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Increasing the threshold for patient global assessment in defining remission may have a different impact in patients with early and established rheumatoid arthritis
  1. Serena Bugatti1,2,
  2. Ludovico De Stefano1,2,
  3. Ennio Giulio Favalli3,
  4. Roberto Caporali3,4,
  5. Carlomaurizio Montecucco1,2
  1. 1Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Lombardia, Italy
  2. 2Division of Rheumatology, IRCCS S Matteo, Pavia, Lombardia, Italy
  3. 3Department of Rheumatology, Gaetano Pini-CTO, Milano, Lombardia, Italy
  4. 4Department of Clinical Sciences and Community Health, University of Milan, Milano, Lombardia, Italy
  1. Correspondence to Professor Serena Bugatti, Division of Rheumatology, University of Pavia, Pavia 27100, Italy;{at}

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A significant proportion of patients with rheumatoid arthritis (RA) misses the target of disease remission solely because of the patient global assessment of disease activity (PGA) exceeding the cut-off of 1.1–5 As PGA may also reflect non-inflammatory symptoms, its inclusion as a driver of intensification of immunosuppressive therapy is currently been questioned.6 Complete omission of the patients’ perspective, however, impairs functional outcomes and the ability to discriminate effective treatments from placebo.7 As such, different thresholds for the PGA are being tested, with a recent proposal from randomised clinical trials suggesting a suitable cut-off of 2.8

Here, we evaluated the performance of modifying the Boolean definition of remission9 by increasing the cut-off of the PGA to 28 in real life. Data were retrieved from 826 consecutive patients from two University Hospitals with an observation period of 12 months. Five hundred and thirty-five were patients with early RA (median (IQR) symptoms’ duration 16 [9–28] weeks) started on methotrexate aimed at low disease activity.10 Two hundred and ninety-one were established patients with RA (median (IQR) duration 6.7 [3.4–13.6] years) started on a biological drug (a tumour necrosis factor antagonist in 79.4% of the cases). In early RA, the rates of remission following PGA modification only slightly increased of +4.1% at 6 months and +4.3% at 12 months. Within remitters according to the Simplified Disease Activity Index (SDAI), simultaneous Boolean remitters increased from 65.7% at 6 months and 64.7% at 12 months with the original definition to 81.8% and 85.7% with the modified definition. However, modified Boolean remitters (original Boolean remitters excluded) were in SDAI remission in fewer cases compared with original Boolean remitters (40.9% vs 97.1% and 57.1% vs 96.7% at 6 and 12 months). As such, the concordance with SDAI remission was lower for modified compared with original Boolean remission at both time points (κ statistics 0.35, 95% CI 0.11 to 0.58 vs 0.74, 95% CI 0.67 to 0.82 and 0.52, 95% CI 0.28 to 0.75 vs 0.71, 95% CI 0.64 to 0.78). In contrast, in established RA, the increase in the remission rate was more pronounced (+7.3% and +12.5% at 6 and 12 months), and concordance with SDAI remission was higher compared with early RA (κ statistics 0.63, 95% CI 0.42 to 0.84 and 0.65, 95% CI 0.46 to 0.84 at the two time points). Patients in modified Boolean remission also showed different disease activity characteristics and functional outcomes in relation to disease duration (table 1). Indeed, in early RA, modified Boolean remitters at 6 months had significantly higher levels of C reactive protein (CRP) compared with original Boolean remitters. Furthermore, their Health Assessment Questionnaire (HAQ) at 12 months worsened of a clinically significant mean (SD) of 0.24 (0.31) points compared with functional stability in original Boolean remitters, and an HAQ ≤0.5 was observed in fewer cases. In contrast, in established RA, CRP levels, HAQ variations and the rate of good functional outcome (HAQ ≤0.5) at 12 months were comparable between modified and original Boolean remitters.

Table 1

Comparison of disease characteristics and functional outcomes according to the original and the modified definition of remission

The inclusion of patients from a real-life clinical setting, with different disease duration, activity and treatment protocols hampers any comparison with published studies,8 and our observations need confirmation in independent cohorts. However, our data suggest that a cut-off of the PGA of 2 increases the rates of remission without impacting on outcomes in patients with established RA. In contrast, in early disease, before changes in pain processing mechanisms have occurred,11 the PGA may more strictly collect information on inflammatory-related symptoms, and even small increases of its cut-off may affect functional outcomes. Better understanding of the relationship between patient-reported outcomes and disease activity in the various phases of RA may thus be needed before introducing definitive changes in the current definition of remission.


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  • Contributors SB contributed to the conception of the work, to the analysis and interpretation of data and to the drafting of the work. LDS contributed to the acquisition and analysis of data and to the drafting of the work. EGF contributed to the acquisition and interpretation of data and revised the manuscript critically. RC revised the manuscript critically for important intellectual content. CM contributed to the conception of the work and revised the manuscript critically for important intellectual content. All the authors provided final approval of the version to be published.

  • Funding This study was supported in part by fundings from the IRCCS Policlinico San Matteo Foundation, Pavia, Italy.

  • Competing interests None declared.

  • 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 IRCCS Policlinico San Matteo Foundation Ethics Committee n.20070001302. ASST Gaetano Pini-CTO Institute Ethics Committee

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

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