Treatment Of Psoriasis Patients With IMO-3100 Shows Improvement In Gene Expression Patterns Of Meta-Analysis Derived-3 Transcriptome and IL-17 Pathway

Mayte Suarez-Farinas¹, Jennifer Belasco¹, Tim Sullivan², Robert Arbeit² and James G. Krueger¹, ¹Krueger Laboratory, The Rockefeller University, New York, NY, ²Idera Pharmaceuticals, Inc., Cambridge, MA

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: autoimmune diseases and toll-like receptors, Gene Expression

Session Information

Title: Innate Immunity and Rheumatic Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose:

IMO‑3100, an antagonist of TLRs 7 and 9, has shown significant improvement in Psoriasis Area and Severity Index (PASI) scores in a randomized, double‑blind, placebo‑controlled Phase 2 trial in patients with moderate‑to‑severe plaque psoriasis. In the Phase 2 clinical trial, 44 patients were randomized to receive 4 once‑weekly injections (Days 1, 8, 15, and 22) of IMO‑3100 at 0.16 or 0.32 mg/kg or placebo; 40 patients were clinically evaluable, and clinical data were presented at IID 2013. To evaluate immunological changes following treatment with IMO-3100, biopsy samples were obtained on Days 1 (lesional and normal skin) and 29 (lesional skin). Biopsy samples from six patients in the 0.16-mg/kg group with positive clinical responses and six placebo patients also were used for gene expression analysis by DNA microarray.

Methods:

Meta-analysis derived (MAD)-3 transcriptome represents a gene-expression profile associated with psoriasis (PLoS ONE 7(9): e44274). The overall effect of IMO-3100 vs. placebo treatment on the psoriasis transcriptome was compared by gene set enrichment analysis (GSEA).

Results:

Principal component analysis of the microarray data showed clear distinction between lesional and normal skin within the twelve patients. Analysis showed that IMO-3100-treated patients had significant improvement in MAD-3 gene profile compared to placebo-treated patients. Placebo treatment did not significantly modulate gene expression, whereas genes up-regulated in the psoriasis transcriptome were significantly (p<10^-16) improved by IMO-3100 treatment. GSEA identified strong improvements in genes regulated in keratinocytes by IL-17 and the combination of IL-17 and TNF. In addition to the DNA microarray analysis, gene expression targets were analyzed by qPCR, which showed IL-17 was downregulated in IMO-3100 treated patients with PASI improvements.

Conclusion:

In summary, treatment of patients with psoriasis with IMO-3100 leads to down regulation of the IL-17 pathway, which is central to the pathogenesis of psoriasis.

Disclosure:

M. Suarez-Farinas,

Idera Pharmaceuticals,

J. Belasco,

Idera Pharmaceuticals, Inc.,

T. Sullivan,

Idera Pharmaceuticals, Inc.,

R. Arbeit,

Idera Pharmaceuticals, Inc.,

J. G. Krueger,

Idera Pharmaceuticals, Inc.,

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