Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis - a prospective cohort study

Tomas Weitoft, Johan Rönnelid, Ann Knight, Jörgen Lysholm, Tore Saxne, Anders Larsson, Tomas Weitoft, Johan Rönnelid, Ann Knight, Jörgen Lysholm, Tore Saxne, Anders Larsson

Abstract

Introduction: Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA).

Methods: In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor).

Results: During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002).

Conclusions: Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.

Figures

Figure 1
Figure 1
Synovial fluid levels of VEGF among responders and non reponders. VEGF, vascular endothelial growth factor.

References

    1. Caldwell JR. Intra-articular corticosteroids. Guide to selection and indications for use. Drugs. 1996;52:507–514. doi: 10.2165/00003495-199652040-00004.
    1. Jones A, Regan M, Ledingham J, Pattrick M, Manhire A, Doherty M. Importance of placement of intra-articular steroid injections. BMJ. 1993;307:1329–1330. doi: 10.1136/bmj.307.6915.1329.
    1. Weitoft T, Uddenfeldt P. Importance of synovial fluid aspiration when injecting intra-articular corticosteroids. Ann Rheum Dis. 2000;59:233–235. doi: 10.1136/ard.59.3.233.
    1. Chakravarty K, Pharoah PD, Scott DGI. A randomized controlled study of post-injection rest following intra-articular steroid therapy for knee synovitis. Br J Rheumatol. 1994;33:464–468. doi: 10.1093/rheumatology/33.5.464.
    1. Green M, Marzo-Ortega H, Wakefield RJ, Astin P, Proudman S, Conaghan PG, Hordon L, Emery P, Hordon L, Emery P. Predictors of outcome in patients with oligoarthritis: results of a protocol of intraarticular corticosteroids to all clinically active joints. Arthritis Rheum. 2001;44:1177–1183. doi: 10.1002/1529-0131(200105)44:5<1177::AID-ANR201>;2-5.
    1. Luukkiainen R, Hakala M, Sajanti E, Huhtala H, Yli-Kerttula U, Hämenkorpi R. Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis. Ann Rheum Dis. 1992;51:874–876. doi: 10.1136/ard.51.7.874.
    1. Jahangier ZN, Jacobs JW, Kraan MC, Wenting MJ, Smeets TJ, Bijlsma JW, Lafeber FP, Tak PP. Pre-treatment macrophage infiltration of the synovium predicts the clinical effect of both radiation synovectomy and intra-articular glucocorticoids. Ann Rheum Dis. 2006;65:1286–1292. doi: 10.1136/ard.2005.042333.
    1. Lund Hetland M, Østergaard M, Ejbjerg B, Jacobsen S, Stengard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Svendsen A, Pedersen JK, Kjødt H, Ellingsen T, Lindegaard H, Pødenphant J, Hørslev Pedersen K. CIMESTRA study group. Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of MRI findings, anti-CCP, IgM-RF and CRP. Ann Rheum Dis. 2012;71:851–856. doi: 10.1136/annrheumdis-2011-200632.
    1. Arnett FC, Edworthy SM, Bloch DA, Shane DA, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–324. doi: 10.1002/art.1780310302.
    1. Steinbrocker O, Traeger CH, Betterman RC. Therapeutic criteria in rheumatoid arthritis. JAMA. 1949;140:659–662. doi: 10.1001/jama.1949.02900430001001.
    1. Ekdahl C, Eberhardt K, Andersson SI, Svensson B. Assessing disability in patients with rheumatoid arthritis. Scand J Rheumatol. 1988;17:263–271. doi: 10.3109/03009748809098795.
    1. Prevoo ML, Van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight joint counts. Development of and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–48. doi: 10.1002/art.1780380107.
    1. Larsen A, Dale K. In: The Recognition of Antirheumatic Drugs. Dumonde DC, Jasani MK, editor. Lancaster: MTP Press; 1978. Standardized radiological examination of rheumatoid arthritis in therapeutical trials; pp. 285–292.
    1. Saevarsdottir S, Wedren S, Seddighzadeh M, Bengtsson C, Wesley A, Lindblad S, Askling J, Alfredsson L, Klareskog L. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum. 2011;63:26–36. doi: 10.1002/art.27758.
    1. af Klint E, Gruntman C, Engström M, Catrina A, Makrygiannakis D, Klareskog L, Andersson U, Ulfgren AK. Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels. Arthritis Rheum. 2005;52:3880–3889. doi: 10.1002/art.21488.
    1. Yoo SA, Kwok SK, Kim WU. Proinflammatory role of vascular endothelial growth factor in the pathogenesis of rheumatoid arthritis: prospects for therapeutic intervention. Mediators Inflamm. 2008;2008:129873.
    1. Kim WU, Kang SS, Yoo SA, Hong KH, Bae DG, Lee MS, Hong SW, Chae CB, Cho CS. Interaction of vascular endothelial growth factor 165 with neurophilin-1 protects rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and Bax translocation. J Immunol. 2006;6:5727–5735.
    1. Mould AW, Tonks ID, Cahill MM, Pettit AR, Thomas R, Hayward NK, Kay GF. Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Arthritis Rheum. 2003;48:2660–2669. doi: 10.1002/art.11232.
    1. Sone H, Kawakami Y, Sakauchi M, Nakamura Y, Takahashi A, Shimano H, Okuda Y, Sewada T, Yamada N. Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice. Biochem Biophys Res Commun. 2001;2:562–568.
    1. De Bandt M, Ben Mahdi MH, Ollivier V, Grossin M, Dupuis M, Gaudry M, Bohlen P, Lipson KE, Rice A, Wu Y, Gougerot-Pocidalo MA, Pasquier C. Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF-RII, suppresses joint destruction in the K/BxN model of rheumatoid arthritis. J Immunol. 2003;9:4853–4859.
    1. Ravelli A, Manzoni SM, Viola S, Pistorio A, Ruperto N, Martini A. Factors affecting the efficacy of intraarticular corticosteroid injection in knees in juvenile idiopathic arthritis. J Rheumatol. 2001;28:2100–2102.
    1. Marti P, Molinari L, Bolt IB, Saurenmann RK. Factors influencing the efficacy of intra-articular steroid injections in patients with juvenile idiopathic arthritis. Eur J Pediatr. 2008;167:425–430. doi: 10.1007/s00431-007-0525-9.
    1. Maricar N, Callaghan MJ, Felson DT, O’Neill TW. Predictors of response to intra-articular steroid injections in knee osteoarthritis – a systematic review. Rheumatology. 2013;52:1022–1032. doi: 10.1093/rheumatology/kes368.
    1. Padeh S, Passwell H. Intraarticular corticosteroid injection in the management of children with chronic arthritis. Arthritis Rheum. 1998;7:1210–1214.
    1. Cunnington J, Marshall N, Hide G, Bracewell C, Isaacs J, Platt P, Kane D. A randomized, double-blind, controlled study of ultrasound-guided corticosteroid injection into the joint of patients with inflammatory arthritis. Arthritis Rheum. 2010;7:1862–1869.
    1. Bjerkoff DJ, Miller LE, Block JE. Clinical utility of ultrasound guidance for intra-articular knee injections: a review. Clin Interv Aging. 2012;7:89–95.

Source: PubMed

3
Subscribe