Top

Published in:

Open Access 25-05-2023 | Abatacept | Original Research

Benefits of Autoantibody Enrichment in Early Rheumatoid Arthritis: Analysis of Efficacy Outcomes in Four Pooled Abatacept Trials

Authors: Kaleb Michaud, Philip G. Conaghan, Sang Hee Park, Karissa Lozenski, Mirko Fillbrunn, Vadim Khaychuk, Elyse Swallow, John Vaile, Henry Lane, Ha Nguyen, Janet Pope

Published in: Rheumatology and Therapy | Issue 4/2023

Abstract

Introduction

The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients.

Methods

Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration < 1 year, and Disease Activity Score-28 (DAS28) C-reactive protein (CRP) ≥ 3.2 at baseline; non-SPEAR otherwise. Outcomes included: American College of Rheumatology (ACR) 20/50/70 at week 24; mean change from baseline to week 24 for DAS28 (CRP), Simple Disease Activity Index (SDAI), ACR core components; DAS28 (CRP) and SDAI remission. Adjusted regression analyses among abatacept-treated patients compared SPEAR and non-SPEAR patients, and in full trial population estimating how the efficacy of abatacept versus comparators [adalimumab + methotrexate, methotrexate] was modified by SPEAR status.

Results

The study included 1400 SPEAR and 673 non-SPEAR patients; most were female (79.35%), white (77.38%), and with a mean age 49.26 (SD 12.86) years old. Around half with non-SPEAR were RF + and three-quarters ACPA +. Stronger improvements from baseline to week 24 were observed in almost all outcomes for abatacept-treated SPEAR versus non-SPEAR patients or versus SPEAR patients treated with comparators. Larger improvements were observed for SPEAR patients among the abatacept-treated population, and more strongly improved efficacy among SPEAR patients for abatacept than comparators.

Conclusions

This analysis, including large patient numbers of early-RA abatacept trials, confirmed beneficial treatment effects of abatacept in patients with SPEAR versus non-SPEAR.

Shams S, Martinez JM, Dawson JRD, et al. The therapeutic landscape of rheumatoid arthritis: current state and future directions. Front Pharmacol. 2021;12: 680043. https://doi.org/10.3389/fphar.2021.680043.CrossRefPubMedPubMedCentral

Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360–72. https://doi.org/10.1001/jama.2018.13103.CrossRefPubMed

Uhlig T, Moe RH, Kvien TK. The burden of disease in rheumatoid arthritis. Pharmacoeconomics. 2014;32(9):841–51. https://doi.org/10.1007/s40273-014-0174-6.CrossRefPubMed

Myasoedova E, Crowson CS, Kremers HM, et al. Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum. 2010;62(6):1576–82. https://doi.org/10.1002/art.27425.CrossRefPubMedPubMedCentral

Tobon GJ, Youinou P, Saraux A. The environment, geo-epidemiology, and autoimmune disease: rheumatoid arthritis. J Autoimmun. 2010;35(1):10–4. https://doi.org/10.1016/j.jaut.2009.12.009.CrossRefPubMed

Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;8(4):18001. https://doi.org/10.1038/nrdp.2018.1.CrossRef

Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924–39. https://doi.org/10.1002/acr.24596.CrossRefPubMed

Katchamart W, Koolvisoot A, Aromdee E, et al. Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis. Rheumatol Int. 2015;35(10):1693–9. https://doi.org/10.1007/s00296-015-3271-8.CrossRefPubMed

Trouw LA, Mahler M. Closing the serological gap: promising novel biomarkers for the early diagnosis of rheumatoid arthritis. Autoimmun Rev. 2012;12(2):318–22. https://doi.org/10.1016/j.autrev.2012.05.007.CrossRefPubMed

10.

Wiik AS, van Venrooij WJ, Pruijn GJ. All you wanted to know about anti-CCP but were afraid to ask. Autoimmun Rev. 2010;10(2):90–3. https://doi.org/10.1016/j.autrev.2010.08.009.CrossRefPubMed

11.

Sellam J, Hendel-Chavez H, Rouanet S, et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63(4):933–8. https://doi.org/10.1002/art.30233.CrossRefPubMed

12.

Visser K, Verpoort KN, van Dongen H, et al. Pretreatment serum levels of anti-cyclic citrullinated peptide antibodies are associated with the response to methotrexate in recent-onset arthritis. Ann Rheum Dis. 2008;67(8):1194–5. https://doi.org/10.1136/ard.2008.088070.CrossRefPubMed

13.

