Session Information
Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose
ABCB1 (P-gp) and ABCG2 (BCRP) are part of the adenine triphosphate (ATP)-binding cassette (ABC) transporter proteins. These proteins mediate efflux of drugs from inside the cells and can confer a multidrug resistance phenotype. Since among its substrates are included drugs that are part of the treatment in Rheumatoid Arthritis (RA) such as prednisone and chloroquine (for ABCB1) and methotrexate and sulfasalazine (for ABCG2), these transporters might contribute to the resistance to treatment observed in some patients.
The objective of this study was to determine the activity of these transporters in patients with active and inactive rheumatoid arthritis.
Methods
We included patients with Rheumatoid Arthritis (2010 ACR/EULAR criteria) from the early rheumatoid arthritis cohort of our Institute. ABCB1 (P-gp) and ABCG2 (BCRP) functional activity was measured in peripheral mononuclear cells by flow cytometry. The percentage of cells able to extrude substrates for ABCB1 (daunorubicin) and ABCG2 (mitoxantrone) were recorded. The specificity of the assay was confirmed with specific inhibitors (verapamil for ABCB1 and KO143 for ABCG2). Thirty healthy controls were also evaluated to established normal values. The study was approved by our local ethics committee. For the statistical analysis continuous variables were compared with Student t or Mann-Whitney U tests and categorical variables with chi square or Fisher exact test as appropriate.
Results Thirty seven patients (all women) had been included. The mean age was 38.3 ± 12.3 years and a disease duration of 5 ± 3.3 years. Twenty patients had inactive and 17 active disease according to DAS28 (1.2 ± 1.5 vs 4.1 ± 1; p<0.001). There were no differences in age, disease duration or use of prednisone (76.5 vs 80%), methotrexate (94.1 vs 95%), antimalarials (41.2 vs 40%) or sulfasalazine (35.3 vs 25%) among active and inactive patients (respectively, all with p>0.05).
The median percentage value of cells able to extrude daunorubicin in active patients was 4.4% (IQR 0.7-19.7%) vs 0.9 (IQR 0.5-3.4) in inactive patients, while the median percentage of cells that extruded mitoxantrone in active patients was 1.7% (IQR 0.4-11.4%) vs 0.7% (IQR 0.4-1.8) in the inactive patients. These differences were no statistically significant.
Only 2 of 20 (10%) inactive patients were positive for ABCG2 and 8 of 17 (47%) active patients were positive (p=0.023) while for ABCB1 9/17 (53%) of active patients were positive and 6/20 (30%) of inactive patients were positive (p=0.157)
Conclusion Patients with active RA have a higher percentage of positivity for the ABCG2 transporter compared with those in remission independently of treatment and disease duration. Follow up of these patients is currently ongoing to determine if the functional activity of these efflux pumps entails a higher risk of persistent activity or risk of RA reactivation.
Disclosure:
Y. Atisha-Fregoso,
None;
H. Fragoso-Loyo,
None;
J. Jakez-Ocampo,
None;
G. Lima,
None;
M. Baños,
None;
V. Pascual-Ramos,
None;
I. Contreras-Yañez,
None;
L. Llorente,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/abcb1-and-abcg2-drug-efflux-transporters-function-and-its-association-with-disease-activity-in-a-cohort-of-patients-with-rheumatoid-arthritis/