Treatments no longer in development for rheumatoid arthritis

Open Access
Publisher Website
Google Scholar
Abstract
The effects of anti-CD4 mAb on CD+ T cell survival have also provided insights into the pharmacodynamic approach to T cell directed therapeutic studies. Studies of murine anti-CD4 Ab revealed CD4 T cell depletion (hours to several months) irrespective of the antibody isotype while chimeric anti-CD47 and humanised anti-CDW52 (CAMPATH 1H)8 caused prolonged peripheral blood CD4+ T cell depletion out to five years. The dichotomy between clinical and biological effects of anti-CD4 treatment prompted pharmacodynamic studies of the synovial compartment. With chimeric α-CD4 mAb, cMT412, a reduction in the number of inflammatory cells and adhesion molecules was seen in the tissues that failed to correlate with clinical improvement.9 There were no significant changes in the proportion of the synovial CD4+ cells or CD45 RO memory or CD45 RA+ naive cells after treatment. An insufficient decrease in synovial CD4+ T cells and persistence of cytokines IL1β and TNFα was cited to explain the discrepancy. Persistent synovial infiltration by CD4+ T cells was also observed during profound peripheral T cell depletion with CAMPATH-H treatment.10 More recent, pharmacodynamic studies demonstrated a correlation between the clinical response and percentage of anti-CD4 mAb (M412) coated CD4+ lymphocytes in the synovial fluid.11 The data suggest that the lack of clinical benefit with anti-CD4 treatment probably reflects inadequate dosing or duration of treatment, or both. These results also underscore the importance of the synovium as a window for monitoring particularly when no association between clinical and peripheral biological responses is apparent.

This publication has 19 references indexed in Scilit: