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Association of baseline cytokine levels with anti-tumour necrosis factor treatment response in
rheumatoid arthritis
David S. Gibson1, Cathy M. McGeough1, Mary Slevin1, Gary Wright2, Philip Gardiner3, Helena A.
Murray4, Mark J. Latten4, Martin A. Crockard4, John V. Lamont4, Tony J. Bjourson1.
1. Ulster University, Northern Ireland Centre for Stratified Medicine, Londonderry, UK.
2. Department of Rheumatology, Musgrave Park Hospital, Belfast, UK.
3. Department of Rheumatology, Altnagelvin Hospital, Londonderry, UK.
4. Randox Laboratories Ltd., Crumlin, UK.
Background
Clinical trials of anti-tumour necrosis factor alpha (TNF) have shown efficacy in 60-70% of
rheumatoid arthritis patients (RA). Predicting response to anti-TNF drugs at baseline remains an
elusive goal in RA management. The purpose of this study was to determine if baseline levels of
circulating cytokines, soluble receptors, adhesion molecules and metabolic factors differentiate
future responders.
Methods
29 RA patients with active disease were recruited, who had failed on disease modifying drugs and
were recommended for anti-TNF treatment. Peripheral blood samples were collected at baseline.
Responders were identified by a ≥1.2 reduction in disease activity score (DAS28-ESR) at 6 months.
Five protein arrays quantified 33 proteins in pre-treatment plasma (Cytokine I, III and IV; Metabolic I;
Adhesion molecule; Randox Laboratories Ltd., UK). Data was analysed by Pearson ranked correlation
and logistic regression to clinical measures of disease activity at baseline and six months anti-TNF
treatment.
Results
Elevated levels of interleukin 8 (p=0.043), monocyte chemoattractant protein (p=0.027),
granulocyte-macrophage colony-stimulating factor (p=0.020) and soluble interleukin 2α receptor
(p=0.01) were associated with high TJC at baseline. No significant relationship with the protein array
panels was recorded relative to baseline DAS28-ESR. Significant inverse correlations were observed
between absolute change in DAS28-ESR after 6 months of anti-TNF therapy and baseline levels of
interleukin 6 (p=0.026) and resistin (p=0.044).
Conclusions
These findings suggest that baseline levels of specific circulating proteins may help to differentiate
RA patient responders to all currently available anti-TNF therapies.