Baseline autoantibodies preferentially impact abatacept efficacy in patients with rheumatoid arthritis who are biologic naïve: 6-month results from a real-world, international, prospective study

Rieke Alten, Hubert G Nüßlein, Xavier Mariette, Mauro Galeazzi, Hanns-Martin Lorenz, Alain Cantagrel, Melanie Chartier, Coralie Poncet, Christiane Rauch, Manuela Le Bars, Rieke Alten, Hubert G Nüßlein, Xavier Mariette, Mauro Galeazzi, Hanns-Martin Lorenz, Alain Cantagrel, Melanie Chartier, Coralie Poncet, Christiane Rauch, Manuela Le Bars

Abstract

Objectives: To determine the impact of baseline rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) status on the clinical efficacy of intravenous abatacept in biologic-naïve patients with rheumatoid arthritis (RA) enrolled in the real-world ACTION study.

Methods: Clinical outcomes (European League Against Rheumatism (EULAR) response, mean Clinical Disease Activity Index (CDAI) and Boolean remission) at 6 months were compared by baseline RF and anti-CCP status.

Results: Of 672 biologic-naïve patients, RF status was reported in 577 (86%) (412 (71%) positive) and anti-CCP status in 552 (82%) (364 (66%) positive); of 511 patients for whom data were available, 308/511 (60%) were double positive and 127/511 (25%) were double negative. Clinical outcomes were improved with RF-positive or anti-CCP-positive versus RF-negative/anti-CCP-negative status-good or moderate EULAR response: RF: 84.6 vs 72.9%, p=0.012; anti-CCP: 85.2 vs 74.2%, p=0.015; mean CDAI (calculated): RF: 10.8 vs 15.3, p<0.001; anti-CCP: 10.9 vs 14.3, p=0.002; and Boolean remission: RF: 13.3 vs 4.0%, p=0.008; anti-CCP: 12.5 vs 6.3%, p=0.096. Clinical outcomes were also improved with single or double RF-positive/anti-CCP-positive versus double-negative status.

Conclusions: In biologic-naïve patients with RA, RF-positive and/or anti-CCP-positive status is associated with greater efficacy of intravenous abatacept than seronegative status.

Trial registration number: NCT02109666.

Keywords: Ant-CCP; Rheumatoid Arthritis; Rheumatoid Factor.

Conflict of interest statement

Competing interests: RA has received research grants and consulting fees and is on a speaker bureau for Bristol-Myers Squibb. HGN is a consultant for Bristol-Myers Squibb, Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis and Roche and is on speaker bureaus for Bristol-Myers Squibb, Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis and Roche. MG has no competing interests to disclose. XM is on speaker bureaus for Bristol-Myers Squibb, GSK, Pfizer and UCB. H-ML is a consultant for AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer and Actelion, and is on speaker bureaus for AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer and Actelion. AC has received research grants from UCB and Pfizer, and consultant fees from AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer and Roche. MC is an employee of Bristol-Myers Squibb. CP is a consultant for Bristol-Myers Squibb. CR is a shareholder and employee of Bristol-Myers Squibb. MLB is a shareholder and employee of Bristol-Myers Squibb.

Figures

Figure 1
Figure 1
(A) EULAR response based on DAS28 (ESR, otherwise CRP) and (B) Boolean remission, at 6 months in patients treated with abatacept as a first-line biologic by RF or anti-CCP seropositivity* alone or combined. p Value for likelihood of a good/moderate EULAR response versus no response based on DAS28 (ESR, otherwise CRP). Error bars represent 95% CI. *Derived DAS28 based on core components. CCP, cyclic citrullinated peptide; CRP, C reactive protein; DAS28, Disease Activity Score in 28 joints; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; RF, rheumatoid factor.

References

    1. Orencia (250 mg powder for concentrate for solution for infusion) Summary of Product Characteristics. (accessed 10 Sep 2015).
    1. Orencia prescribing information. (accessed 18 May 2016).
    1. 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
    1. Unger M, Alasti F, Studenic P et al. . Are changes in autoantibody levels reflecting change in prognosis of rheumatoid arthritis? Arthritis Rheumatol 2015;67(Suppl 10):1–4046.
    1. 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
    1. Sokolove J, Schiff M, Fleischmann R et al. . Impact of baseline anti-cyclic citrullinated peptide 2 antibody titre on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis 2015;74:983–4.
    1. 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
    1. Gottenberg JE, Ravaud P, Cantagrel A et al. . Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the ‘Orencia and Rheumatoid Arthritis’ registry. Ann Rheum Dis 2012;71:1815–19. 10.1136/annrheumdis-2011-201109
    1. Gottenberg JE, Courvoisier DS, Hernandez MV et al. . Brief report: association of rheumatoid factor and anti-citrullinated protein antibody positivity with better effectiveness of abatacept: results from the pan-European registry analysis. Ann Rheum Dis 2016;68:1346–52. 10.1002/art.39595
    1. Isaacs JD, Cohen SB, Emery P et al. . Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis 2013;72:329–36. 10.1136/annrheumdis-2011-201117
    1. Nüßlein HG, Alten R, Galeazzi M et al. . Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year, observational, prospective ACTION study. BMC Musculoskelet Disord 2014;15:14 10.1186/1471-2474-15-14
    1. Harigai M, Ishiguro N, Inokuma S et al. . Postmarketing surveillance of the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis. Mod Rheumatol 2016;8:1–8.
    1. Arnett FC, Edworthy SM, Bloch DA et al. . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24. 10.1002/art.1780310302
    1. Huizinga TWJ, Connolly SE, Johnsen A et al. . Effect of anti-cyclic citrullinated peptide 2 immunoglobulin M serostatus on efficacy outcomes following treatment with abatacept plus methotrexate in the AVERT trial. Ann Rheum Dis 2015;74(Suppl 2):234.
    1. Platt AM, Gibson VB, Patakas A et al. . Abatacept limits breach of self-tolerance in a murine model of arthritis via effects on the generation of T follicular helper cells. J Immunol 2010;185:1558–67. 10.4049/jimmunol.1001311
    1. U.S. Food and Drug Administration, Department of Health and Human Services. International Conference on Harmonisation; Good Clinical Practice: Consolidated Guideline; Availability. Federal Register 1997;62:25692–709.
    1. Olsen J. Good Epidemiological Practice (GEP): IEA Guidelines for Proper Conduct in Epidemiological Research. (accessed 25 May 2016).

Source: PubMed

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