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Revisiting the use of remission criteria for rheumatoid arthritis by excluding patient global assessment: an individual meta-analysis of 5792 patients
  1. Ricardo J O Ferreira1,2,
  2. Paco M J Welsing3,
  3. Johannes W G Jacobs3,
  4. Laure Gossec4,5,
  5. Mwidimi Ndosi6,
  6. Pedro M Machado7,8,9,
  7. Désirée van der Heijde10,
  8. Jose A P Da Silva1,11
  1. 1 Rheumatology, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal
  2. 2 Health Sciences Research Unit: Nursing (UICISA: E), Escola Superior de Enfermagem de Coimbra, Coimbra, Portugal
  3. 3 Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
  4. 4 Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France
  5. 5 Rheumatology, Pitié Salpêtrière Hospital, AP-HP, Paris, France
  6. 6 Faculty of Health and Applied Sciences, University of the West of England Bristol, Bristol, UK
  7. 7 Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, UK
  8. 8 Rheumatology, University College London Hospitals NHS Foundation Trust, London, UK
  9. 9 Rheumatology, Northwick Park Hospital, London North west UniversityHealthcare NHS Trust, London, UK
  10. 10 Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  11. 11 Clínica Universitária de Reumatologia, and i-CBR Coimbra Institute for Clinical and Biological Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  1. Correspondence to Professor Jose A P Da Silva, Rheumatology, Centro Hospitalar e Universitario de Coimbra EPE, 3000-076 Coimbra, Portugal; jdasilva{at}


Objectives To determine the impact of excluding patient global assessment (PGA) from the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission criteria, on prediction of radiographic and functional outcome of rheumatoid arthritis (RA).

Methods Meta-analyses using individual patient data from randomised controlled trials testing the efficacy of biological agents on radiographic and functional outcomes at ≥2 years. Remission states were defined by 4 variants of the ACR/EULAR Boolean definition: (i) tender and swollen 28-joint counts (TJC28/SJC28), C reactive protein (CRP, mg/dL) and PGA (0–10=worst) all ≤1 (4V-remission); (ii) the same, except PGA >1 (4V-near-remission); (iii) 3V-remission (i and ii combined; similar to 4V, but without PGA); (iv) non-remission (TJC28 >1 and/or SJC28 >1 and/or CRP >1). The most stringent class achieved at 6 or 12 months was considered. Good radiographic (GRO) and functional outcome (GFO) were defined as no worsening (ie, change in modified total Sharp score (ΔmTSS) ≤0.5 units and ≤0.0 Health Assessment Questionnaire–Disability Index points, respectively, during the second year). The pooled probabilities of GRO and GFO for the different definitions of remission were estimated and compared.

Results Individual patient data (n=5792) from 11 trials were analysed. 4V-remission was achieved by 23% of patients and 4V-near-remission by 19%. The probability of GRO in the 4V-near-remission group was numerically, but non-significantly, lower than that in the 4V-remission (78 vs 81%) and significantly higher than that for non-remission (72%; difference=6%, 95% CI 2% to 10%). Applying 3V-remission could have prevented therapy escalation in 19% of all participants, at the cost of an additional 6.1%, 4.0% and 0.7% of patients having ΔmTSS >0.0, >0.5 and >5 units over 2 years, respectively. The probability of GFO (assessed in 8 trials) in 4V-near-remission (67%, 95% CI 63% to 71%) was significantly lower than in 4V-remission (78%, 74% to 81%) and similar to non-remission (69%, 66% to 72%).

Conclusion 4V-near-remission and 3V-remission have similar validity as the original 4V-remission definition in predicting GRO, despite expected worse prediction of GFO, while potentially reducing the risk of overtreatment. This supports further exploration of 3V-remission as the target for immunosuppressive therapy complemented by patient-oriented targets.

  • rheumatoid arthritis
  • patient perspective
  • outcomes research
  • inflammation
  • disease activity

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  • RJOF and PMJW are joint first authors.

  • Handling editor Josef S Smolen

  • Twitter @FerreiraRJO, @ndosi, @pedrommcmachado

  • Contributors All authors designed the study and protocol, which was firstly drafted by RJOF and JAPS. RJOF and PMJW performed the data analyses. RJOF and JAPS wrote the initial draft of the manuscript, which was critically revised and refined by all authors. All authors formally approved the final manuscript.

  • Funding This manuscript is based on research using data from data contributors AbbVie, Pfizer and UCB that have been made available through Vivli, Inc. This study was also supported by CSDR (ClinicalStudyDataRequest), which has an agreement with Roche Inc. (Project no. 1808). Data were also obtained from the Yale University Open Data Access Project (YODA Project no. 2017-1451), which has an agreement with Janssen Research & Development, LLC. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). RJOF was supported by a grant from ARCo – Associação de Reumatologia de Coimbra, a non-profit association of health professionals.

  • Competing interests RJOF reports a research grant from Abvvie and speaker fees from Sanofi Genzyme, Amgen, MSD and UCB Pharma. JWGJ reports a research grant from Roche. LG reports a research grant from Lilly, Mylan, Pfizer and Sandoz, and speaker fees from AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi-Aventis and UCB Pharma. MN reports a research grant from Bristol Myers Squibb, and speaker fees from Janssen and Pfizer. PMM reports speaker fees from Abbvie, Celgene, Janssen, Lilly, MSD, BMS, Novartis, Pfizer, Roche and UCB Pharma. DvdH is Director of Imaging Rheumatology bv and reports speaker fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma. JAPS reports a research grant from Pfizer and Abvvie, and speaker fees from Pfizer, AbbVie, Roche, Lilly and Novartis.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval to this study was granted by the Centro Hospitalar e Universitário de Coimbra Ethics Committee (CHUC-047–17).

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

  • Data availability statement Data may be obtained from a third party and are not publicly available.

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