Unraveling Heterogeneity Within ACPA-negative Rheumatoid Arthritis; The Subgroup of Patients with a Strong Clinical and Serological Response to Initiation of DMARD-treatment Favor Disease Resolution

Marloes Verstappen¹, Hanna van Steenbergen², Pascal de Jong³ and Annette H.M van der Helm-van Mil¹, ¹Leiden University Medical Center, Leiden, Netherlands, ²Leiden Univeristy Medical Center, Leiden, Netherlands, ³Erasmus MC, Hendrik Ido Ambacht, Netherlands

Meeting: ACR Convergence 2021

Keywords: Anti-citrullinated Protein Autoantibodies (ACPAs), Biomarkers, Disease-Modifying Antirheumatic Drugs (Dmards), rheumatoid arthritis

Session Information

Date: Sunday, November 7, 2021

Session Title: RA – Diagnosis, Manifestations, & Outcomes Poster II: Miscellaneous Aspects of RA (0786–0812)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Rheumatoid arthritis (RA) is a heterogeneous disease, especially ACPA-negative-RA. This is reflected by differences in long-term outcomes, ranging from refractory RA to sustained-DMARD-free-remission(SDFR; sustained absence of synovitis after DMARD-cessation). Differentiation of RA-patients who are most likely to achieve SDFR can contribute to personalized treatment and tapering-strategies, however this subgroup remains scarcely discerned. Previous research demonstrated that RA-patients achieving SDFR are characterized by an early clinical response (DAS-remission after 4-months) after DMARD-start. We studied whether, in addition to this clinical response, a specific biomarker-response can further differentiate the subgroup of RA-patients most likely to achieve SDFR.

Methods: In 266 RA-patients, levels of 12-biomarkers(SAA/CRP/MMP-1/MMP-3/resistin/leptin/IL-6/TNF-R1/YKL-40/EGF/VEGF/VCAM-1) in the first 2-years after diagnosis, were studied in relation to SDFR, stratified for ACPA-status. Subsequently, biomarkers associated with SDFR-development were combined with early DAS-remission to study its additional value in defining subgroups. Since most biomarker-levels are not routinely measured in clinical practice, we explored how this subgroup could be recognized.

Results: ACPA-negative-RA-patients achieving SDFR(n=63) were characterized by a stronger decline in MMP-1/MMP-3/SAA/CRP 1-year after DMARD-start; respectively 1.30x/1.44x/2.12x/2.24x stronger. This effect was absent in ACPA-positive-RA. In ACPA-negative-RA, a strong biomarker-decline associated with early DAS-remission and the combination of both declines was present in a subgroup of ACPA-negative RA-patients achieving SDFR. This subgroup can be clinically recognized by the combination of high baseline CRP-levels(≥3-times ULN), and early DAS-remission (DAS_4-months< 1.6).

Conclusion: ACPA-negative RA-patients with early DAS-remission and a strong biomarker-response (or baseline CRP-levels≥3xULN) are most likely to achieve SDFR later-on. This could guide personalized treatment-decisions on DMARD-tapering/cessation in ACPA-negative-RA.

Disclosures: M. Verstappen, None; H. van Steenbergen, None; P. de Jong, None; A. van der Helm-van Mil, None.

To cite this abstract in AMA style:

Verstappen M, van Steenbergen H, de Jong P, van der Helm-van Mil A. Unraveling Heterogeneity Within ACPA-negative Rheumatoid Arthritis; The Subgroup of Patients with a Strong Clinical and Serological Response to Initiation of DMARD-treatment Favor Disease Resolution [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/unraveling-heterogeneity-within-acpa-negative-rheumatoid-arthritis-the-subgroup-of-patients-with-a-strong-clinical-and-serological-response-to-initiation-of-dmard-treatment-favor-disease-resolution/. Accessed February 6, 2023.

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