Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: T-cell profiles are heterogeneous between individuals and consist of naïve T cells, memory T cells (including effector memory T cells [TEM] and central memory T cells [TCM]) and short-lived or terminally differentiated effector cells (effector memory re-expressing CD45RA [TEMRA] cells).1 CD4 TEMRA cells (CD4+CD8–CD45RA+CD197–) vary in frequency and function, including distinct cytotoxic properties, between healthy individuals.2 However, their role in RA is unknown. The ongoing Phase IIIb Assessing Very Early Rheumatoid arthritis Treatment (AVERT)-2 trial (NCT02504268) aims to assess the efficacy and safety of abatacept (ABA) + MTX, vs ABA placebo (PBO) + MTX, in achieving clinical remission in DMARD-naïve adults with early RA, using stringent SDAI ≤3.3 criteria.3 We assessed the pharmacodynamic modulation of CD4 T-cell phenotypes and its association with ABA treatment (tx) response in AVERT-2.
Methods: AVERT-2 is a 132-week (wk), randomized, double-blinded study of ACPA+ and DMARD-naïve adults with RA diagnosis ≤6 months (ACR/EULAR 2010 criteria). Patients (pts) were randomized (3:2) to wkly SC ABA 125 mg + MTX vs ABA PBO + MTX for 56 wks (induction period [IP]) and then entered a 48-wk de-escalation period. Immune cell phenotyping via flow cytometry was performed on samples from a subset of pts in cohort 1 (all pts randomized who received ≥1 dose in the IP) through Wk 52. Data were analyzed using FlowJo® software. Estimates of adjusted mean change from baseline (BL) over time in CD4 T cells were from a repeated measures mixed model that included BL CD4 cell count, tx group, time and time-by-BL and time-by-tx group interaction. Changes over time were analyzed by whether pts achieved DAS28 (CRP) < 2.6 at Wk 52.
Results: Overall 58 pts who received ABA + MTX and 43 pts who received ABA PBO + MTX were included. BL demographics and disease characteristics at BL and Wk 52, between immune-cell–phenotyped and non-immune-cell–phenotyped cohorts, were comparable. BL DAS28 (CRP) scores were similar across these two cohorts for the ABA + MTX (5.80 vs 5.53, respectively) and ABA PBO + MTX (5.84 vs 5.58, respectively) tx arms. At the earliest time sampled (Month 1), a reduction in CD4 TEM and CD4 TEMRA cells was seen with ABA + MTX (Figure), which was sustained through Wk 52. Adjusted mean changes (95% CI) at Wk 52 with ABA + MTX vs ABA PBO + MTX were –6.0 (–8.6, –3.4) vs –2.0 (–5.3, 1.3) for TEM, and –1.6 (–2.4, –0.8) vs 0.5 (–0.5, 1.5) for TEMRA cells. Responders with DAS28 (CRP) < 2.6 at Wk 52 had greater reduction in these cell types with ABA + MTX vs ABA PBO + MTX (CD4 TEM: –6.5 [–10.2, –2.9] vs 4.2 [–2.8, 11.2]; CD4 TEMRA: (–2.9 [–4.0, –1.9] vs 1.2 [–0.4, 2.7]). This difference was not seen in non-responders. No association was observed with CD4 TCM cells between responders and non-responders.
Conclusion: Changes in CD4 TEM and CD4 TEMRA cells, probably suggestive of reduced proinflammatory immune response, were associated with abatacept response of DAS28 (CRP) < 2.6 in pts with seropositive RA.
1Thome JJ, et al. Cell 2014;159:814–28.
2Tian Y, et al. Nat Commun 2017;8:1473.
3Emery P, et al. Poster presented at ACR 2018:P563.
Professional medical writing: Joanna Wright, Caudex, funded by Bristol-Myers Squibb.
To cite this abstract in AMA style:Emery P, Tanaka Y, Bykerk V, Bingham C, Huizinga T, Citera G, Connolly S, Huang K, Elbez Y, Mukherjee S, Fleischmann R. Reduction in CD4 TEMRA Cells and Its Association with DAS28 (CRP) < 2.6 Treatment Response with Abatacept in Patients with Early, ACPA+, DMARD-Naïve RA [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/reduction-in-cd4-temra-cells-and-its-association-with-das28-crp-2-6-treatment-response-with-abatacept-in-patients-with-early-acpa-dmard-naive-ra/. Accessed August 3, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduction-in-cd4-temra-cells-and-its-association-with-das28-crp-2-6-treatment-response-with-abatacept-in-patients-with-early-acpa-dmard-naive-ra/