Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint

Abstract

IntroductionThe purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA).MethodsSystemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105.ResultsAt baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3).ConclusionsSynovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.

Progress in intra-articular therapy

“…Although no randomized controlled trial has been performed, anecdotal reports indicate outcomes of success in treating spondyloarthritis, RA and OA. 33–35 However, intra-articular delivery of proteinaceous anti-TNF agents has not become a mainstay of clinical care.…”

Role of scintigraphy with 99mTc-infliximab in predicting the response of intraarticular infliximab treatment in patients with refractory monoarthritis

“…In the last few years, some experience with intraarticular (IA) treatment with TNF antagonists in patients with refractory monoarthritis has been reported. The majority of these patients have been treated with infliximab, and only a few studies have evaluated the efficacy of etanercept and adalimumab IA treatment [4][5][6][7][8][9][10][11][12][13][14][15].…”

Biomarkers in psoriasis and psoriatic arthritis

“…A change in CD68 cell infiltration as observed in RA was not confirmed, supporting the idea that RA and PsA are distinct diseases 59. Pro-inflammatory cytokines and promoters of angiogenesis are upregulated in PsA synovial fluid, with cytokines such as IL-1, IL-1-RA, IL-6, IL-8 and CCL3 correlating with systemic markers of inflammation (erythrocyte sedimentation rate and CRP) and decreasing following intra-articular therapy with anti-TNF 60. In PsA, clonally expanded CD8 T cells are found independently from CD4 T cells,7 and activated T cells in synovial fluid in PsA also contribute to osteoclastogenesisis and following bone resorption 61…”