AB0220 ANTI-CITRULLINATED PROTEIN ANTIBODY (ACPA) POSITIVITY IS ASSOCIATED WITH REDUCED WITHDRAWAL RATES OF ABATACEPT IN RHEUMATOID ARTHRITIS BUT ONLY IN PATIENTS WHO ARE ANTI-NUCLEAR ANTIBODY (ANA) NEGATIVE
Authors: J. Kimpton, M. Shipa, E. Hawkins, S. A. Yeoh, M. Greenwood, M. Ehrenstein
Journal: Annals of the Rheumatic Diseases (2021)

Background: Abatacept, a selective inhibitor of T cell co-stimulation, is often used as a second-line biologic disease-modifying anti-rheumatic drug (bDMARD) after the failure of tumour necrosis factor inhibitor (TNFi) in Rheumatoid Arthritis (RA). However, in comparison to TNFi very few survival analyses of abatacept have been reported. 1,2 Objectives: To investigate predictors of abatacept discontinuation due to either inefficacy or adverse events in RA patients over 5-years. Methods: A retrospective observational analysis was conducted on a tertiary hospital dataset of RA (according to 2010 ACR/EULAR criteria) patients who started abatacept (either intravenous or subcutaneous). Time to abatacept discontinuation over 5-years was estimated using Kaplan-Meier survival analyses. A multivariate cox-regression model to predict abatacept discontinuation was chosen by elastic net regularisation. Results: A total of 112 patients with RA [81% female, mean age 58.1 (SD 13.5) years] commenced abatacept therapy during the study period. 88 (78.6%) patients received intravenous abatacept, 14 (15.9%) of whom switched to subcutaneous injection, and 24 (21.4%) were initially treated with subcutaneous abatacept, 2 (8.3%) of whom switched to intravenous. More than half of the patients (65/112) were treated with at least one concomitant conventional synthetic DMARD (csDMARD). Methotrexate was the most commonly used (n = 37) csDMARD, followed by hydroxychloroquine (n = 23), sulfasalazine (n= 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (either oral, intra-articular, or intramuscular injection) during the time they were treated with abatacept. Abatacept was most commonly used as 4th (n = 29) and 3rd line (n = 24) bDMARD but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive in 32 patients. Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years. Multivariate cox regression (variables chosen by the elastic net and adjusted by whether or not abatacept was used as first-line therapy) showed that ACPA positivity was associated with a reduced risk of abatacept discontinuation with a hazard ratio (HR) of 0.40 (95% CI 0.18 to 0.85, p=0.02, N. of events 16/47) compared to ACPA negative patients (N. of events 15/23), but only if ANA was negative. In contrast, ACPA positivity did not reveal any retention benefit over ACPA negative patients, if they were ANA positive. ACPA positive patients without positive ANA increased the time-to-discontinuation of abatacept predominantly after 3-months (unadjusted log-rank p=0.02), compared to ACPA, and ANA negative patients (Figure 1). Adding csDMARDs with abatacept, reduced the risk of discontinuation of abatacept by 59% (95% CI 24% to 77%, p = 0.004, N. of events 26/65) compared to monotherapy (N. of events 28/47). Conclusion: Our data suggests patients who are ACPA positive and ANA negative are more likely to remain on abatacept therapy. Concomitant csDMARD use also acts as a positive predictor of abatacept treatment retention. References: [1]Cagnotto G, et al. Arthritis Res Ther. 2020;22(1):15. [2]Alten R, et al. Clin Rheumatol. 2019;38(5):1413-1424. Figure 1. Kaplan-Meier survival curve of retention of abatacept, stratified by Anti-citrullinated protein antibody (ACPA) and antinuclear antibody (ANA). +ACPA/-ANA = ACPA positive and ANA negative , +ACPA/+ANA = ACPA positive and ANA positive , -ACPA/-ANA = ACPA negative and ANA negative , -ACPA/+ANA = ACPA negative and ANA positive , HR = Hazard ratio. Acknowledgements: I have no acknowledgements to declare. Disclosure of Interests: None declared