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  1. C. Duarte1,
  2. R. J. O. Ferreira2,
  3. P. Welsing3,
  4. J. W. G. Jacobs3,
  5. L. Gossec4,
  6. P. Machado5,
  7. D. Van der Heijde6,
  8. J. A. P. Da Silva1
  1. 1Centro Hospitalar e Universitário de Coimbra, Rheumatology, Coimbra, Portugal
  2. 2Nursing School of Lisbon (ESEL), Nursing Research, Innovation and Development Centre of Lisbon (CIDNUR), Lisboa, Portugal
  3. 3UMC Utrecht, Rheumatology & Clinical Immunology, Utrecht, Netherlands
  4. 4Sorbonne Université, and Pitié Salpêtrière Hôpital, Rheumatology, Paris, France
  5. 5University College London, Centre for Rheumatology & Department of Neuromuscular Diseases, London, United Kingdom
  6. 6LUMC, Rheumatology, Leiden, Netherlands


Background Remission is the target for the management of rheumatoid arthritis (RA). However, the best definition of remission is still under debate, particularly regarding the inclusion of patient global assessment (PGA).[1] An increased cut-off for PGA (from ≤1 to ≤2cm) was recently proposed by ACR/EULAR for its Boolean-based criteria,[2] but others have suggested to replace PGA by the Physician’s Global Assessment (PhGA)[3], or to simply drop PGA (ie, 3-Variable Boolean remission) when the objective is to guide immunosuppressive therapy.[2] Radiographic progression is a relevant reference standard to investigate as outcome of persistent/residual disease activity.

Objectives To assess which definition of remission best predicts good radiographic outcome (GRO) in RA.

Methods Meta-analyses using individual patient data (IPD) from 8 randomized controlled trials assessing the efficacy of bDMARDs on radiographic outcomes in RA. Six different definitions of remission were considered: i) The ACR/EULAR Boolean with 4 variables (Boolean 4v) with PGA≤1 (4vPGA); ii) SDAI≤3.3; iii) CDAI≤2.8; iv) Boolean 4v with PGA≤2 (4vPGA2); v) Boolean 4v replacing PGA by PhGA (4vPhGA), and vi) Boolean excluding PGA (3v). Good radiographic outcome (GRO) was defined as an increase of ≤0.5 modified Total Sharp score (mTSS) units. The relationship between achieving each remission definition at 6 and/or 12 months and GRO during the second year was analysed. The pooled probabilities of GRO for the different definitions of remission were estimated and compared, as well as their predictive accuracy (True Positive + True Negative). Meta-analyses were performed using the DerSimonian-Laird random-effects method.

Results IPD from 4423 patients of 8 RCTs were analysed. 4vPGA remission was achieved by 24.3% of patients and 3V remission by 43.4%. The adoption of the recently proposed PGA≤2 cut-off results in an “in-between” rate of 32.4% (Table 1). GRO was observed in 77.6% of all patients, ranging from 65 to 91% in different trials. GRO among patients achieving remission ranged from 82.4% (3v) to 83.9% (SDAI), without any statistically significant difference between the 6 definitions considered. Boolean 3v remission showed a higher predictive accuracy (51.1%, 95%CI: 46.9-55.6%) than 4vPGA (38.8%, 95%CI: 34.1-43.5%). The 4vPhGA and the 4vPGA2 remission definitions performed in between, providing a correct prediction in 43.8 and 44.8% of the cases, respectively. The performance of SDAI- and CDAI-based definitions were, overall, very similar to that of 4vPGA. (Figure 1)

Table 1.

Rates of remission and good radiographic outcomes in the included studies

Conclusion The Boolean 3v remission provided the most accurate prediction of GRO, even better than 4vPGA2 and 4vPhGA remission. The use of the 3v definition in treatment recommendations would avoid the risk of overtreatment in a significant proportion of patients, with a minor increment in radiographic damage progression, validating 3v-remission as a preferable guide for immunosuppressive treatment. The patient’s perspective, which must remain central, is best served by a dedicated autonomous target, rather than PGA: a dual-target approach.

References [1] Studenic P, et al. Ann Rheum Dis. 2022. doi: 10.1136/ard-2022-223413

[2] Ferreira R, et al. Ann Rheum Dis. 2022. doi: 10.1136/annrheumdis-2021-221917

[3] Pazmino S, et al. J Rheumatol. 2021;48(2):174-8

Acknowledgements This study was based on research using data from data contributors AbbVie, Pfizer, UCB and Roche that have been made available through Vivli.Inc. These companies provided the authors with access to the data but did not sponsor this effort. The interpretation and reporting of the results are solely the responsibility of the authors. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.

Disclosure of Interests None Declared.

  • Remission
  • Treat to target
  • Rheumatoid arthritis

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