Disease-Modifying Antirheumatic Drugs for Spondyloarthropathies
Disease-Modifying Antirheumatic Drugs for Spondyloarthropathies
The inflammatory arthritides included in the category of spondyloarthropathy (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, undifferentiated spondyloarthropathy, and arthritis associated with inflammatory bowel disease) may cause significant, progressive morbidity. Therapy with nonsteroidal antiinflammatory drugs and traditionally used disease-modifying antirheumatic drugs, such as methotrexate, often fails in patients with more severe peripheral arthropathy and axial involvement, and alternative treatment options have been limited. With increased understanding of the pathologic processes involved in these disorders, new therapeutics have arisen and are being investigated in the various subtypes of spondyloarthropathy. This article reviews recent progress in disease-modifying therapy for spondyloarthropathy, including new biologic response modifiers, such as the tumor necrosis factor-
inhibitors etanercept and infliximab.
The spondyloarthropathies are a group of rheumatic disorders distinct from rheumatoid arthritis that involve chronic inflammation of joints, with or without extraarticular features. Included are the clinical syndromes of ankylosing spondylitis (the prototypic disorder), psoriatic arthritis, reactive arthritis, undifferentiated spondyloarthropathy, and arthritis associated with chronic inflammatory bowel disease. Because of the overlapping clinical features of these disorders, clinical presentation often determines treatment strategy.
Common clinical features of spondyloarthropathies are listed in Table 1 . In addition to synovitis, enthesitis (inflammation at sites where ligaments, tendons, or joint capsules attach to bone) is a hallmark of spondyloarthropathy, distinguishing it from other arthritides. Interestingly, in HLA-B27 transgenic rats that develop spondyloarthropathy-like disease, contrast-enhanced MRI detected inflammatory changes in the tendon, tendon sheaths, joint capsule, subcutaneous tissue, and muscle long before synovitis developed. Advances in MRI technology have also led to the recognition of significant edema (implying inflammation) existing within the subchondral bone and marrow adjacent to the sacroiliac joint and sites of enthesial attachment in patients with spondyloarthropathy.
A scoring system for use with contrast-enhanced MRI has been developed and found reliable in infliximab-treated patients with ankylosing spondylitis. Contrast-enhanced ultrasonography has also improved the detection of active sacroiliitis and enthesopathy and in some circumstances may be superior to MRI. These methods may improve the documentation of disease activity, progression, and treatment response of spondyloarthropathy.
Although the cellular and molecular mechanisms of the spondyloarthropathies are not yet fully understood, characteristics of the inflamed sites include increased numbers of T cells and macrophages and increased expression of proinflammatory cytokines, such as interleukin (IL)-1
, tumor necrosis factor-
(TNF-
), and interferon gamma. With the increased understanding of the immunopathology of SpA and progress in treating an analogous disease, rheumatoid arthritis, therapeutic strategies for spondyloarthropathy have expanded and are currently under investigation in many of the spondyloarthropathy subtypes.
inhibitors etanercept and infliximab.
The spondyloarthropathies are a group of rheumatic disorders distinct from rheumatoid arthritis that involve chronic inflammation of joints, with or without extraarticular features. Included are the clinical syndromes of ankylosing spondylitis (the prototypic disorder), psoriatic arthritis, reactive arthritis, undifferentiated spondyloarthropathy, and arthritis associated with chronic inflammatory bowel disease. Because of the overlapping clinical features of these disorders, clinical presentation often determines treatment strategy.
Common clinical features of spondyloarthropathies are listed in Table 1 . In addition to synovitis, enthesitis (inflammation at sites where ligaments, tendons, or joint capsules attach to bone) is a hallmark of spondyloarthropathy, distinguishing it from other arthritides. Interestingly, in HLA-B27 transgenic rats that develop spondyloarthropathy-like disease, contrast-enhanced MRI detected inflammatory changes in the tendon, tendon sheaths, joint capsule, subcutaneous tissue, and muscle long before synovitis developed. Advances in MRI technology have also led to the recognition of significant edema (implying inflammation) existing within the subchondral bone and marrow adjacent to the sacroiliac joint and sites of enthesial attachment in patients with spondyloarthropathy.
A scoring system for use with contrast-enhanced MRI has been developed and found reliable in infliximab-treated patients with ankylosing spondylitis. Contrast-enhanced ultrasonography has also improved the detection of active sacroiliitis and enthesopathy and in some circumstances may be superior to MRI. These methods may improve the documentation of disease activity, progression, and treatment response of spondyloarthropathy.
Although the cellular and molecular mechanisms of the spondyloarthropathies are not yet fully understood, characteristics of the inflamed sites include increased numbers of T cells and macrophages and increased expression of proinflammatory cytokines, such as interleukin (IL)-1
, tumor necrosis factor-
(TNF-
), and interferon gamma. With the increased understanding of the immunopathology of SpA and progress in treating an analogous disease, rheumatoid arthritis, therapeutic strategies for spondyloarthropathy have expanded and are currently under investigation in many of the spondyloarthropathy subtypes.
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