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Increased Tumor Necrosis Factor-α mRNA Expression in Whole Blood from Patients with Rheumatoid Arthritis: Reduction After Infliximab Treatment Does Not Predict Response

ALEXANDRE PACHOT, BÉATRICE ARNAUD, HUBERT MARROTE, MARIE-ANGÉLIQUE CAZALIS, JENNIFER DIASPARRA, AURORE GOURAUD, BRUNO MOUGIN, and PIERRE MIOSSEC

ABSTRACT.

Objective.
It has been suggested that patients with rheumatoid arthritis (RA) with abundant tumor necrosis factor-a (TNF-a) are more likely to respond to TNF-a inhibitors. We measured expression of TNF-a mRNA in peripheral blood of RA patients undergoing infliximab treatment in order to test its predictive value for treatment response.

Methods. Forty-four RA patients showing persistent disease activity and 27 healthy controls were studied. Peripheral blood TNF-a mRNA levels were measured before and 4 hours after the first infliximab infusion and at Week 22 using quantitative RT-PCR. Results were correlated to the treatment response at Week 22 in the whole RA cohort and a subset of patients showing high TNF-a mRNA levels at baseline.

Results. At baseline and at Week 22, TNF-a mRNA expression in RA patients was significantly increased compared to healthy controls. At both timepoints, no significant difference was observed between responders and nonresponders. Compared to baseline, infliximab treatment induced a decrease in TNF-a mRNA level at 4 hours and at Week 22, although this effect was significant only in patients with high TNF-a mRNA expression at baseline. Such variation compared to baseline was similar in responders and nonresponders.

Conclusion. Peripheral blood TNF-a mRNA expression is increased in RA, but its reduction with anti-TNF treatment is not associated with treatment response. (First Release Sept 15 2007; J Rheumatol 2007;34:2158-61)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
TUMOR NECROSIS FACTOR-a
mRNA
INFLIXIMAB


From the Joint Unit, Hospices Civils de Lyon – bioMérieux, Hôpital Edouard Herriot; and the Clinical Immunology Unit, Department of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.

A. Pachot, PharmD, PhD; B. Arnaud; M-A. Cazalis; J. Diasparra; A. Gouraud, PharmD; B. Mougin, PharmD, PhD, Joint Unit, Hospices Civils de Lyon – bioMérieux; H. Marrote, MD, PhD; P. Miossec, MD, PhD, Joint Unit, Hospices Civils de Lyon – bioMérieux and Clinical Immunology Unit, Department of Immunology and Rheumatology, Hôpital Edouard Herriot.

Address reprint requests to Dr. P. Miossec, Clinical Immunology Unit, Department of Immunology and Rheumatology, Hôpital Edouard Herriot, 5 place d'Arsonval, 69003 Lyon, France. E-mail: pierre.miosse@chu-lyon.fr

Accepted for publication July 5, 2007.




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