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SAT0053 The incident immunological status predicts drug-free disease flare in rheumatoid arthritis patients achieving stringent clinical and ultrasonographic control of the peripheral inflammatory process
  1. A Manzo,
  2. S Bugatti,
  3. F Benaglio,
  4. B Vitolo,
  5. G Sakellariou,
  6. R Caporali,
  7. C Montecucco
  1. Rheumatology and Translational Immunology Research Laboratories (LaRIT), Division of Rheumatology, IRCCS Policlinico San Matteo Foundation/University of Pavia, Pavia, Italy


Background The development of predictive tools to evaluate health risks and design personalized health plans in patients with rheumatoid arthritis (RA) achieving remission still represents a major unmet need. In this perspective, the relative weight of clinical, ultrasound and immunological assessment of disease characteristics for predicting recurrence of the inflammatory process under drug-free conditions remains unclear.

Objectives To investigate the predictive value of baseline clinical remission stringency, synovial power Doppler (PD) ultrasound indices and the incident autoimmune status, as predictors of flare under drug-free conditions after a DAS28-driven treatment strategy with methotrexate (MTX) in early RA.

Methods 85 RA patients achieving stable remission and candidate to MTX withdrawal were recruited according to the following criteria: 1) introduction of MTX within 12 months from symptoms' onset, 2) at least 24 months of MTX treatment with a DAS28-driven protocol targeting low disease activity (LDA), 3) DAS28<2.6 for ≥6 months in the absence of corticosteroids. Following treatment suspension, patients were monitored at three months' intervals across 24 months through clinical, ultrasound (hands-feet-axillary lymph nodes), radiographic and immunologic screenings (ACPA-RF status, CXCL13 circulating levels [1–2] and FACS analysis for quantification of Ki67+/regulatory T-B cell subsets). Treatment was re-introduced in case of DAS28≥3.2 or stable LDA.

Results At baseline, 84% of the patients were in remission according to the SDAI (<3,3) with 44% of the cases showing SDAI remission and absence of PD signal in hands and feet (SDAI<3,3 and PD=0). Despite stringent remission, 48% of the patients showed an episode of flare during follow-up with a peak incidence between 6 and 9 months after drug withdrawal. With the exception of a mild protective role of SDAI remission, none of the investigated clinical and ultrasound parameters (alone or in combination) showed a significant impact on clinical evolution across 24 months. ACPA IgG levels showed instead a strong, inflammation-independent predictive value for disease recurrence, an observation that was confirmed in the overall cohort (HR: 3.39 [1.7–6.64], p=0.0006, Cox regression) and, invariably, across progressive clinical and/or ultrasound remission thresholds (SDAI remission, SDAI remission-PD=0). Sub-analyses focused on short-term events (0–6 months after DMARDs withdrawal), identified the systemic level of CXCL13 at baseline as the strongest predictor of early disease recurrence in ACPA IgG positive individuals.

Conclusions The systemic immuno-type of patients in remission is the major determinant of drug-free disease recurrence, over and above drug-induced achievement of stringent clinical and ultrasonographic control of the peripheral inflammatory process.


  1. Meeuwisse CM et al. Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint. Arthritis Rheum 2011; 63: 1265–73.

  2. Havenar-Daughton C et al. CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci U S A 2016; 113: 2702–7.


Disclosure of Interest None declared

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