Session Type: Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: ACPAs are sensitive, highly specific markers of RA. Current tests cannot differentiate ACPA+ RA subtypes. Fine-specificity ACPAs (FS) can distinguish between ACPA+ RA subtypes to explore predictors of treatment (tmt) response. Higher vs lower baseline (BL) ACPA levels have been associated with improved response to abatacept (ABA).1 In the Phase IIIb AVERT study, ABA + MTX was more effective than MTX in early RA: 61% vs 45% of patients (pts) achieved DAS28 (CRP) remission (< 2.6) at 12 mths.2 We investigated FS as biomarkers to predict tmt response in pts with seropositive RA in AVERT.
Methods: Pts in AVERT (NCT01142726) were randomized to double-blind weekly SC ABA 125 mg + MTX, SC ABA 125 mg or MTX for 12 mths. In this post hoc analysis, predictive value of 29 BL FS and 10 non-citrullinated control antibodies (Ab) for efficacy measures (DAS28 [CRP], SDAI) was explored using logistic or linear regression models for remission rates (RR; SDAI remission ≤3.3) and change from BL (CfB) outcomes, respectively, with tmt arm, BL disease activity, age, sex, prior CS use, BL FS (continuous or categorized into tertiles [T; specific for each FS and control Ab]) and FS-by-tmt arm interaction as covariates. Linear mixed-effects model with repeated measures was used for time series analysis. Pairwise comparisons (unadjusted p values) between tmt arms were performed for DAS28 (CRP) and SDAI RR or adjusted mean CfB in each T. FS were analyzed with custom Bio-PlexTM bead-based autoantibody assay.3
Results: BL characteristics were comparable in overall (N=351) and target biomarker (n=340) populations and across tmt arms (not shown). Of 29 BL FS, 15 significantly correlated with anti-CCP Ab (ACCP; surrogate of ACPA). Of 29 FS or ACCP, higher BL anti-fibrinogen B 62–81 cit 74 (ABA + MTX p=0.017; MTX p=0.99) and ACCP (ABA + MTX p=0.018; MTX p=0.89) levels were significantly associated with higher probability of DAS28 (CRP) remission in pts who received ABA + MTX but not MTX (Figure 1); levels of non-citrullinated control anti-fibrinogen B 62–81 did not correlate with tmt response (p=0.324). For DAS28 (CRP) RR, tmt differences (ABA + MTX vs MTX) were greater in medium (T2) and high (T3) subgroups vs overall population: ACCP (T2; p≤0.01), 28%; anti-fibrinogen B 62-81 cit 74 (T3; p≤0.01), 32%; overall population, 16% (Figure 2). Tmt differences in adjusted mean DAS28 (CRP) CfB for ABA + MTX vs MTX and ABA vs MTX were greater in medium (T2; Mth 6) and high (T3; Mths 6, 12) vs low (T1) anti-fibrinogen B 62–81 cit 74 subgroups (Figure 3); similar findings were seen for SDAI. Anti-fibrinogen B 62–81 cit 74 (vs ACCP) better predicted DAS28 (CRP) CfB improvement with ABA + MTX vs MTX (not shown).
Conclusion: BL FS predicted improved DAS28 (CRP), SDAI RR and CfB with abatacept + MTX vs MTX; higher BL T showed greater differentiation in tmt response with abatacept + MTX vs MTX. Anti-fibrinogen B 62–81 cit 74 (vs ACCP) better predicted DAS28 (CRP) improvement with abatacept + MTX vs MTX. These data support anti-fibrinogen B 62–81 cit 74 as a predictor of tmt response to abatacept.
- Sokolove J, et al. Ann Rheum Dis 2016;75:709–714.
- Emery P, et al. Ann Rheum Dis 2015;74:19–26.
- Wagner CA, et al. Ann Rheum Dis 2015;74:579–586.
Medical writing: Katerina Kumpan (Caudex).
To cite this abstract in AMA style:Robinson W, Wu C, Hu S, Connolly S, Mukherjee S. Higher Baseline Fine-Specificity ACPAs Predict Greater Treatment Response with Abatacept + MTX versus MTX Monotherapy in Seropositive RA: A Post Hoc Analysis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/higher-baseline-fine-specificity-acpas-predict-greater-treatment-response-with-abatacept-mtx-versus-mtx-monotherapy-in-seropositive-ra-a-post-hoc-analysis/. Accessed November 26, 2020.
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