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FRI0304 Treatment of knee osteoarthritis with intra-articular infliximab improves total womac score. High baseline levels of synovial cellularity predict improvement
  1. H.B. Lindsley1,
  2. J. Schue1,
  3. O. Tawfik2,
  4. R. Bolce3,
  5. D.D. Smith1,
  6. G. Hinson4,
  7. J.A. Wick5
  1. 1Internal Medicine
  2. 2Pathology, University of Kansas Medical Center, Kansas City
  3. 3Janssen Services, Horsham
  4. 4Radiology
  5. 5Biostatistics, University of Kansas Medical Center, Kansas City, United States

Abstract

Background Synovial tissue from patients with osteoarthritis (OA) demonstrated synovial inflammation (Benito et al.). We hypothesized that a single intraarticular (IA) injection of an anti-TNF drug would result in decreased inflammatory cell infiltration and ultimately reduce articular injury.

Objectives Evaluate the short-term benefit of IA anti-TNF therapy in knee osteoarthritis.

Methods This study was a single center, 2:1:1 [INF:MP:P] randomization, double-blind, placebo-controlled treatment of knee OA with IA treatments of infliximab (INF) 100 mg, methylprednisolone (MP) 80 mg or saline (P) on Day 0. Subjects (n=16) had to have knee pain and show minimal to moderate osteoarthritic change on plain radiographs. Closed needle synovial biopsies (Bx) were obtained on Days 0 and 28. Total WOMAC was determined at Days 0, 14, 28 and 56. Bivariate associations were investigated using logistic and linear regression.

Results Total WOMAC score improved significantly only for Group INF, comparing baseline to Day 56 (p<0.05) (See Fig). Overall 6 of 16 subjects had high levels of synovial cellularity (level 1-2, scale 0-3) at baseline, 4 of whom were in Group INF. These 4 subjects had the greatest degree of improvement in total WOMAC. Baseline CRP levels (baseline values =0.57-1.21 mg/dl) correlated with total WOMAC scores and did predict improvement (p=0.07). Baseline knee MRI grade (0-5) correlated with baseline total WOMAC but did not predict improvement. Circulating INF levels showed a maximum median concentration at Day 4 (3.70 ug/ml; range 0.56-11.27); two subjects found to have anti-INF antibodies by Day 14 showed reduced levels of INF at Day 14 (median 0.05 ug/ml), compared to the remaining 6 subjects at Day 14 (2.67 ug/ml; range 0.56-3.77). Synovial tissue showed reduction in two markers: CD68 macrophages (3 of 7 Bx INF Group) and CD54 ICAM-1 (2 of 4 Bx MP Group). Flow cytometric studies of PBMCs at Days 0 and 28 showed reduced numbers of INF subjects with TNF-expressing CD20 B cells and CD14 monocytes at Day 28.

Conclusions In this pilot study the Total WOMAC score showed significant improvement by Day 56 (p<0.05) for the INF group. Baseline synovial cellularity and CRP also correlated with improvement. Anti-TNF IA therapy offers promise as symptomatic therapy.

  1. Benito MJ, et al. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005;64:1263-7.

Disclosure of Interest H. Lindsley Grant/Research support from: Janssen, J. Schue: None Declared, O. Tawfik: None Declared, R. Bolce: None Declared, D. Smith: None Declared, G. Hinson: None Declared, J. Wick: None Declared

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