The relative resistance of the cadherin-11–null mice to induced arthritis indicates that this molecule might be a therapeutic target. Using complementary approaches with a cadherin-11–specific monoclonal antibody and a cadherin-11–Fc fusion protein, the investigators showed that both reagents suppress the induction of disease. However, the treatment of established disease was less effective than prevention of acute arthritis in mice. Migration and invasion of synoviocytes are clearly affected by the function of cadherin-11. Arthritic cadherin-null mice develop bone erosions; however, synovial attachment and migration of synoviocytes into cartilage were markedly diminished. An opposing picture was previously described in mice deficient in the receptor activator of nuclear factor kappa B ligand (RANKL); these mice developed severe cartilage damage without bone erosion in the same model of induced arthritis. Cartilage damage in the RANKL-deficient mice reflected direct synovial pannus activity rather than a secondary effect from deterioration of the underlying bone. In the cadherin-null mice, there is relative preservation of the cartilage in the face of bone destruction and a dysfunctional synovium.
The precise mechanism for the improvement in anti-cadherin–treated mice has yet to be determined. Do these treatment protocols result in synoviocyte apoptosis, migration, or senescence? The long-term consequences of anti-cadherin therapy to joint organization and integrity also need to be addressed. Disrupting the usual cohesion of hyperproliferative pannus might be a successful strategy in secondarily undermining the ability of immune cells to deliver localized proinflammatory signals. In addition, a treatment that targets the cohesiveness of the synovial architecture might prove to be a useful adjunctive therapy to immunosuppressive therapies without further increasing the risk of severe infections. A synergistic agent with minimal additional risk would be highly beneficial in our therapeutic arsenal.
When Treating Uveitis, All Anti-TNFs May Not Be Equal
By Michael M. Ward, MD
Guignard S, Gossec L, Salliot C, et al. Efficacy of tumor necrosis factor blockers in reducing uveitis flares in patients with spondyloarthropathy: a retrospective study. Ann Rheum Dis. 2006;65:1631-1634.
Abstract
Objective: To evaluate the efficacy of anti–tumor necrosis factor (TNF) treatments (given for rheumatological manifestations) in reducing uveitis flares in patients with spondylarthropathy in daily practice.
Methods: A retrospective observational study of all patients with spondylarthropathy with at least one uveitis flare treated with anti-TNF in one center (Dec. 1997–Dec. 2004). The number of uveitis flares per 100 patient-years was compared before and during anti-TNF treatment; each patient was his or her own control. The relative risk (RR) and the number needed to treat (NNT) were calculated.
