A Personalized Medicine Approach to Biologic Treatment of RA
A Personalized Medicine Approach to Biologic Treatment of RA
The importance of collecting data on the primary site of inflammation, the synovium, to understand the effects of anti-rheumatic treatment is illustrated by the observation that clinical arthritis activity is accompanied by persistent histologic signs of synovitis after treatment with humanized anti-cluster of differentiation 52 (CD52) antibodies or chimeric anti-CD4 antibodies, despite profound depletion of peripheral blood lymphocytes. Similarly, it has for instance been shown that B-lineage cells may persist in the synovium in some RA patients after treatment with rituximab, in spite of marked depletion of peripheral blood B cells in nearly all patients.
Successful treatment with DMARDs, such as gold, MTX, LEF and CSs, has consistently been associated with decreased mononuclear cell infiltration in the synovium. Similarly, successful treatment of RA patients with infliximab, anakinra and rituximab results in reduced synovial inflammation.
In one study, patients were randomly assigned to treatment with prednisolone according to the Combinatietherapie Bij Reumatoide Artritis (COBRA) regimen or placebo for 2 weeks. This study identified synovial sublining macrophages as the best biomarker associated with the clinical response to CSs. Next, the utility of macrophages in the synovial sublining as a candidate biomarker was tested across discrete interventions and kinetics. The consistent relationship between the decrease in synovial macrophages and clinical improvement after anti-rheumatic treatment was also confirmed by other studies. Taken together, these studies indicate that successful treatment of RA results in decreased accumulation of synovial macrophages associated with clinical improvement, independent of the specific mechanism of action (Fig. 2).
(Enlarge Image)
Figure 2.
Clinical signs and symptoms of RA are associated with macrophage infiltration and activation. Different pathogenetic mechanisms may drive this common final pathway. Successful treatment of RA results in decreased accumulation of synovial macrophages associated with clinical improvement, independent of the specific mechanism of action. Mø: macrophage; FLS: fibroblast-like synoviocyte.
Effective Anti-rheumatic Treatments Affect Common Final Pathways
The importance of collecting data on the primary site of inflammation, the synovium, to understand the effects of anti-rheumatic treatment is illustrated by the observation that clinical arthritis activity is accompanied by persistent histologic signs of synovitis after treatment with humanized anti-cluster of differentiation 52 (CD52) antibodies or chimeric anti-CD4 antibodies, despite profound depletion of peripheral blood lymphocytes. Similarly, it has for instance been shown that B-lineage cells may persist in the synovium in some RA patients after treatment with rituximab, in spite of marked depletion of peripheral blood B cells in nearly all patients.
Successful treatment with DMARDs, such as gold, MTX, LEF and CSs, has consistently been associated with decreased mononuclear cell infiltration in the synovium. Similarly, successful treatment of RA patients with infliximab, anakinra and rituximab results in reduced synovial inflammation.
In one study, patients were randomly assigned to treatment with prednisolone according to the Combinatietherapie Bij Reumatoide Artritis (COBRA) regimen or placebo for 2 weeks. This study identified synovial sublining macrophages as the best biomarker associated with the clinical response to CSs. Next, the utility of macrophages in the synovial sublining as a candidate biomarker was tested across discrete interventions and kinetics. The consistent relationship between the decrease in synovial macrophages and clinical improvement after anti-rheumatic treatment was also confirmed by other studies. Taken together, these studies indicate that successful treatment of RA results in decreased accumulation of synovial macrophages associated with clinical improvement, independent of the specific mechanism of action (Fig. 2).
(Enlarge Image)
Figure 2.
Clinical signs and symptoms of RA are associated with macrophage infiltration and activation. Different pathogenetic mechanisms may drive this common final pathway. Successful treatment of RA results in decreased accumulation of synovial macrophages associated with clinical improvement, independent of the specific mechanism of action. Mø: macrophage; FLS: fibroblast-like synoviocyte.