Session Information
Date: Monday, November 9, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment III: Biomarkers
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
The Phase IIb IM101-042 trial was a
randomized, double-blind, placebo-controlled trial of abatacept (ABA) in
systemic lupus erythematosus patients (pts) with polyarthritis, discoid lesions
or serositis. Pts were randomized 2:1 to receive ABA (monthly ~10 mg/kg; n=98)
or placebo (pbo; n=46) following a month of high-dose corticosteroids, and with
continuing background immunosuppression. To gain insights into responses to ABA
in pathologic subsets of SLE, the current study applied a de-convolution
algorithm to pts’ baseline transcriptomic data from whole blood mRNA.
types1 were used in conjunction with a de-convolution algorithm2
to identify cell proportions from whole blood transcriptomic data obtained by
gene chip analysis of PAXgene mRNA in the 144 pt samples collected at trial
baseline (before ABA or pbo) and 10 healthy volunteers. The de-convoluted pt-level
data were used in an unsupervised analysis to generate consensus clustering for
stratification. Pt clusters were then used to perform a post hoc
analysis of clinical study results.
levels of activated natural killer (NK) cells and neutrophils were seen in SLE pts
vs healthy volunteers at baseline, while NK and T helper (Th) cells were lower
in SLE pts than in healthy volunteers. At baseline, SLE pts were stratified by
immune cell fractions into 4 major clusters characterized by a dominance of the
listed cell type: C1, high Th cells; C2, high plasma cells (PCs); C3, high
neutrophils, activated monocytes and activated dendritic cells; and C4, high B
or NK cells. Median and average total British Isles Lupus Assessment Group (BILAG)
scores at baseline were similar across all clusters and treatment arms. The C2
cluster (high PCs) contained most of the pts with high levels of anti-dsDNA. C1
cluster pts were the slowest to flare, regardless of treatment allocation (>170
days). In the C3 cluster, ABA-treated pts were slower to flare than pbo pts (mean
194 vs 96 days) and had the largest decrease in total BILAG score and greatest
difference from pbo (Figure).
blood de-convolution identified 4 distinct peripheral blood mononuclear cell
phenotypic clusters at baseline. These clusters demarcated distinct clinical
characteristics and response to therapy. Whole blood de-convolution might
provide insights into specific immune cell-driven disease pathogenesis and
might improve patient stratification and enrich interpretation of trial data.
2009;4:e6098.
Rheum 2010;62:3077–87.
Disclosure: S. Bandyopadhyay, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; S. Connolly, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; O. Jabado, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; S. Kelly, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; M. Maldonado, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; R. Westhovens, Roche Pharmaceuticals, 2,Bristol-Myers Squibb, 8,Janssen, Galapagos, 5; P. Nash, Abbvie, Amgen, BMS< Janssen, Pfizer, Roche, Sanofi, Lily, MSD, Novartis, Celgene, UCB Newbridget, 2,Abbvie, Amgen, BMS< Janssen, Pfizer, Roche, Sanofi, Lily, MSD, Novartis, Celgene, UCB Newbridget, 5,Abbvie, Amgen, BMS< Janssen, Pfizer, Roche, Sanofi, Lily, MSD, Novartis, Celgene, UCB Newbridget, 8; J. Merrill, Bristol-Myers Squibb, GlaxoSmithKline, Xencor Macrogenics, 2,Bristol-Myers Squibb, GlaxoSmithKline, Mallinckrodt, MedImmune, Lilly, UCB, Takeda, Abbvie, Anthera, Neovacs, Receptos, Celgene, 5; R. Townsend, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3.
To cite this abstract in AMA style:
Bandyopadhyay S, Connolly S, Jabado O, Kelly S, Maldonado M, Westhovens R, Nash P, Merrill J, Townsend R. De-Convolution of Whole Blood Transcriptomic Data from a Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial of Abatacept in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/de-convolution-of-whole-blood-transcriptomic-data-from-a-phase-iib-randomized-double-blind-placebo-controlled-trial-of-abatacept-in-systemic-lupus-erythematosus/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/de-convolution-of-whole-blood-transcriptomic-data-from-a-phase-iib-randomized-double-blind-placebo-controlled-trial-of-abatacept-in-systemic-lupus-erythematosus/