An immunological biomarker to predict MTX response in early RA. Issue 11 (29th August 2013)

• Record Type: Journal Article
• Authors: Ponchel, Frederique; Goëb, Vincent; Parmar, Rekha; El-Sherbiny, Yasser; Boissinot, Marjorie; El Jawhari, Jehan; Burska, Agata; Vital, Edward M; Harrison, Stephanie; Conaghan, Philip G; Hensor, Elizabeth; Emery, Paul
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Issue 11(2014)
• Page Start: 2047
• Page End: 2053
• Publication Date: 2013-08-29
• Subjects: Naïve T-cell -- regulatory T-cells Rheumatoid arthritis -- remission; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-203566
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis and appropriate therapeutic intervention. RA is associated with dysregulation of T-cell subsets (naïve, regulatory (Treg) and inflammation-related cells (IRC)) early in the disease. Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission with early treatment in RA. Methods: T-cell subsets were quantified in 108 drug-naïve, early RA patients commencing methotrexate (MTX) or MTX+antitumor necrosis factor (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28<2.6). A pilot study used frozen cells (38 patients and 35 HCs, see online supplementary material ) and was validated with fresh blood (70 patients and 70 HCs). Results: Immune dysregulation in early RA was confirmed with an association between age and reduced naïve cells compared with HCs (p=0.006), a lower age-adjusted Treg and higher IRC frequency (p=0.001). Anticitrullinated peptide antibody (ACPA) positivity was associated with lower naïve (p=0.031) and Treg frequencies (p=0.039). In 50 patients treated with MTX, ACPA/age-adjusted analysis demonstrated that higher naïve cell frequency (relative to HC) was associated with remission (OR 5.90 (1.66 to 20.98), p=0.006, sensitivity/specificity 62%/79%, Positive Predictive Value (PPV)/Negative Predictive Value (NPV) 66%/76%). Remission with MTX+anti-TNF (n=20) was not found to be associated with naïve cell frequency, and for patients with reduced naïve cells the remission rate increased from 24% (MTX) to 42% (MTX+anti-TNF). Conclusions: Baseline T-cell subset analysis has a value in predicting early RA remission with first therapy with MTX. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and help select the most appropriate therapy at disease presentation.