Date: Monday, November 9, 2015
Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
The prediction of a stable treatment for rheumatoid arthritis (RA) is one of the targets of clinical research in rheumatology. However, only few biomarkers were successfully described as predictors of retention in therapy with biological agents. The aim of this paper was to investigate whether T-cell characterization might be used as predictor of abatacept (ABA) treatment continuation.
Data are expressed as median (10th-90thpercentile), if not otherwise specified. Seventy-one consecutive RA patients treated with ABA were prospectively followed (female: 80%; age: 54 (40-71) years; disease duration: 7 (1-19) years; rheumatoid factor positivity: 81%; anti-cyclic citrullinated peptide (ACPA) positivity: 83%; DAS-28 (CRP): 5.1 (3.9-6.5); number of previous disease-modifying antirheumatic drugs: 3 (1-5); numbers of previous biological treatments: 2 (0-3), ABA as first line biological treatment: n=17).
T-cell characterization was performed by multi-color flow-cytometry (Navios, Beckman-Coulter).
At the end of our investigation, 28 patients discontinued ABA after 8 (4-16) months (18 for inefficacy; 5 for adverse events; 5 for other reasons) and 43 patients were still in therapy after 31 (13-62) months. In patients that maintained the treatment we observed: a lower proportion of smokers (25.6% vs 51.9%; p=0.03); a not significant lower proportion of ACPA positivity (76% vs 89.5%; p=0.13); a higher proportion of CD8+ terminally differentiated effector memory (TDEM) T-cells at baseline (38.7 (20.7-55.9) vs 22.0 (7.8-39.2) % of CD8+ T-cells; p=0.002). Other demographic, clinical and laboratory parameters were not different. Logistic multivariate analysis showed that only the proportion of CD8+TDEM T-cells was an independent predictive factor of high retention rate (OR (95% IC)=6.2 (1.2 to 30.8), p=0.026).
The ROC analysis showed a significant performance of this biomarker for prediction of persistence in therapy (using a cut-off of 30.6%: AUC: 0.760+0.07; p=0.002). patients with a high proportion of CD8+TDEM had a higher probability of continuing the treatment for a longer period of time (Mantel-Cox test: p<0.01). The positive and the negative predictive value of this test for treatment continuation were 83.3% and 65.0% respectively.
T-cell characterization for identification of TDEM CD8+ T-cells might be a useful test to predict persistence in therapy with ABA. It can be speculated that a high TDEM CD8+ T cell percentage might be a marker of previous repeated T-cell activation, identifying a subset of patients in which the CD28 costimulation blockade with ABA may be particularly efficacious.
To cite this abstract in AMA style:Piantoni S, Colombo E, Tincani A, Airò P, Scarsi M. Predictive Factors of Persistence in Therapy with Abatacept in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/predictive-factors-of-persistence-in-therapy-with-abatacept-in-patients-with-rheumatoid-arthritis/. Accessed March 23, 2023.
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