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A3.3 An Immunological Window of Opportunity Defines the Ability of Early RA Patient to Achieve Remission with First Anti-Rheumatic Treatment
  1. Agata Burska,
  2. Rekha Parmar,
  3. Yasser El-Sherbiny,
  4. Jehan El Jawhari,
  5. Paul Emery,
  6. Frederique Ponchel
  1. University of Leeds, Leeds, UK

Abstract

Background and Objectives The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells and regulatory T-cell losses and acquisition of abnormal subset in realtion with inflammation (IRC). Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission in patients with early RA.

Materials and Methods T-cell subsets (naive, Treg and IRC) were quantified using flow cytometry in 108 DMARDs-naïve, early RA patients (<24 months) symptom duration commencing methot-rexate MTX or MTX + anti-tumour necrosis factor agents (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28 < 2.6). The pilot analysis was performed on frozen PBMC obtained from 38 RA patients and 35 HC. These results were validated using fresh blood samples on a cohort of 70 RA patients and 70 HC.

Results In the pilot study, T-cell subset analysis in early RA confirmed immune dysregulation compared to HC with reduced frequency of naïve CD4+ T-cells and Treg and increased IRC (all p < 0.001) compared to HC. Naive T-cell above median was associated with remission (p = 0.001). In the validation study, 50 patients were treated with MTX and showed the same relationship with naïve cell frequency above median being associated with remission (p = 0.011). Individual analysis on each patient’s naïve cell frequency deviation from expected (using 70 HC) demonstrated that “normal” naïve cell frequency (observed in 30 patients) was associated with remission whereas reduced naïve cell frequency was more frequently observed in patients with poor response to MTX (p = 0.03). Patients with poor immunological status were not prevented to achieve remission when treated with MTX + anti-TNF (n = 20 including 10 patients with normal and 10 with reduced naïve cells) raising the rate of remission from 20% in the MTX group (n = 4 of the 20 patients with reduced naïve cells at baseline) to 60% in the MTX + anti-TNF group (n = 6 of the 10 patients).

Conclusions These data show that baseline naïve T-cell subset analysis has a value in predicting early RA MTX treatment outcome. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and select the most appropriate therapy at disease presentation.

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