Update on Anti-Tumor Necrosis Factor Therapy
Purpose of Review: The introduction of the macromolecule tumor necrosis factor inhibitors etanercept, infliximab, and adalimumab has proven very successful for patients with spondyloarthropathies. The greatest experience has accrued in ankylosing spondylitis and psoriatic arthritis. This paper reviews data from clinical trials with tumor necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis.
Recent Findings: Treatment with tumor necrosis factor inhibitors has not only resulted in substantial improvement in the signs and symptoms of arthritis but has also improved functional status and quality of life in ankylosing spondylitis and psoriatic arthritis. Improvements in associated inflammatory features, such as enthesitis in psoriatic arthritis and uveitis in ankylosing spondylitis, have also been observed. Moreover, treatment has been shown to inhibit the progression of radiographic joint damage in psoriatic arthritis and to attenuate spinal inflammation in ankylosing spondylitis. The notable success of tumor necrosis factor inhibitors has not only changed the treatment paradigms for these conditions but has also stimulated studies aimed at improving diagnosis, prognostic stratification, and other aspects of clinical care.
Summary: The introduction of tumor necrosis factor inhibitors for patients with ankylosing spondylitis and psoriatic arthritis has had a tremendous impact on daily clinical care.
Occasionally, a new class of therapies has such a profound impact that it affects not only the treatment paradigms for a disease but also the diagnostic approach and other key aspects of clinical care. Such has been the case with the introduction of tumor necrosis factor (TNF) inhibitors for the treatment of spondyloarthropathies.
The term spondyloarthropathy encompasses several individual diseases, including ankylosing spondylitis, psoriatic arthritis, enterophatic arthritis (spondyloarthropathy associated with inflammatory bowel disease), undifferentiated spondyloarthropathy, juvenile spondyloarthropathy, and reactive arthritis. As a group, these diseases, which are characterized by inflammatory arthritis affecting axial and peripheral joints as well as potential extra-articular inflammation in the skin, gastrointestinal tract, and other organs, have an overall prevalence comparable to that of rheumatoid arthritis. Although immunopathophysiologic distinctions exist between rheumatoid arthritis and spondyloarthropathy, a key common feature is the important role of the proinflammatory cytokine TNF in the initiation and sustenance of articular and systemic inflammation. Combined with the vast and growing clinical experience with TNF inhibitors in rheumatoid arthritis, this provided support for the assessment of these agents in patients with spondyloarthropathy. The rationale for the use of TNF inhibitors in the spondyloarthropathies includes immunopathophysiologic evidence suggesting a key role for TNF; unmet clinical need, including the need for a greater appreciation of the severity and impact of spondyloarthropathies on affected patients and lack of alternative therapies, particularly for spondylitis; and experience with TNF inhibitors in other conditions, particularly rheumatoid arthritis.
Another critical factor leading to the testing and use of TNF inhibitors is the large unmet clinical need in spondyloarthropathy. Whereas these diseases were once considered to be relatively benign, evidence is growing, particularly in psoriatic arthritis and ankylosing spondylitis, that many affected patients manifest significant radiographic joint damage, functional impairment, reduced quality of life, and long-term work disability. Moreover, although they may have a modest effect on peripheral arthritis and certain other aspects of disease, traditional disease-modifying antirheumatic drugs (DMARDs) have been proven ineffective for spinal disease in spondyloarthropathy.
The three currently available TNF inhibitors, etanercept, infliximab, and adalimumab, have been shown not only to significantly improve the signs and symptoms of spondyloarthropathy but also to improve functional status and quality of life and even to attenuate disease progression. The dramatically impressive clinical efficacy of these agents has occurred in parallel with, and to some extent has driven, considerable progress in disease classification and stratification. The overall effect has been to invigorate clinical research and clinical practice in the field. To review recent key developments and to set the stage for future considerations, we focus here on the use of TNF inhibitors in ankylosing spondylitis and psoriatic arthritis, two conditions in which there has been a great deal of recent data.
