Treatment of Spondyloarthropathy
Treatment of Spondyloarthropathy
Tocilizumab is a monoclonal antibody to the interleukin (IL)-6 receptor. High levels of IL-6 have been demonstrated in serum and synovial tissue of PsA patients. Increased serum levels of IL-6 were also observed in patients with AS. Overexpression of IL-6 was shown in immunohistochemical stains of sacroiliac joints in AS. Interestingly, IL-6 was shown not to have a crucial role in an animal model of AS [human TNF transgenic (hTNFtg) mice]. In the IL-6?/?hTNFtg mice, absence of IL-6 did not alter bilateral, erosive sacroiliitis when compared to hTNFtg littermates.
Although anecdotal reports suggested possible efficacy overall the data suggest tocilizumab may not be effective in SpA, particularly among patients failing TNF inhibitors. Interestingly, there was a biologic response, with clear improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) after treatment, but no clinical significant benefit in axial or peripheral manifestations. Recently, the results of two randomized controlled trials of IL-6 inhibition were presented. In a phase II, multicenter, randomized, double-blind, placebo-controlled study of tocilizumab for 102 patients with AS, no clinical efficacy was observed, although there was significant CRP reduction in the tocilizumab treatment group. Another anti-IL-6R monoclonal antibody, sarilumab, also failed to show clinical efficacy in patients with AS in a phase II, randomized, double-blind, placebo-controlled trial, with no significant difference in ASAS 20 response, ASAS 40 and ASAS partial response criteria between placebo and treatment groups. In a multicenter retrospective observational study, the efficacy of tocilizumab in 21 patients with SpA who failed in TNF-α blocker was evaluated. Tocilizumab could not substantially improve axial SpA symptoms and had inconsistent effects on peripheral SpA.
Interleukin-6 (Tocilizumab)
Tocilizumab is a monoclonal antibody to the interleukin (IL)-6 receptor. High levels of IL-6 have been demonstrated in serum and synovial tissue of PsA patients. Increased serum levels of IL-6 were also observed in patients with AS. Overexpression of IL-6 was shown in immunohistochemical stains of sacroiliac joints in AS. Interestingly, IL-6 was shown not to have a crucial role in an animal model of AS [human TNF transgenic (hTNFtg) mice]. In the IL-6?/?hTNFtg mice, absence of IL-6 did not alter bilateral, erosive sacroiliitis when compared to hTNFtg littermates.
Although anecdotal reports suggested possible efficacy overall the data suggest tocilizumab may not be effective in SpA, particularly among patients failing TNF inhibitors. Interestingly, there was a biologic response, with clear improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) after treatment, but no clinical significant benefit in axial or peripheral manifestations. Recently, the results of two randomized controlled trials of IL-6 inhibition were presented. In a phase II, multicenter, randomized, double-blind, placebo-controlled study of tocilizumab for 102 patients with AS, no clinical efficacy was observed, although there was significant CRP reduction in the tocilizumab treatment group. Another anti-IL-6R monoclonal antibody, sarilumab, also failed to show clinical efficacy in patients with AS in a phase II, randomized, double-blind, placebo-controlled trial, with no significant difference in ASAS 20 response, ASAS 40 and ASAS partial response criteria between placebo and treatment groups. In a multicenter retrospective observational study, the efficacy of tocilizumab in 21 patients with SpA who failed in TNF-α blocker was evaluated. Tocilizumab could not substantially improve axial SpA symptoms and had inconsistent effects on peripheral SpA.
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