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Original article
ACPA and RF as predictors of sustained clinical remission in patients with rheumatoid arthritis: data from the Ontario Best practices Research Initiative (OBRI)
  1. Janet E Pope1,
  2. Mohammad Movahedi2,3,
  3. Emmanouil Rampakakis2,
  4. Angela Cesta3,
  5. John S Sampalis2,4,
  6. Edward Keystone5,
  7. Carter Thorne6 and
  8. Claire Bombardier3,5,7
  9. Ontario Best Practices Research Initiative investigators
    1. 1Department of Medicine, Division of Rheumatology, University of Western Ontario, Saint Joseph’s Health Care, Ontario, London, Canada
    2. 2JSS Medical Research, St-Laurent, Quebec, Canada
    3. 3Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
    4. 4McGill University, Montreal, Quebec, Canada
    5. 5Department of Medicine, Division of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada
    6. 6Southlake Regional Health Centre, Newmarket, Ontario, Canada
    7. 7Department of Medicine and Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
    1. Correspondence to Dr Janet E Pope; janet.pope{at}sjhc.london.on.ca

    Abstract

    Objective(s) This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice.

    Methods Patients with RA enrolled in the Ontario Best Practices Research Initiative registry, with ≥1 swollen joint, autoantibody information and ≥1 follow-up assessment were included. Sustained clinical remission was defined as Clinical Disease Activity Index (CDAI) ≤2.8 in at least two sequential visits separated by 3–12 months. Time to sustained remission was assessed using cumulative incidence curves and multivariate cox regression.

    Results Among 3251 patients in the registry, 970 were included, of whom 262 (27%) were ACPAneg/RFneg, 60 (6.2%) ACPApos /RFneg, 117 (12.1%) ACPAneg/RFpos and 531 (54.7%) ACPApos /RFpos at baseline. Significant between group differences were observed in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02) and Health Assessment Questionnaire (p=0.002), with ACPApos patients being youngest with lowest disease activity and disability. No difference in biologic use was found between groups (20.2% of patients).

    Over a mean follow-up of 3 years, sustained remission was achieved by 43.5% of ACPApos/RFpos patients, 43.3% of ACPApos /RFneg patients, 31.6 % of ACPAneg/RFpos patients and 32.4% of ACPAneg/RFneg patients (p=0.01). Significant differences were observed in CDAI improvement based on ACPA and RF status where ACPApos/RFpos had a shorter time to achieving sustained remission (HR 1.30; 95% CI 1.01 to 1.67) and experienced significantly higher improvements compared with ACPAneg/RFneg patients.

    Conclusion(s) Combined ACPA and RF positivity were associated with improved and faster response to antirheumatic medications in patients with RA.

    • rheumatoid arthritis
    • early rheumatoid arthritis
    • anti-citrullinated protein antibody
    • rheumatoid factor
    • disease activity

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • Collaborators The authors wish to acknowledge OBRI-RA investigators: Ahluwalia V, Ahmad Z, Akhavan P, Albert L, Alderdice C, Aubrey M, Bajaj S, Bensen B, Bhavsar S, Bobba R, Bombardier C, Bookman A, CaretteS, Carmona R, Chow A, Ciaschini P, Cividino A, Cohen D, Dixit S, Haaland D, Hanna B, Haroon N, Hochman J, Jaroszynska A,Johnson S, Joshi R, Kagal A, Karasik A, Karsh J, Keystone E, Khalidi N, Kuriya B, Larche M, Lau A, LeRiche N, Leung Fe, Leung Fr, Mahendira D, Matsos M, McDonald-Blumer H, Mittoo S,Mody A, Montgomery A, Mulgund M, Ng E, Papneja T, Pavlova P, Perlin L, Pope J, Purvis J, Rohekar G, Rohekar S, Ruban T, Samadi N, Shaikh S, Shickh A, Shupak R, Smith D, Soucy E, Stein J, Thompson A, Thorne C, Wilkinson S.

    • Contributors All authors contributed in the conception or design of the work, revised the work critically and approved the final version of the manuscript. MM and ER conducted the data analysis and drafted the manuscript.

    • Funding No funding has been provided for this manuscript. OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB.

    • Competing interests No funding has been provided for this manuscript. JP has done research studies and/or consulting for AbbVie, Amgen, BMS, GSK, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB. ER and JSS: none relevant to this project; employees at JSS Medical Research, a Contract Research Organization. EK has received sources of funding for research from Abbott Laboratories, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche, Gilead, Janssen, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis; has a consulting agreement and is a member of an advisory board for Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche, Genentech, Gilead, Janssen, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB, Sandoz and received speaker honoraria agreements for Amgen, Abbott Laboratories, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche, Janssen, Merck, Pfizer Pharmaceuticals, Sanofi Genzyme UCB. CT has served in advisory boards for AbbVie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer and Sanofi; has been a consultant for AbbVie, Centocor, Janssen, Lilly, Medexus/Medac and Pfizer; has been a speaker for Medexus/Medac; has participated in investigator-initiator studies supported by Amgen and Pfizer and has participated in randomised controlled trials supported by AbbVie, Celgene, CaREBiodam, Novartis and Pfizer. MM, AC, and CB are employees at OBRI. OBRI was funded by peer reviewed grants from Canadian Institute for Health Research (CIHR), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB.

    • Patient consent Obtained.

    • Ethics approval All sites had ethics approval to enrol patients. All patients signed informed consent. Ethics approval: REB# is 07-0729 AE (University of Toronto).

    • Provenance and peer review Not commissioned; externally peer reviewed.

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