Purpose of Review: The introduction of the macromolecule tumor necrosis factor inhibitors etanercept, infliximab, and adalimumab has proven very successful for patients with spondyloarthropathies. The greatest experience has accrued in ankylosing spondylitis and psoriatic arthritis. This paper reviews data from clinical trials with tumor necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis.
Recent Findings: Treatment with tumor necrosis factor inhibitors has not only resulted in substantial improvement in the signs and symptoms of arthritis but has also improved functional status and quality of life in ankylosing spondylitis and psoriatic arthritis. Improvements in associated inflammatory features, such as enthesitis in psoriatic arthritis and uveitis in ankylosing spondylitis, have also been observed. Moreover, treatment has been shown to inhibit the progression of radiographic joint damage in psoriatic arthritis and to attenuate spinal inflammation in ankylosing spondylitis. The notable success of tumor necrosis factor inhibitors has not only changed the treatment paradigms for these conditions but has also stimulated studies aimed at improving diagnosis, prognostic stratification, and other aspects of clinical care.
Summary: The introduction of tumor necrosis factor inhibitors for patients with ankylosing spondylitis and psoriatic arthritis has had a tremendous impact on daily clinical care.
Occasionally, a new class of therapies has such a profound impact that it affects not only the treatment paradigms for a disease but also the diagnostic approach and other key aspects of clinical care. Such has been the case with the introduction of tumor necrosis factor (TNF) inhibitors for the treatment of spondyloarthropathies.
The term spondyloarthropathy encompasses several individual diseases, including ankylosing spondylitis, psoriatic arthritis, enterophatic arthritis (spondyloarthropathy associated with inflammatory bowel disease), undifferentiated spondyloarthropathy, juvenile spondyloarthropathy, and reactive arthritis. As a group, these diseases, which are characterized by inflammatory arthritis affecting axial and peripheral joints as well as potential extra-articular inflammation in the skin, gastrointestinal tract, and other organs, have an overall prevalence comparable to that of rheumatoid arthritis. Although immunopathophysiologic distinctions exist between rheumatoid arthritis and spondyloarthropathy, a key common feature is the important role of the proinflammatory cytokine TNF in the initiation and sustenance of articular and systemic inflammation. Combined with the vast and growing clinical experience with TNF inhibitors in rheumatoid arthritis, this provided support for the assessment of these agents in patients with spondyloarthropathy. The rationale for the use of TNF inhibitors in the spondyloarthropathies includes immunopathophysiologic evidence suggesting a key role for TNF; unmet clinical need, including the need for a greater appreciation of the severity and impact of spondyloarthropathies on affected patients and lack of alternative therapies, particularly for spondylitis; and experience with TNF inhibitors in other conditions, particularly rheumatoid arthritis.
Another critical factor leading to the testing and use of TNF inhibitors is the large unmet clinical need in spondyloarthropathy. Whereas these diseases were once considered to be relatively benign, evidence is growing, particularly in psoriatic arthritis and ankylosing spondylitis, that many affected patients manifest significant radiographic joint damage, functional impairment, reduced quality of life, and long-term work disability. Moreover, although they may have a modest effect on peripheral arthritis and certain other aspects of disease, traditional disease-modifying antirheumatic drugs (DMARDs) have been proven ineffective for spinal disease in spondyloarthropathy.
The three currently available TNF inhibitors, etanercept, infliximab, and adalimumab, have been shown not only to significantly improve the signs and symptoms of spondyloarthropathy but also to improve functional status and quality of life and even to attenuate disease progression. The dramatically impressive clinical efficacy of these agents has occurred in parallel with, and to some extent has driven, considerable progress in disease classification and stratification. The overall effect has been to invigorate clinical research and clinical practice in the field. To review recent key developments and to set the stage for future considerations, we focus here on the use of TNF inhibitors in ankylosing spondylitis and psoriatic arthritis, two conditions in which there has been a great deal of recent data.
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