Background Absolute monocyte counts after 3 months of treatment have been found to be predictive of clinical response to adalimumab at 6 months in rheumatoid arthritis (RA) patients1. It has also been shown that resistance to spontaneous apoptosis of monocytes in vitro predicts inadequate response to etanercept2. We hypothesise that absolute monocyte counts obtained from routine pre-treatment blood testing has predictive utility for treatment response to biologic agents.
Objectives To assess whether monocytes and other white blood cell subtypes are associated with treatment response at 6 months in RA patients.
Methods Full blood count (FBC) data was collected from patients attending 2 centres participating in the Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS), Manchester Royal Infirmary and Royal Lancaster Infirmary, from 2009–2015. BRAGGSS is a UK-based multi-centre inception cohort of secondary-care RA patients. Spearman correlation was carried out to explore relationships between pre-biologic differential white cell count (WCC) and absolute DAS28 (and its components) at treatment start (baseline) and 6 months. Logistic regression was used to explore associations between differential WCC and EULAR response at 6 months. Stata v13.1 was used for all statistical analyses.
Results 130 patients had WCC data available for analysis. They all satisfied American College of Rheumatology 1987 classification criteria for RA. 104 patients (80%) were female, with a mean age of 56.21 (SD 13.07). Mean baseline DAS28 score was 5.96 (SD 0.92) and mean monocyte count at baseline was 0.62*109/L (SD 0.22). Patients were on a variety of biologics: etanercept (n=56), adalimumab (n=24), rituximab (n=13), abatacept (n=10), golimumab (n=5), tocilizumab (n=12) and certolizumab (n=10).
Pre-treatment monocyte count was not associated with DAS28 at baseline, but correlated with DAS28 at 6 months (rho=0.19, p=0.028). When a cut-off of 0.62*109/L was used, high monocyte count was associated with DAS28>3.2 at 6 months (OR1.72 [95% CI 1.12–2.64], p=0.013), and with poor EULAR response (OR 2.82 [95% CI 1.12–7.13], p=0.028).
Neutrophil count was associated with DAS28 at both baseline (rho=0.22, p=0.013) and 6 months (rho=0.21, p=0.019). Neutrophil count was significantly associated with reduced odds of achieving a good EULAR response at 6 months (OR 0.82 [95% CI 0.69, 0.96], p=0.017). These neutrophil counts likely reflect ongoing inflammation, contributing to poor response to biologic therapy3.
Conclusions Monocyte counts were associated with increased DAS28 at 6 months, but not baseline, and with poor EULAR response at 6 months. This could provide a useful and widely available predictive biomarker, as FBC is routinely carried out in all patients commencing disease-modifying therapy in the UK. In future, monocyte count at baseline may be used to predict treatment response to biologics in RA patients at 6 months. Further studies with increased sample size are required to confirm these findings.
Chara L et al. Arthritis Res Ther 2012;14:R175.
Meusch U et al. Arthritis Res Ther 2013;15:R219.
Wright HL et al. Nat Rev Rheumatol 2014;10:593–601.
Disclosure of Interest None declared
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