Treatment of Spondyloarthropathy
Purpose of review Inhibitors of tumor necrosis factor (TNF) have demonstrated dramatic clinical efficacy in patients with spondyloarthropathy (SpA). However, not all patients respond, and some patients who initially improve, subsequently lose response. Therefore, there is still an unmet clinical need for additional therapies. Herein we describe the recent data on newer treatments for SpA patients.
Recent findings Treatments targeting various cytokines, cell surface molecules, and signaling molecules have been assessed. The effects of taregeting B cells with rituximab, T-cell costimulation with abatacept, and interleukin (IL)-6 with tocilizumab have been disappointing in ankylosing spondylitis (AS). Abatacept appears to have a modest effect in patients with psoriatic arthritis (PsA). Targeting IL-17 with secukinumab, IL-12/23 with ustekinumab, and phosphodiesterase 4 (PDE4) with apremilast may prove to be promising treatments for SpA.
Summary There are several newer therapies that may emerge for SpA, particularly those targeting IL-17, IL-23/IL-12, and PDE4.
Prior to the introduction of inhibitors of tumor necrosis factor (TNF), options for the treatment of ankylosing spondylitis (AS) were limited. Traditional 'disease-modifying antirheumatic drugs (DMARDs)', which have clear efficacy in rheumatoid arthritis (RA), were clearly ineffective in the treatment with patients with axial symptoms of spondyloarthropathy (SpA). Several DMARDs, such as sulfasalazine and methotrexate, did show some effect in the treatment of peripheral arthritis in patients with SpA. After the introduction of TNF inhibitor in the treatment of AS, the treatment paradigm was changed. TNF inhibitor has been highly successful in controlling inflammation in many patients with AS. However, not all patients respond, and not all responding patients reach remission. For example, about half of the patients treated with TNF inhibitor showed 50% improvement of disease by the composite Bath Ankylosing Spondylitis Activity Index (BASDAI) outcome measure. Interestingly, the success of TNF inhibitor treatment has raised the goals for treatment of SpA, and hence increased the unmet clinical need for additional approaches to therapy. Recently, data have begun to emerge for targets other than TNF in patients with SpA. Several points should be considered in interpreting data from trials of newer therapies in SpA. TNF inhibitors have emerged as perhaps a gold standard of therapy in SpA. Therefore, for newer therapies, it is of interest to know how they perform in patients who had already been treated with TNF inhibitors; this is the biggest area of unmet clinical need at present. However, patients failing TNF inhibitors are likely to be more refractory to other classes of therapy.
Abstract and Introduction
Abstract
Purpose of review Inhibitors of tumor necrosis factor (TNF) have demonstrated dramatic clinical efficacy in patients with spondyloarthropathy (SpA). However, not all patients respond, and some patients who initially improve, subsequently lose response. Therefore, there is still an unmet clinical need for additional therapies. Herein we describe the recent data on newer treatments for SpA patients.
Recent findings Treatments targeting various cytokines, cell surface molecules, and signaling molecules have been assessed. The effects of taregeting B cells with rituximab, T-cell costimulation with abatacept, and interleukin (IL)-6 with tocilizumab have been disappointing in ankylosing spondylitis (AS). Abatacept appears to have a modest effect in patients with psoriatic arthritis (PsA). Targeting IL-17 with secukinumab, IL-12/23 with ustekinumab, and phosphodiesterase 4 (PDE4) with apremilast may prove to be promising treatments for SpA.
Summary There are several newer therapies that may emerge for SpA, particularly those targeting IL-17, IL-23/IL-12, and PDE4.
Introduction
Prior to the introduction of inhibitors of tumor necrosis factor (TNF), options for the treatment of ankylosing spondylitis (AS) were limited. Traditional 'disease-modifying antirheumatic drugs (DMARDs)', which have clear efficacy in rheumatoid arthritis (RA), were clearly ineffective in the treatment with patients with axial symptoms of spondyloarthropathy (SpA). Several DMARDs, such as sulfasalazine and methotrexate, did show some effect in the treatment of peripheral arthritis in patients with SpA. After the introduction of TNF inhibitor in the treatment of AS, the treatment paradigm was changed. TNF inhibitor has been highly successful in controlling inflammation in many patients with AS. However, not all patients respond, and not all responding patients reach remission. For example, about half of the patients treated with TNF inhibitor showed 50% improvement of disease by the composite Bath Ankylosing Spondylitis Activity Index (BASDAI) outcome measure. Interestingly, the success of TNF inhibitor treatment has raised the goals for treatment of SpA, and hence increased the unmet clinical need for additional approaches to therapy. Recently, data have begun to emerge for targets other than TNF in patients with SpA. Several points should be considered in interpreting data from trials of newer therapies in SpA. TNF inhibitors have emerged as perhaps a gold standard of therapy in SpA. Therefore, for newer therapies, it is of interest to know how they perform in patients who had already been treated with TNF inhibitors; this is the biggest area of unmet clinical need at present. However, patients failing TNF inhibitors are likely to be more refractory to other classes of therapy.
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