Rigby W, Buckner JH, Louis Bridges S Jr, et al. HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA. Arthritis Res Ther. 2021;23(1):245. https://doi.org/10.1186/s13075-021-02607-7.CrossRefPubMedPubMedCentral

14.

Huizinga TW, 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. 2015 ACR/ARHP Annual Meeting 2015.

15.

Sokolove J, Schiff M, Fleischmann R, et al. 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. Ann Rheum Dis. 2016;75(4):709–14. https://doi.org/10.1136/annrheumdis-2015-207942.CrossRefPubMed

16.

Harrold LR, Litman HJ, Connolly SE, et al. Effect of anticitrullinated protein antibody status on response to abatacept or antitumor necrosis factor-alpha therapy in patients with rheumatoid arthritis: a US national observational study. J Rheumatol. 2018;45(1):32–9. https://doi.org/10.3899/jrheum.170007.CrossRefPubMed

17.

Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis. 2009;68(12):1870–7. https://doi.org/10.1136/ard.2008.101121.CrossRefPubMed

18.

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(1):28–38. https://doi.org/10.1002/art.37711.CrossRefPubMedPubMedCentral

19.

Emery P, Burmester GR, Bykerk VP, et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015;74(1):19–26. https://doi.org/10.1136/annrheumdis-2014-206106.CrossRefPubMed

20.

Bristol-Myers Squibb Company. Highlights of Prescribing Information ORENCIA (abatacept) 2021. https://packageinserts.bms.com/pi/pi_orencia.pdf. Accessed 13 Mar 2023.

21.

Alemao E, Postema R, Elbez Y, et al. Presence of anti-cyclic citrullinated peptide antibodies is associated with better treatment response to abatacept but not to TNF inhibitors in patients with rheumatoid arthritis: a meta-analysis. Clin Exp Rheumatol. 2020;38(3):455–66.PubMed

22.

Courvoisier DS, Chatzidionysiou K, Mongin D, et al. The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries. Rheumatology (Oxford). 2021;60(2):820–8. https://doi.org/10.1093/rheumatology/keaa393.CrossRefPubMed

23.

Sung W, Tsai W. Rethink about the role of rheumatoid factor and anti-citrullinated protein antibody in rheumatoid arthritis. Rheumatol Immunol Res. 2021;2(1):19–25.CrossRefPubMedPubMedCentral

24.

Jabado O, Maldonado MA, Schiff M, et al. Differential changes in ACPA fine specificity and gene expression in a randomized trial of abatacept and adalimumab in rheumatoid arthritis. Rheumatol Therapy. 2022;9(2):391–409.CrossRef

25.

Wunderlich C, Oliviera I, Figueiredo CP, et al editors. Effects of DMARDs on citrullinated peptide autoantibody levels in RA patients—a longitudinal analysis. Seminars in arthritis and rheumatism. Amsterdam: Elsevier; 2017.

26.

Miriovsky BJ, Michaud K, Thiele GM, et al. Anti-CCP antibody and rheumatoid factor concentrations predict greater disease activity in men with rheumatoid arthritis. Ann Rheum Dis. 2010;69(7):1292–7.CrossRefPubMed

Title: Benefits of Autoantibody Enrichment in Early Rheumatoid Arthritis: Analysis of Efficacy Outcomes in Four Pooled Abatacept Trials
Authors: Kaleb Michaud
Philip G. Conaghan
Sang Hee Park
Karissa Lozenski
Mirko Fillbrunn
Vadim Khaychuk
Elyse Swallow
John Vaile
Henry Lane
Ha Nguyen
Janet Pope
Publication date: 25-05-2023
Publisher: Springer Healthcare
Keywords: Abatacept
Rheumatoid Arthritis
Published in: Rheumatology and Therapy / Issue 4/2023
Print ISSN: 2198-6576
Electronic ISSN: 2198-6584
DOI: https://doi.org/10.1007/s40744-023-00552-2

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2023

The Recent Outbreak of COVID-19 in China During the Omicron Variant Predominance: Clinical Features and Outcomes in Patients with Autoimmune Inflammatory Rheumatic Diseases

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry

Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry

Pain and Inflammation as Mediators of Tofacitinib Treatment Effect on Fatigue in Patients with Ankylosing Spondylitis: A Mediation Analysis

Patient–Physician Communication and Perception of Treatment Goals in Rheumatoid Arthritis: An Online Survey of Patients and Physicians

Mortality Trends Among Patients with Rheumatoid Arthritis in Western Australia

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials