Background Clinical response remains difficult to predict in patients with rheumatoid arthritis (RA). Acute phase reactants (APRs) C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are regularly measured in standard care, and abnormal CRP and ESR are frequently used as inclusion criteria for RA clinical trials. Alone or in combination with demographic, clinical, and imaging parameters, these APRs are often considered important in treatment decisions in RA. However, results of these tests for inflammation are discordant in a substantial proportion of patients,^1–3 and the clinical implications of discordant CRP:ESR findings have not been well studied.

Objectives To explore the relationship between clinical response and baseline CRP:ESR discordance in RA.

Methods Randomized patients with moderate-severe RA who participated in 3 etanercept (ETN) clinical trials^4–6 and had both APR measurements were included in these post hoc analyses. To allow comparison, baseline CRP and ESR were standardized to the same scale by subtracting the respective means and dividing by the respective standard deviations for each patient. Standardized CRP was subtracted from standardized ESR and differences categorized by quartile (cutoffs: Q1, –0.5; median, 0; Q3, 0.5). DAS28 (ESR) low disease activity (LDA) and remission after 16 or 52 weeks of treatment with ETN + methotrexate (MTX) were analyzed by quartile of CRP:ESR discordance.

Results Across clinical trials, 693 patients received ETN+MTX and had CRP and ESR measured. After 16 or 52 weeks of ETN+MTX treatment, significantly higher proportions of patients achieved DAS28 LDA and remission in the group with higher CRP than ESR at baseline (lower ESR/higher CRP); lower proportions of responders were seen in the group with similar CRP and ESR (ESR$≈ $CRP), and the lowest proportion in the group with lower CRP than ESR (higher ESR/lower CRP) (Table).

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Conclusions In clinical trials, elevated CRP relative to ESR at baseline was a significantly better predictor of the ability of active treatment to show clinical response after 4 months or 1 year of combination etanercept-methotrexate therapy than similar CRP and ESR or lower CRP vs higher ESR. These findings underscore the importance of incorporating this readily available biomarker (CRP) into clinical trial settings; whether this is true in clinical practice cannot be determined from this data set but should be investigated prospectively.

1. Costenbader KH, et al. Clin Exp Rheumatol. 2007;25:746–9.

2. Feldman M, et al. Transl Res. 2013;161:37–43.

3. Kay J, et al. Arthritis Res Ther. 2014:16:R40.

4. Klareskog L, et al. Lancet. 2004;363:675–81.

5. Emery P, et al. Lancet. 2008;372:375–82.

6. Kim HY, et al. Int J Rheum Dis. 2012;15:188–96.

Disclosure of Interest R. Fleischmann Consultant for: Pfizer, A. Szumski Employee of: inVentiv Health, H. Jones Shareholder of: Pfizer, Employee of: Pfizer