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Genes Hold Key To Nonresponse To Biologics in JIA


 

VIENNA — The day is fast approaching when physicians will be able to forecast which juvenile idiopathic arthritis patients will respond to anti-tumor necrosis factor-α therapy based upon gene-expression profiling conducted after just a few days of treatment, Dr. Joern Kekow predicted at the annual European congress of rheumatology.

About 30% of JIA patients prove to be nonresponders to anti-TNF-7alpha; therapy. The ability to selectively target it to those most likely to benefit while sparing others from needless exposure to side effects and expense will be a most welcome development, observed Dr. Kekow of the University of Magdeburg (Germany).

She reported on nine patients, mean age 15, with JIA—five with oligoarthritis, three with enthesis-related arthritis, and one with psoriatic arthritis—who underwent microarray analysis of the expression of 22,000 of their genes prior to and again 72 hours after starting etanercept or infliximab therapy.

Expression of roughly 500 genes proved to be significantly upregulated or downregulated in at least five of the nine patients within the first 3 days of anti-TNF-α therapy. Changes in the expression of a subgroup of these genes correlated strongly with clinical outcomes as assessed at 3 months.

The promising candidates include uPAR, GADD34, ICAM-1, TNF-α, interferon-1β, MIP-1α, manganese superoxide dismutase, COX-2, PBEF, and GRO-α, she said at the meeting, sponsored by the European League Against Rheumatism.

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