Successful adalimumab (Humira) therapy in patients with psoriatic arthritis is associated with reductions in T-cell infiltration and matrix metalloproteinase (MMP)-13 expression in synovial tissue, say Dutch researchers in findings that may help in assessing responses to novel drugs.
Paul Tak, from the University of Amsterdam, and colleagues randomly assigned 24 patients with active psoriatic arthritis, who had not used any other disease-modifying anti-rheumatic drug for a month prior to baseline, to receive adalimumab 40 mg or placebo at day 1 and 15.
Immunohistochemical analysis of synovial biopsies obtained at baseline and after 28 days from 19 patients was used to characterize cell infiltrate, the expression of cytokines and MMPs, and vascularity.
The average age of adalimumab patients was 42.8 years, compared with 47.2 years for placebo patients. The team found that the disease activity score in 28 joints (DAS28) decreased in adulimumab patients but remained stable in those given placebo, giving a significant difference of 1.92 after 4 weeks.
Eleven adalimumab patients fulfilled the European League Against Rheumatism criteria for a clinical response after 4 weeks and all 12 patients met the criteria by week 12, compared with none of those given placebo.
Analysis of synovial samples revealed a significant improvement in CD3+ cell count with adalimumab therapy, with a median reduction of 212 versus a 36-cells/mm2 increase with placebo.
The expression of MMP-13 was also reduced significantly with adalimumab therapy, to 18,190 integrated optical density/mm2 lower than placebo.
"This study clearly shows that changes in T-cell numbers and the expression of MMP-13 in the synovium of psoriatic arthritis patients may be used as biomarkers to screen for effective therapies during early drug development," the team writes in the Annals of the Rheumatic Diseases.