Background Abatacept is a fully human fusion protein which selectively inhibits T-cell activation via the CD80/CD86:CD28 co-stimulation pathway and decreases serum levels of inflammatory cytokines and proteins implicated in the pathogenesis of psoriatic arthritis (PsA). Improvement in skin psoriasis with greatest reduction in PASI using 3 mg/kg dose of abatacept and reduction of clinical symptoms of PsA on 10 mg/kg dose has been previously shown. Data is limited on the immunopathological effect of abatacept in PsA synovial tissue.
Objectives (1) to study the change in immunohistochemical markers of synovial inflammation from baseline to 6 months after introducing abatacept treatment in patients with active PsA; (2) to evaluate the impact of a short period of abatacept 3 mg/kg treatment on both skin and joint-related clinical outcomes compared to placebo (PBO); (3) to investigate if cell markers of synovial inflammation correlate to disease activity measures and MRI synovitis scores.
Methods Biological treatment-naïve PsA patients with active disease for ≥3 months with clinical synovitis of a knee and the presence of a psoriatic skin lesion were enrolled. Patients were randomised to receive abatacept 3mg/kg or PBO infusion on day 1, 15 and 29; thereafter abatacept 10mg/kg was administered every 28 days for 5 months. Clinical data were collected at each visit.
Ga-enhanced MRI and arthroscopic synovial biopsy of the involved knee were obtained at 0, 2 and 6 months. Immunohistological staining for CD3, CD4, CD8, FoxP3 and CD31 was performed and expression was scored on a 5 point scale using a semi-quantitative method . FoxP3 (%/300 cells) and CD31 expression (number of positive vessels/10 HPF) was evaluated. The PsAMRIS semi-quantitative method was used to score MRI scans by one consultant radiologist. A total synovitis score (MRS (0-12)) per knee was calculated .
Results 15 patients (8 female/7 male) with mean age of 45 (±14.6) years were recruited. 4 were on methotrexate, the remainder had not received any prior DMARDs. 73% and 80% of patients were EULAR responders at 2 and 6 months. Non responders had significantly higher CRP at basleline; ESR, CRP, DAS28 ESR and DAS28 CRP at 2 months and higher enthesitis scores at 6 months compared to responders.
Preliminary synovial tissue analysis of the first 10 patients who completed the study revealed a reduction in expression for all cell markers as early as 2 months following treatment. There was a significant reduction in synovial CD4 expression at 6 months (p=0.038). Disease activity measures and cell markers did not show a significant difference between the treatment and PBO groups. MRS at baseline was lower (p=0.02) and change in DAS28 ESR 0 to 6 months was greater in the PBO group (p=0.08). Baseline DAS28 ESR significantly correlated with CD3, CD4 and FoxP3 expression at 6 months (rho=0.89 p=0.04).
Conclusions Abatacept reduced synovial CD4 positive T-cell expression in psoriatic arthritis over 6 months. DAS28 ESR at baseline correlated with all observed T-cell markers in the synovium 6 months following treatment.
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Rhodes LA et al. Rheumatology 2005;44:1569-73
Disclosure of Interest A. Szentpetery: None declared, J. McCormack: None declared, L. Mellerick: None declared, E. Heffernan: None declared, A. Fabre: None declared, O. FitzGerald Grant/research support from: Pfizer, AbbVie, BMS, MSD, Roche, UCB, Consultant for: Pfizer, AbbVie, BMS, MSD, Janssen, Roche, Speakers bureau: Pfizer, AbbVie, Janssen, Roche, UCB
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