icatibant and Osteoarthritis--Knee

Osteoarthritis (OA) is a painful and degenerating progressive disease of the joints which affects millions of patients worldwide. The cause of OA is largely unknown. Among the potential therapies for the symptomatic treatment of OA, the intra-articular administration of a specific bradykinin (BK) B2 receptor antagonist has been reported to produce a long lasting analgesic effect in patients affected by knee OA. BK is a vasodilator and inflammatory nonapeptide which is generated in OA synovium. It contributes to the initiation and maintenance of inflammation, to exciting and sensitizing sensory nerve fibres, thus producing pain, and to activating synoviocytes and chondrocytes which are the main cells involved in the homeostasis of synovial fluid and cartilage, respectively. Moreover, BK synergistically potentiates the effects produced by pro-inflammatory cytokines. Biochemical and preclinical evidence supporting the therapeutic relevance of B2 receptor blockade in OA pathophysiology are reviewed in this publication.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Bradykinin B2 Receptor Antagonists; Chondrocytes; Humans; Inflammation; Injections, Intra-Articular; Kinins; Osteoarthritis, Knee; Pain; Receptor, Bradykinin B2; Synovial Fluid; Synovial Membrane

To evaluate contrast-enhanced ultrasound (CE-US) as a monitoring tool to assess hypervascularisation of synovial processes in knee osteoarthritis (OA) treated with intra-articular injections of the bradykinin-receptor 2 antagonist icatibant compared to contrast-enhanced magnetic resonance imaging (CE-MRI).. In a randomised, double-blind, placebo-controlled trial, 41 patients with painful knee OA underwent US (12.5 MHz for B-mode and 3-8 MHz for CE-US), and 36 of the patients underwent additional MRI (0.2T) at baseline and after 3 injections of the study drug (after a mean of 22.2 days). A total of 15 patients received placebo (group A), 12 patients 500 microg icatibant (group B) and 14 patients 2000 microg icatibant (group C). Pain and the synovial process (B-mode, power Doppler US (PD-US), CE-US, CE-MRI) were assessed at both time points.. At baseline, the placebo group showed more activity in terms of effusion in the superior and lateral recess in ultrasound as well as in PD-US in the lateral recess. Pain improved significantly in all subgroups. Effect sizes were 0.43 (pain at rest) and 0.52 (pain during activity) in group B vs 0.48 and 1.11 in group C. There was no change of US and MRI parameters. We found moderate to good correlation (r) and kappa values (kappa) for effusion in the superior recess (r = 0.591, k = 0.453), effusion in the lateral recess (r = 0.304, k = 0.440) and contrast enhancement (r = 0.601, k = 0.242) between US and MRI.. Our results show that CE-US and CE-MRI have good agreement in assessing inflammatory changes in knee OA. For the 41 patients with OA, an analgesic effect of icatibant could clearly be shown, especially for pain during activity in the high dose icatibant group. However, we could not find an anti-inflammatory effect of icatibant by CE-US compared to CE-MRI.

Topics: Aged; Bradykinin; Bradykinin B2 Receptor Antagonists; Contrast Media; Double-Blind Method; Female; Gadolinium DTPA; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis, Knee; Pain; Phospholipids; Statistics, Nonparametric; Sulfur Hexafluoride; Treatment Outcome; Ultrasonography