From: Is there a role of synovial biopsy in drug development?
Drug | Timing of biopsies | Key finding | Reference |
---|---|---|---|
DMARDs/anti-TNF/experimental | 2–16 weeks | Number of CD68+ macrophages in sublining synovial layer is a good biomarker of therapeutic response. | |
Methotrexate | 16 weeks | Decrease in the numbers of inflammatory cells, including CD3+ and CD8+ T cells, CD38+ plasma cells, CD68+ macrophages (lining layer), inflammatory and destructive mediators (Ki67, IL-1β, TNF-α, E-selectin, ICAM-1, VCAM-1, MMP-1). Responders displayed a reduction in the expression of all ICAM-1, VCAM-1, TNF-α and IL-1 β. | |
Methotrexate | 12Â weeks | No change in synovial hyperplasia, lymphoplasmocytic infiltrate, CD68+ macrophages, CD3+ T cells and CD138+ plasma cells | [50] |
Leflunomide | 16 weeks | Decrease in the numbers CD68+ macrophages (sublining), inflammatory and destructive mediators (ICAM-1, VCAM-1, MMP-1). Responders displayed a reduction in the expression of ICAM-1, VCAM-1 and TNF-α. | [81] |
Prednisolone | 24 h | Decrease in the expression of TNF-α (lining and sublining), IL-8 (lining), as well as reduced synovial fluid IL-8 levels. Change in TNF-α correlated with clinical response to, and subsequent relapse after therapy | [82] |
Prednisolone | 2Â weeks | Reduction in the number of sublining synovial macrophages, a trend toward decreased infiltration by CD4+ T cells, CD38+ plasma cells, and CD55+ fibroblast-like synoviocytes | [76] |
Infliximab (3Â mg/kg) | 48Â h/4Â weeks | Reduced number of CD68+ intimal macrophages after 48Â h, a trend to decreased amount of CD38+ plasma cells, CD3+ T cells, sublining CD68+ macrophages after 48Â h/4Â weeks. Decreased numbers of CD3+, CD38+ and both intinal and sublining CD68+ cells were observed in clinical responders after 4Â weeks. | [23] |
Infliximab (10 mg/kg) | 2 weeks | Reduction in the numbers of infiltrating synovial CD3+ T cells, CD22+ B cells, CD68+ macrophages and in the expression of IL-8, MCP-1 and TNF-α. High levels of synovial TNF-α prior to treatment may predict responsiveness to therapy. | |
Rituximab | 4Â weeks | Incomplete depletion of CD22+ B cells, no correlation with the change in DAS28. | [62] |
Rituximab | 4Â weeks 16Â weeks | CD19+ B cells significantly but incompletely decreased at 4Â weeks, with further reduction at 16Â weeks in some patients. Decrease in CD68+ macrophages at 4 and 16Â weeks, CD3+ T cells decreased at 16Â weeks. The reduction of CD138+ plasma cells predicted clinical improvement at 24Â weeks. | [64] |
Rituximab | 12 weeks | Depletion of CD20+ B cells, trend to decrease in CD68+ macrophages. No correlations between changes in CD20+ or CD68+ and changes in the DAS28. Positivity for circulating IgM ACPA, in combination with a high infiltration of CD79a + B cells is a predictor of clinical outcome after rituximab. | |
Tocilizumab | 12Â weeks | Decrease in synovial hyperplasia, lymphoplasmocytic infiltrate, CD68+ macrophages, CD3+ T cells and CD138+ plasma cells | [50] |
Anakinra + pegsunercept | 4 weeks 52 weeks | Decrease in number of CD3+ T cells and TGFβ expression as biomarker therapeutic response at weeks 4 and 52 of combination therapy. Baseline CD3+ and sublining CD68+ infiltration, VEGF and TGFβ expression were predictive of subsequent structural outcome at 6 or 12 months. | [19] |
CCR1 antagonist | 2Â weeks | Reduction in overall cellularity, number of CD4+ and CD8+ T cells, CD68+ macrophages and the number of CCR1+ cells. | [22] |
RecIL-10 | 12Â weeks | No significant change in number of inflammatory cells or in the scores for the expression of cytokines. | [85] |
IL-1 receptor antagonist | 24Â weeks | Reduction in intimal and sublining CD68+ macrophages and CD3+ lymphocytes. | [86] |
Anti-CCL2 antibody | 6Â weeks | No immunohistologic changes. | [66] |
C5aR-antagonis | 4Â weeks | No immunohistologic changes. | [67] |
IFN-β (18/36/54 million IU/week) | 4 weeks 12 weeks | Decrease in number of CD3+ T cells at 4 weeks and CD38+ plasma cells at 12 weeks along with changes of several inflammatory and destructive molecules (e.g. MMP-1, IL-6 or IL-1β). | [87] |
IFN-β (6.6/132 μg/week) | 24 weeks | No changes in synovial tissue infiltrates. | [68] |