BASELINE IL-10 LEVELS AS A PREDICTIVE BIOMARKER FOR ACHIEVING CLINICAL RESPONSE WITH ABATACEPT IN ACPA+ PATIENTS WITH EARLY RA

Background: A key target of RA treatment is to achieve early and sustained remission in order to ensure lower levels of long-term structural joint damage and physical disability. Identifying predictive biomarkers may help guide treatment options to achieve this. Inflammatory biomarkers such as IL-10, a pleiotropic cytokine that drives B-cell responses and is associated with higher seropositivity for RF and anti-CCP in patients with RA,[1] may provide predictive clinical value. Objectives: We evaluated the association of baseline (BL) circulated biomarkers with disease activity (DA) measures and their ability to predict clinical response in MTX-naive, ACPA+ patients with early RA from a phase 3b study (AVERT-2; NCT02504268).[2] Methods: Patients aged ≥ 18 years with early RA (≤ 6 months from diagnosis; ACR/EULAR 2010 [3]) were randomized to abatacept + MTX or abatacept placebo + MTX (referred to as MTX). Serum samples were collected over a 56-week period, with endpoints assessed at weeks 24 and 52. A broad selection of 113 inflammatory and immune response–related proteins were analyzed using either the Olink Target 96 multiplex immunoassay inflammation panel or selected panels from Myriad Rules-Based Medicine. The association of BL biomarkers and clinical DA measures were analyzed using Spearman’s correlation, with changes from BL in all biomarkers analyzed via repeated measures mixed-effects models. Logistic regression modeling was utilized to investigate predictive biomarkers with BL age, Simplified Disease Activity Index (SDAI), pain (measured via visual assessment scale), and ACPA positivity as covariates. Results: Of 752 patients in the intent-to-treat population, 446 from the abatacept + MTX arm and 300 from the MTX arm were included in the biomarker analyses. BL patient characteristics were well balanced between treatments. There were 15 biomarkers significantly associated with ≥ 2 BL DA measures at baseline; patients receiving abatacept + MTX showed significantly greater reductions in all 15 biomarkers compared with MTX ( P < 0.05 to P < 0.001), with a change from BL in 13 of the 15 biomarkers demonstrating significant associations with DA measure reduction ( P < 0.05). Higher BL levels of IL-10 predicted greater clinical improvement, assessed by ACR and DAS28 (CRP) (< 2.6) responses and SDAI remission (≤ 3.3), with abatacept + MTX vs MTX ( P < 0.03 to P < 0.0007 at week 52) (Figure 1). Further, a higher BL IL-10 concentration tertile was significantly associated with greater improvements in DAS28 (CRP) and SDAI on abatacept + MTX vs MTX ( P < 0.05 to P < 0.001 at days 29–365) (Figure 2). Conclusion: Higher BL IL-10 levels predicted greater clinical response for patients treated with abatacept + MTX vs MTX. Increased IL-10 levels may reflect greater interactions between CD4+ T-helper cells and autoantibody-producing B cells. These findings may help clinicians to identify patients most likely to respond favourably to the abatacept mechanism of action and with poor response to MTX single therapy. A prospective study is warranted to confirm whether screening for IL-10 in the clinical setting can help guide treatment options for patients with RA. REFERENCES: [1] Hernández-Bello J, et al. Cytokine 2017;95:88–96. [2] Emery P, et al. Rheumatol Ther 2023;10:707–727. [3] Aletaha D, et al. Arthritis Rheum 2010;62:2569–2581. Acknowledgements: Lauren McDonagh (Caudex, a division of IPG Health Medical Communications), funded by Bristol Myers Squibb. Disclosure of Interests: Jinqi Liu Bristol Myers Squibb, Bristol Myers Squibb, Yicong Li Bristol Myers Squibb (contractor), Kai Fu Bristol Myers Squibb, Chun Wu Bristol Myers Squibb, Bristol Myers Squibb, Peter Schafer Bristol Myers Squibb, Bristol Myers Squibb, Sean Connolly Bristol Myers Squibb, Bristol Myers Squibb, Ian M. Catlett Bristol Myers Squibb, Bristol Myers Squibb, Michael A. Maldonado Bristol Myers Squibb, Bristol Myers Squibb, Robert Wong Since my retirement from Bristol Myers Squibb in 2022, I receive no shares of Bristol Myers Squibb. I have pre-existing shares from my employment., I was a former employee of Bristol Myer’s Squibb (BMS) from 2010-2022. I retired from BMS in January 2022 and have had no affiliation with BMS since then., Paul Emery AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, Janssen, MSD, Lilly, Novartis, Pfizer, Roche, Samsung, AbbVie, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche, Samsung, Yoshiya Tanaka AbbVie, Asahi Kasei, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb,Chugai, Eisai, Gilead, GlaxoSmithKline, Lilly, Pfizer, Taiho, Asahi Kasei, Chugai, Eisai, Mitsubishi-Tanabe, Taiho, Vivian Bykerk Bristol Myers Squibb, Pfizer, Clifton O. Bingham AbbVie, Bristol Myers Squibb, Janssen, Lilly, Sanofi, Bristol Myers Squibb, Tom Huizinga Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Lilly, Nycomed, Pfizer, Roche, Abblynx, Abbott, Biotest AG, Boehringer Ingelheim, Bristol Myers Squibb, Crescendo Bioscience, Epirus, Galapagos, Janssen, Lilly, Merck, Novartis, Nycomed, Pfizer, Roche, Sanofi-Aventis, Takeda, UCB, Zydus, AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, Roy Fleischmann AbbVie, Arthrosi, Bristol Myers Squibb, Galvani, GlaxoSmithKline, Immunovant, Janssen, Lilly, Novartis, Pfizer, Recor, Vyne, AbbVie, Arthrosi, Bristol Myers Squibb, Galvani, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer DOI: 10.1136/annrheumdis-2024-eular.118 Keywords: Clinical Trial, Outcome measures, Biomarkers, Cytokines and Chemokines Citation: , volume 83, supplement 1, year 2024, page 750Session: Rheumatoid arthritis (Poster View)

Clinical Trial, Outcome measures, Biomarkers, Cytokines and Chemokines