ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1349

Two Composite Cytokine Scores Predict Flare and Drug-free Remission in Patients with Rheumatoid Arthritis

Jasmine Sim1, Nandhini Ramamoorthi2, Fiona Rayner3, Abbie Degnan1, Imogen Wilson1, Julie Diboll1, Anna Guttman4, Andrew Melville5, Nisha Rathore2, Stefan Siebert5, Iain McInnes6, Carl Goodyear5, Catharien Hilkens1, Andrew Filer7, Karim Raza7, Christopher Buckley8, Arthur Pratt1, James Wason9, Amy Anderson1, Michael Townsend2, Kenneth Baker1 and John Isaacs1, 1Translational and Clinical Research Institute, NIHR Newcastle Biomedical Research Centre, Newcastle University and The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom, 2Genentech, South San Francisco, CA, 3Translational and Clinical Research Institute, NIHR Newcastle Biomedical Research Centre, Newcastle University and The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, England, United Kingdom, 4Genentech, South San Franscisco, CA, 5School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 6University of Glasgow, College of Medical Veterinary and Life Sciences, Glasgow, United Kingdom, 7Rheumatology Research Group, Institute for Inflammation and Ageing, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Birmingham, United Kingdom, 8Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom, 9Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Meeting: ACR Convergence 2024

Keywords: , , ,

Session Information

Date: Sunday, November 17, 2024

Title: RA – Diagnosis, Manifestations, & Outcomes Poster II

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Recent studies show that half of patients with RA remission can stop conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy to achieve drug-free remission (DFR), although reliable methods to predict this remain elusive. We aimed to identify and validate circulating cytokine biomarkers that, when measured prior to csDMARD cessation, can predict future flare versus DFR.

Methods: Luminex immunoassays were used to quantify 19 circulating cytokines in serum and plasma samples from the BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE) study (discovery cohort: n = 114 patients) and the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) study (validation cohort: n = 41 patients) respectively. All patients in both studies fulfilled the 1987 ACR or 2010 ACR/EULAR classification criteria for RA diagnosis. Both studies followed the same intervention strategy: RA patients in remission, defined as a Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) < 2.4, stopped single or combination csDMARDs (methotrexate, sulfasalazine and hydroxychloroquine) and were monitored for 6 months. Flare was defined as DAS28-CRP ≥ 3.2 or DAS28-CRP ≥ 2.4 on 2 occasions within 14 days (BIO-FLARE); or DAS28-CRP ≥ 2.4 (BioRRA). Lasso regression was used to form composite cytokine scores that differentiated DFR and future flare, with prognostic performance assessed by area under the receiving operating characteristic curves (AUC).

Results: Two composite scores were developed to predict future flare and DFR in patients with or without anti-citrullinated peptide antibodies (ACPA). The composite score for seropositive RA included MMP-1, S100A8, and IL-6Ra, while TNF-a and IL-6Ra formed the predictive score for seronegative RA. In the discovery cohort, these two scores predicted future flare and DFR in ACPA+ and ACPA- patients with an AUC of 0.71 (95% confidence interval 0.59 – 0.83) and 0.76 (0.59 – 0.94) respectively. In the independent validation cohort, the same scores had an AUC of 0.72 (0.51 – 0.94) and 0.54 (0.24 – 0.83) respectively. If a strategy of drug cessation only in patients with below-threshold composite biomarker scores had been applied to both cohorts, 76/155 (49%) patients would have been eligible for stopping DMARDs with a lower overall flare rate (flare rate with biomarker 25/155 (16%) vs. 77/155 (50%) without biomarker; positive predictive value 65.8% [55.4 – 76.3], negative predictive value 67.1% [56.5 – 77.7]).

Conclusion: We present two validated composite cytokine scores that predict flare and DFR in patients with RA. Our next steps are to further validate our findings in an interventional clinical trial of drug cessation stratified by these biomarkers.

Supporting image 1

Baseline demographics of patients from the BIO-FLARE and BioRRA study. All values are expressed as median (interquartile range) [range] unless stated otherwise. All patients in both studies fulfilled the 1987 ACR or 2010 ACR/EULAR classification criteria for RA diagnosis. ACPA – Anti-citrullinated protein antibody, ACR – American College of Rheumatology, DAS28-CRP – Disease activity score in 28 joints with C-reactive protein, EULAR – European Alliance of Associations for Rheumatology, HCQ – Hydroxychloroquine, MTX – Methotrexate, RhF – Rheumatoid factor, SSZ – Sulfasalazine.

Supporting image 2

Strategy of applying the scores in a clinical setting prior to DMARD cessation, modelled in the BioRRA and BIO-FLARE cohorts (n = 155). Score A = 0.573[MMP_1] + 1.067[S100A8] + 0.844[IL6Rα], Score B = _1.318[TNFα] – 1.942[IL6Rα], where the natural log transformed cytokine concentrations were used to calculate the scores.

Disclosures: J. Sim: None; N. Ramamoorthi: Genentech, 3; F. Rayner: None; A. Degnan: None; I. Wilson: None; J. Diboll: None; A. Guttman: Genentech, 3; A. Melville: None; N. Rathore: Genentech, 3; S. Siebert: AbbVie, 6, Amgen, 6, AstraZeneca, 6, Boehringer-Ingelheim, 5, Bristol-Myers Squibb, 5, Eli Lilly, 5, GlaxoSmithKline, 5, Janssen, 5, 6, Teijin Pharma, 6, UCB, 5; I. McInnes: AbbVie, 2, 5, 6, Amgen, 2, Bristol Myers Squibb, 2, 5, Cabaletta, 2, Celgene, 2, Compugen, 2, Dextera, 2, Eli Lilly, 2, 5, Janssen, 2, 5, Moonlake, 2, Novartis, 2, 5, Pfizer, 2, UCB, 2, 5, 6; C. Goodyear: None; C. Hilkens: None; A. Filer: None; K. Raza: None; C. Buckley: None; A. Pratt: Gilead, 5, GlaxoSmithKlein(GSK), 5, Inflection Biosciences, 2; J. Wason: None; A. Anderson: None; M. Townsend: Genentech, 3; K. Baker: Pfizer, 5; J. Isaacs: AbbVie/Abbott, 2, 6, AnaptysBio, 2, Annexon, 2, AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2, Dragonfly, 2, Eli Lilly, 1, Galapagos, 2, GlaxoSmithKlein(GSK), 2, 5, Istesso, 2, Janssen, 5, Kira Biotech, 2, Ono Pharma, 2, Pfizer, 5, Revelo, 2, Sanofi, 2, Sonoma Biotherapeutics, 2, Topas, 2, UCB, 1.

To cite this abstract in AMA style:

Sim J, Ramamoorthi N, Rayner F, Degnan A, Wilson I, Diboll J, Guttman A, Melville A, Rathore N, Siebert S, McInnes I, Goodyear C, Hilkens C, Filer A, Raza K, Buckley C, Pratt A, Wason J, Anderson A, Townsend M, Baker K, Isaacs J. Two Composite Cytokine Scores Predict Flare and Drug-free Remission in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/two-composite-cytokine-scores-predict-flare-and-drug-free-remission-in-patients-with-rheumatoid-arthritis/. Accessed .

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