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Clinical Trial
. 2004 Jul;63(7):769-73.
doi: 10.1136/ard.2003.018085.

Early effects of tumour necrosis factor alpha blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis

Affiliations
Clinical Trial

Early effects of tumour necrosis factor alpha blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis

A Y Goedkoop et al. Ann Rheum Dis. 2004 Jul.

Abstract

Background: Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA).

Objective: To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples.

Methods: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis.

Results: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2)v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation.

Conclusions: The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.

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Figures

Figure 1
Figure 1
Representative images of CD3+ immunohistochemical staining and TUNEL assay in lesional psoriatic skin at baseline and 48 hours after initiation of infliximab treatment. Original magnification x400.
Figure 2
Figure 2
Representative images of CD3+ and CD68+ immunohistochemical staining and TUNEL assay in synovial tissue at baseline and 48 hours after initiation of infliximab treatment. Original magnification x400.

References

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