Infliximab Treatment of Rheumatoid Arthritis Patients Simultaneously Increases TNF‐α Protein Levels and Reduces mRNA Expression in the Blood

Hjelmevik, T. O.; Kvalvik, A. G.; Knappskog, P. M.; Lefsaker, L.; Kleiven, A. S.; Dyvik, S.; Brun, J. G.; Østergaard, H.; Eiken, H. G.

Objective: Tumour necrosis factor‐α (TNF‐α) is an important mediator in the pathogenesis of rheumatoid arthritis (RA). We have investigated long‐term anti‐TNF‐α treatment with infliximab with respect to TNF‐α gene activity and protein levels in the blood of RA patients and disease activity score (DAS). Methods: TNF‐α mRNA and plasma protein in RA patients (n = 29) and healthy controls (n = 24) was determined before and during treatment with infliximab (3 mg/kg) using real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) and high sensitivity enzyme‐linked immunosorbent assay (ELISA), respectively. The disease activity of the patients was assessed as DAS value. Results: The TNF‐α mRNA levels of RA patients at baseline were higher than that of the control group (P = 0.0135) but were significantly reduced after initiation of treatment (P < 0.001). Low mRNA levels were sustained throughout the 54 weeks of the study. Baseline protein levels of RA patients were similar to the control group. After 2 weeks of treatment, the protein levels were significantly elevated from baseline (P = 0.0353) and increased throughout week 14. Clinical improvement for all RA patients was found upon infliximab treatment, as a reduction in DAS values (P < 0.001). The increase in protein and reduction in DAS value from week 2–14 was also correlated (P = 0.0374). Conclusion: During infliximab treatment of RA patients, there is an accumulation in immune‐reactive TNF‐α protein in blood plasma and simultaneously a reduction in TNF‐α gene expression in PBMC, which may in part explain the beneficial course of RA symptoms.