Background Biomarkers who facilitate clinicians in decision making regarding the drugs that could be more effective for their patients with rheumatoid arthritis (RA) are needed.
Objectives To look for predictors of abatacept (ABA) therapy discontinuation in patients with RA.
Methods Seventy-one consecutive patients with RA who received treatment with intravenous ABA from 2008 to 2014 were enrolled. Demographical, clinical and laboratory parameters were evaluated, including peripheral blood T- and B-cell populations, rheumatoid factor and anti-cyclic citrullinated peptide (autoantibodies ACPA) isotypes, and serum free light chains. To evaluate the predictors of therapy discontinuation by logistic multivariable analysis, both variables associated with p<0.05 in univariable analysis, and variables previously reported by literature as potential confounders were considered. Receiver-operating characteristic (ROC) analysis was used to verify the applicability of predictive biomarkers. The Kaplan-Meier method and the log-rank test were applied to compare the probability of discontinuing therapy in the different groups.
Results Comparing patients who discontinued ABA (n:28) with those still in therapy (n:41) we observed: a higher proportion of smokers (51.9% vs 25.6%; p=0.03); a lower proportion of terminally-differentiated effector-memory cells (TDEM) among total CD8+ T-lymphocytes at baseline (22.0% (7.8–39.2) vs 38.7% (20.7–55.9); p=0.002). The proportion of patients with positivity for ACPA was lower among patients who discontinued ABA, but not significantly (76% vs 89.5%; p=0.13). Logistic multivariate analysis showed that only the proportion of CD8+TDEM T-cells was an independent predictive factor of therapy discontinuation (OR (95% IC)=6.2 (1.2 to 30.8); p=0.026). ROC analysis showed a significant performance of this biomarker for prediction of therapy discontinuation (using a cut-off of 30.6%: AUC: 0.760+0.07; p=0.002). Patients with a low proportion of CD8+TDEM at baseline had a higher probability of discontinuing the treatment during time (log-rank test: p<0.01).
Conclusions A high number of circulating TDEM T-cells might be a marker of a stronger activation of costimulatory signals in the history of RA patients. It might be speculated that these patients may be particularly responsive to costimulation blockade by ABA. T-cell characterization for identification of TDEM CD8+ T-cells might be a useful test to predict discontinuation of ABA therapy.
Smolen JS, et al. Ann Rheum Dis 2014; 73:492–509.
Isaacs JD, et al. Ann Rheum Dis 2013; 72:329–336.
Scarsi M, et al. J Rheumatol 2011; 38:2105–2111.
Gottenberg JE, et al. Ann Rheum Dis 2012; 71:1815–1819.
Acknowledgement Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduct and did not interfere with the conception and design of the study, acquisition, analysis, interpretation of data, and manuscript drafting. The authors declare that they have no other competing interests.
Disclosure of Interest None declared