Abstract
BackgroundThe aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA).MethodsBiological-treatment-naïve PsA patients with active disease including synovitis of a knee were enrolled in this single-centre, crossover study. Patients were randomised to receive intravenous abatacept 3 mg/kg of body weight or placebo infusion on day 1, 15 and 29; thereafter abatacept 10 mg/kg of body weight was administered every 28 days for 5 months. Clinical data were collected at each visit. Synovial biopsy of the involved knee was obtained at baseline and 2 and 6 months. MRI of the same knee and skin biopsy was performed prior to arthroscopy.ResultsFifteen patients were recruited. Significant improvements in the joint-related measures were observed; 90% were European League Against Rheumatism criteria responders and 30% achieved psoriasis area severity index (PASI)50 at 6 months. Reduction in synovitis (P = 0.016) and vascularity (P = 0.039) macroscopic scores consistent with decrease in total MRI score (P = 0.016) were noticed. Abatacept decreased the immunohistological expression of FOXP3+ cells (P = 0.027), specifically the expression of CD4+FOXP3+ regulatory T cells (Tregs) (P = 0.008) in the synovium over 6 months. There was no significant clinical or immunohistological change in any of the skin measures.ConclusionThis is the first study assessing synovial and psoriatic skin immunpathological changes following abatacept treatment in PsA. Reduction in Treg expression in the synovium but not in the psoriatic lesion suggests abnormal Treg function in PsA with differential suppressive capacity in the synovium compared to the lesional skin. The results of this study demonstrate that abatacept 10 mg/kg of body weight might be an effective treatment option for joint disease in patients with PsA.Trial registrationIrish Health Products Regulatory Authority. Trial registration number: CT 900/489/1 – Abatacept (case number: 2077284, EudraCT Number: 2009-017525-19, Protocol number: 77777). Registered on 12 March 2010.
Highlights
The aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA)
Four patients were on a stable dose of MTX at the time of recruitment and stayed on the same dose of MTX, the remainder had not received any prior Disease-modifying antirheumatic drugs (DMARDs); one patient (PBO arm) was on a stable dose of prednisolone 5 mg/day
We found significant reduction in macroscopic scores for both synovitis and vascularity after 6 months of abatacept therapy
Summary
The aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA). Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease that affects peripheral joints, entheses and axial sites along with skin and nails. Regulatory T cells (Tregs) are a subset of CD4+ CD25high T lymphocytes that require forkhead box transcription factor (FOXP3) for their suppressive function [4, 8, 9]. Increased Treg expression compared to normal skin has been reported in psoriatic lesions, irrespective of the disease severity. Previous studies indicated an abnormal phenotype and impaired function of synovial Tregs in rheumatoid arthritis (RA) and increased FOXP3 expression in synovial CD4+ T cells in rheumatoid factor (RF)-negative RA and PsA compared to seropositive RA [10,11,12]. Tregs isolated from peripheral blood and psoriatic skin have dysfunctional activity in suppressing effector T-cell responses in psoriasis [13,14,15,16]
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