, Stephanie de Bono5 and Robert W. Hoffman5, 1Charité Universitätsmedizin Berlin and Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin, Germany, 2University of Occupational and Environmental Health, Kitakyushu, Japan, 3Johns Hopkins University School of Medicine, Baltimore, MD, 4Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria, 5Eli Lilly and Company, Indianapolis, IN

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Date: Monday, October 22, 2018

Title: 4M108 ACR Abstract: SLE–Etiology & Pathogenesis I (1893–1898)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: In the phase 2 study JAHH (NCT02708095), treatment with baricitinib (bari), an oral selective Janus kinase 1/2 inhibitor approved for the treatment of RA, resulted in significant improvements in patients with active SLE receiving standard background therapy compared with placebo (PBO).1 Expression of type l-associated IFN responsive genes (IRGs) is elevated in patients (pts) with SLE.2 We developed a robust quantitative assay to measure changes in the IFN signature. We then examined the relationship between the IFN signature and measures of clinical outcome.

Methods: A total of 314 pts were randomized in a 1:1:1 ratio to receive PBO, bari 2- or 4-mg once daily for 24 weeks (Wks) in study JAHH. Total RNA isolated from whole blood collected in PAX gene tubes was analyzed using a multiplex quantitative (qPCR) assay panel of 6 IRGs on the Modaplex at baseline (BL), and Wks 2, 12, and 24. The assay was developed and optimized using RNA samples from 1760 patients with SLE enrolled in phase 3 trials of tabalumab (an anti-B cell activating factor monoclonal antibody),2 along with controls from healthy blood donors. The IFN signature assay produced a bimodal distribution.

Results: 70% of pts had an elevated IFN signature at BL. Bari significantly reduced the IFN signature by Wk 24 compared with PBO (2-mg: -20%, 4-mg: -24%, p≤0.05), with decreases observed as early as Wk 2. In the pts who had a high IFN signature at BL, bari 4-mg significantly reduced the IFN signature at Wk 12 (-24%) and Wk 24 (-23%) compared with PBO (p≤0.01); decreases were also observed at Wks 12 and 24 with the 2-mg dose, but the difference from PBO was not statistically significant, consistent with a dose-response effect. Bari 4-mg treatment resulted in significant clinical improvement in the resolution of arthritis or rash determined by the SLEDAI-2K.1 However, the effect of bari on IFN signature reduction (change from BL as well as absolute BL value) did not correlate with SLEDAI-2K-defined clinical improvement at Wk 12 or 24.

Conclusion: A dose-dependent decrease in the IFN signature was observed in bari-treated pts with SLE. Treatment with bari resulted in clinical improvement across various measures of SLE disease activity.1 Moreover, response was observed with bari regardless of the change in the IFN gene signature. These data suggest that the clinical improvement observed in bari-treated pts with SLE may be the result of bari-mediated effects on multiple cytokine pathways that may include, but are not limited to, IFN signaling.

1Wallace D et al. DOI: 10.1136/annrheumdis-2018-eular.1918

2Hoffman R et al. Arthritis Rheumatol. 2017;69:643-654.

Disclosure: T. Dörner, Chugai, Janssen, Roche, Sanofi, 2,AbbVie, Celgene, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche, UCB, 5,Amgen, Biogen, Celgene, 8; Y. Tanaka, Abbvie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Takeda, Taisho-Toyama, 2,Abbvie, Asahi-kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, GSK, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, Takeda, UCB, YL biologics, 8; M. Petri, Eli Lilly and Comany, 5; J. S. Smolen, AbbVie, Eli Lilly and Company, Janssen, MSD, Pfizer, Roche, 2,AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead, Glaxo, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB, 5; E. R. Dow, Eli Lilly and Company, 1, 3; R. E. Higgs, Eli Lilly and Company, 1, 3; R. J. Benschop, Eli Lilly and Company, 1, 3; A. Abel, Eli Lilly and Company, 1, 3; M. E. Silk, Eli Lilly and Company, 1, 3; S. de Bono, Eli Lilly and Company, 1, 3; R. W. Hoffman, Eli Lilly and Company, 1, 3.

To cite this abstract in AMA style:

Dörner T, Tanaka Y, Petri M, Smolen JS, Dow ER, Higgs RE, Benschop RJ, Abel A, Silk ME, de Bono S, Hoffman RW. Baricitinib-Associated Changes in Type l Interferon Gene Signature during a 24-Week Phase-2 Clinical SLE Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/baricitinib-associated-changes-in-type-l-interferon-gene-signature-during-a-24-week-phase-2-clinical-sle-trial/. Accessed .

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