Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial
Jeremy Sokolove, Michael Schiff, Roy Fleischmann, Michael E Weinblatt, Sean E Connolly, Alyssa Johnsen, Jin Zhu, Michael A Maldonado, Salil Patel, William H Robinson, Jeremy Sokolove, Michael Schiff, Roy Fleischmann, Michael E Weinblatt, Sean E Connolly, Alyssa Johnsen, Jin Zhu, Michael A Maldonado, Salil Patel, William H Robinson
Abstract
Objectives: To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study.
Methods: In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1-Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates.
Results: Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1-Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group.
Conclusions: In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab.
Trial registration number: NCT00929864.
Keywords: Ant-CCP; Autoantibodies; DMARDs (biologic); Rheumatoid Arthritis.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Figures
References
- Zendman AJ, van Venrooij WJ, Pruijn GJ. Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology (Oxford) 2006;45:20–5. 10.1093/rheumatology/kei111
- Aletaha D, Neogi T, Silman AJ, et al. . 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569–81. 10.1002/art.27584
- Nielen MM, van Schaardenburg D, Reesink HW, et al. . Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004;50:380–6. 10.1002/art.20018
- Sokolove J, Bromberg R, Deane KD, et al. . Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 2012;7:e35296 10.1371/journal.pone.0035296
- Willemze A, Trouw LA, Toes RE, et al. . The influence of ACPA status and characteristics on the course of RA. Nat Rev Rheumatol 2012;8:144–52. 10.1038/nrrheum.2011.204
- van der Helm-van Mil AH, Verpoort KN, Breedveld FC, et al. . Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 2005;7:R949–58. 10.1186/ar1767
- Ursum J, Bos WH, van Dillen N, et al. . Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study. Arthritis Res Ther 2010;12:R8 10.1186/ar2907
- Lv Q, Yin Y, Li X, et al. . The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis. PLoS ONE 2014;9:e89442 10.1371/journal.pone.0089442
- Pruijn GJ, Wiik A, van Venrooij WJ. The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis. Arthritis Res Ther 2010;12:203 10.1186/ar2903
- Schiff M, Weinblatt ME, Valente R, et al. . Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis 2014;73:86–94. 10.1136/annrheumdis-2013-203843
- Weinblatt ME, Schiff M, Valente R, et al. . Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: Findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum 2013;65:28–38. 10.1002/art.37711
- Pomirleanu C, Ancuta C, Miu S, et al. . A predictive model for remission and low disease activity in patients with established rheumatoid arthritis receiving TNF blockers. Clin Rheumatol 2013;32:665–70. 10.1007/s10067-012-2146-6
- Fisher BA, Plant D, Lundberg K, et al. . Heterogeneity of anticitrullinated peptide antibodies and response to anti-tumor necrosis factor agents in rheumatoid arthritis. J Rheumatol 2012;39:929–32. 10.3899/jrheum.111315
- Potter C, Hyrich KL, Tracey A, et al. . Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis. Ann Rheum Dis 2009;68:69–74. 10.1136/ard.2007.084715
- Bobbio-Pallavicini F, Caporali R, Alpini C, et al. . High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor alpha inhibitors in rheumatoid arthritis. Ann Rheum Dis 2007;66:302–7. 10.1136/ard.2006.060608
- Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. . The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006;54:1390–400. 10.1002/art.21778
- Gottenberg JE, Ravaud P, Bardin T, et al. . Positivity for RF/anti-CCP is associated with a better response to abatacept: data from the “Orencia and Rheumatoid Arthritis” (ORA) registry. Ann Rheum Dis 2011; 70(Suppl 3):74 10.1136/ard.2010.130278
- Gottenberg JE, Neto D, Gomez-Reino J, et al. . Positivity for rheumatoid factor and anti-cyclic citrullinated peptide is associated with better drug retention of abatacept: data from a pan-European analysis of RA registries. Ann Rheum Dis 2014;73(Suppl 2):502 10.1136/annrheumdis-2014-eular.5345
- Fujii T, Sekiguchi M, Matsui K, et al. . Very high titer of anti-citrullinated protein antibodies is associated with the achievement of clinical remission by abatacept in biologic-naïve patients with rheumatoid arthritis (the ABROAD study). Ann Rheum Dis 2013;72 (Suppl 3):889 10.1136/annrheumdis-2013-eular.2656
- Nüßlein H, Alten R, Galeazzi M, et al. . Two-year retention and effectiveness of IV abatacept in real-life setting: results from the ACTION study. Ann Rheum Dis 2014;73(Suppl 2):500 10.1136/annrheumdis-2014-eular.1750
Source: PubMed