The Downside Risk Regarding (-)-MK 801 Maleate A 205804 That No One Is Mentioning

Activation of broblast like synoviocytes produces a broad array of cell (-)-MK 801 Maleate surface and soluble mediators that assist to recruit, retain, and activate cells in the immune method and resident joint cells, foremost for the promotion of ongoing inammation and tissue destruction.

B cells produce autoantibodies, could act as antigen presenting cells, secrete proinammatory (-)-MK 801 Maleate cytokines such as IL 6, and regulate T cells. In addition to possibly acting as antigen presenting cells, B cells produce immunoglobulins and secrete cytokines, perpetuating inammation. Depletion of B cells is a logical therapeutic strategy that should provide a reduction in immunoinammatory components. B cell related potential targets include B lymphocyte stimulator and the proliferation inducing ligand APRIL. Both assist the survival, proliferation, and antigen presentation of B cells. An exploratory phase IB trial of the recombinant fusion protein atacicept, which binds and neutralises B lymphocyte stimulator and APRIL, was recently completed.

Other areas of research include modulating complement activation to prevent the inux of inammatory cells into the synovium and inhibiting chemokines to prevent PARP the degradation of cartilage and bone. The receptor activator of NF ?B/receptor activator of NF ?B ligand pathway is also being targeted with the aim of regulating the formation and activation of osteoclasts. Lastly, although it is still unclear whether patients who fail one TNF blocker should switch to another TNF blocker or to a drug with a dierent mechanism of action, in RA in the recent past it has been common to try another TNF blocker after treatment with the rst TNF blocker has failed. However, it is possible that TNF is not the crucial cytokine instigating RA in primary nonresponders to anti TNF therapy.

In the event of inadequate ecacy with a TNF inhibitor, some have suggested that switching patients to rituximab is a more eective management strategy than switching to another TNF inhibitor. A prospective cohort study of 318 RA patients found that when the motive for switching to rituximab was TNF inhibitor ineectiveness, disease improvement was signicantly better than with an alternative TNF inhibitor. If the reason for switching is not lack of ecacy, there is no advantage in switching to rituximab.