POS0474 SUBSTANTIAL IMPACT OF AUTOANTIBODY ENRICHMENT ON OUTCOMES IN EARLY RHEUMATOID ARTHRITIS TREATED WITH ABATACEPT: DATA FROM A LARGE POOLED ANALYSIS OF 4 RCTS
Authors: K. Michaud, S. S. H. Park, K. Lozenski, J. Vaile, V. Khaychuk, J. Pope, P. G. Conaghan
Journal: Annals of the Rheumatic Diseases (2021)

Background: Biomarkers are commonly used as prognostic tools in rheumatoid arthritis (RA) and have additional potential to guide treatment decisions. Previous clinical trials of abatacept (ABA) such as the Early AMPLE trial (eAMPLE) and real-world data suggest differential treatment effects of ABA based on the presence of biomarkers and disease stage. 1-4 Objectives: To supplement evidence of enhanced efficacy of ABA among patients with enriched autoantibody biomarkers and early disease stage by applying key inclusion criteria from the eAMPLE trial retrospectively to historic ABA RCTs. Methods: Individual patient data (IPD) from four early-RA ABA trials (AGREE [ NCT00122382 ], AMPLE [ NCT00929864 ], AVERT [ NCT01142726 ], AVERT-2 [ NCT02504268 ]) were pooled. Patients were defined as enriched at baseline if they had: 1) RA disease duration ≤ 12 months, 2) DAS28-CRP ≥ 3.2, 3) ≥ 3 times the upper limit of normal on an anti-cyclic citrullinated peptide (anti-CCP) test, and 4) were rheumatoid factor positive (RF+). Patients were grouped according to treatment status (ABA [monotherapy or with methotrexate (MTX)] or non-ABA [MTX or adalimumab (ADA) plus MTX]). Outcomes included DAS28-CRP mean change from baseline to week 24, DAS28-CRP remission and ACR 20/50/70 at week 24. IPD mixed-effects meta-regressions were estimated with trial fixed effects, main effects and interaction of enrichment status and treatment type, trial-level random effects on the interaction, and baseline DAS28-CRP score for DAS28-CRP outcomes. These regressions were conducted in the full population and among ABA patients only. Sensitivity analyses defining enrichment using only criteria 3 and 4 were also conducted. Results: 2,087 patients [1,328 (64%) enriched, 759 (36%) non-enriched] were included (AGREE 492 [24%], AMPLE 509 [24%], AVERT 339 [16%], AVERT-2 747 [36%]). Disease duration, RF+, and anti-CCP values differed as expected between the two groups, while DAS28-CRP was high regardless of enrichment status (Table 1). Among ABA-treated patients, outcomes were more favorable for enriched patients compared to non-enriched patients across all outcomes, either statistically or directionally (Figure 1, ABA treatment arm only analysis). The differences in outcomes between enriched vs. non-enriched patients were larger for ABA than for comparators across all outcomes with the exception of ACR 50, where the difference was directionally consistent (Figure 1, ABA vs. comparator analysis). The relative odds of improved efficacy of ABA vs. comparators ranged from 37% to 87% for remission and ACR responses. The results were consistent in the sensitivity analysis using only anti-CCP and RF seropositivity to define enrichment. Figure 1. Analysis results Conclusion: This post-hoc study corroborates previous evidence of improved outcomes among ABA-treated, seropositive early RA patients by applying eAMPLE inclusion criteria retrospectively to ABA RCTs. The findings support a differential treatment effect for costimulation blockade using ABA among enriched and double antibody positive early RA patients, suggesting a potential for patient-tailored RA treatment approaches. References: [1]Buckner J, et al. Arthritis Rheumatol. 2019; 71 (suppl 10). [2]Huizinga T, et al Annals of the Rheumatic Diseases 2015;74:234-235. [3]Harrold L, et al, Rheumatol Ther. 2019 Jun;6(2):217-230. [4]Sokolove J, et al. Ann Rheum Dis 2016 Apr;75:709–714. Table 1. Baseline characteristics All patients Non-enriched patients Enriched patients Abatacept Comparators Abatacept Comparators N = 2,087 N = 385 N = 374 N = 784 N = 544 Demographics Age (years) 49.3 ± 12.9 49.4 ± 12.6 50.6 ± 12.9 48.6 ± 12.5 49.2 ± 13.5 Female 79.3% 81.3% 83.4% 77.2% 77.9% Disease characteristics Disease duration (months) 8.5 ± 12.5 19.9 ± 15.9 18.3 ± 15.1 2.4 ± 2.8 2.4 ± 2.9 RF Positive 91.0% 74.2% 76.1% 100% 100% Anti-CCP Positive 81.8% 52.2% 47.3% 100% 100% DAS28-CRP Score 5.71 ± 1.13 5.72 ± 1.19 5.66 ± 1.20 5.68 ± 1.09 5.76 ± 1.08 Comparators included MTX and MTX+ADA. Acknowledgements: This study was sponsored by Bristol Myers Squibb. Disclosure of Interests: Kaleb Michaud Grant/research support from: Pfizer Aspire grant, Sarah (Sang Hee) Park Employee of: Bristol Myers Squibb, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, John Vaile Shareholder of: Amgen, Novartis, Bristol Myers Squibb, Regeneron, Employee of: Bristol Myers Squibb, Vadim Khaychuk Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Janet Pope Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, BI, Gilead, Galapagos, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Sanofi, Sandoz, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, BI, Celltrion, Gilead, Galapagos, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Samsung, Sanofi, Sandoz, Teva, UCB, Grant/research support from: AbbVie, BMS, Merck, Pfizer, Roche, Seattle Genetics, Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: Bristol Myers Squibb, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer