Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Gene Expression Signatures in Polyarticular Juvenile Idiopathic Arthritis Predict Likelihood of Achieving Inactive Disease within Two Years of Treatment
Mason1, Rachel, Barnes2, Michael, Colbert3, Robert A., Thompson2, Susan D., Glass2, David N., Griffin2, Thomas A.
We tested the ability of recently identified gene expression signatures in polyarticular juvenile idiopathic arthritis (JIA) (Griffin, et al., Arthritis Rheum, 2009) to predict disease outcomes within two years of starting treatment with methotrexate and/or anti-tumor necrosis factor (TNF) medications. Signature I (S-I) contains monocyte-associated genes and correlates with more severe arthritis at baseline, while Signature III (S-III) is associated with reduced numbers of circulating T lymphocytes and is linked to milder arthritis at baseline.
S-I and S-III were quantified in peripheral blood mononuclear cells (PBMC) from a cohort of 59 subjects with recent-onset polyarticular JIA prior to treatment with methotrexate and/or anti-TNF medications. Clinical data from this observational study were reviewed at baseline through 24 months to identify subjects achieving inactive disease (ID) and those treated with anti-TNF medications. ID was defined as no joints with active arthritis, erythrocyte sedimentation rate levels within normal limits, and physician's global assessment of disease activity score of zero. Outcomes were compared between subject groups defined by S-I and S-III. Statistically significant differences were determined by chi-square analysis.
Fourteen subjects expressed only S-I, 12 subjects expressed only S-III, 12 subjects expressed both signatures, and 21 subjects expressed neither signature. ID was achieved at comparable rates for subjects with or without S-I (46% vs. 45 %). This contrasts with 58% of S-I subjects being treated with anti-TNF medications compared to only 30% of the other subjects (p=0.03). Conversely, ID was achieved by only 33% of S-III subjects compared to 54% of subjects lacking S-III (p=0.11), despite comparable rates of treatment with anti-TNF medications (46% vs. 40%). Notably, this difference in rate of achieving ID was quite pronounced when subjects expressing only S-III were compared to all other subjects (17% vs. 53% (p=0.02)).
Subjects expressing S-I, who clinically had more severe arthritis at baseline, were treated more often with anti-TNF medications, but achieved a similar rate of ID compared to other subjects. Conversely, subjects expressing S-III were treated with anti-TNF medications at comparable rates, but achieved a lower rate of ID. We speculate that S-III identifies a subset of polyarticular JIA patients with milder arthritis at baseline that is more difficult to control over time, warranting more aggressive early therapy than in current clinical practice. Thus, PBMC gene expression signatures may be useful tools for guiding therapy in polyarticular JIA.
To cite this abstract, please use the following information:
Mason, Rachel, Barnes, Michael, Colbert, Robert A., Thompson, Susan D., Glass, David N., Griffin, Thomas A.; Gene Expression Signatures in Polyarticular Juvenile Idiopathic Arthritis Predict Likelihood of Achieving Inactive Disease within Two Years of Treatment [abstract]. Arthritis Rheum 2009;60 Suppl 10 :248