Infliximab in patients who have spondyloarthropathy: clinical efficacy, safety, and biological immunomodulation

Spondyloarthropathies (SpAs) are prevalent and disabling diseases that present mainly with spondylitis, pauciarticular peripheral arthritis, and enthesiopathy [1,2]. Ankylosing spondylitis (AS) is the prototype disease in this concept. Other entities include reactive arthritis, psoriatic arthritis (PsA), and arthritis in patients who have inflammatory bowel disease (113D). Spondylitis can affect the whole axial skeleton and results in inflammatory pain and stiffness, with radiographs revealing sacroiliitis, syndesmophytes, and alterations at the zygoapophysial joints, eventually leading to bamboo spine. The arthritis mainly affects the lower limbs with an asymmetric pauciarticular pattern. Dactylitis occurs in some types of SpA, in particular SpA associated with Crohn's disease and psoriasis. Enthesiopathy is a frequent manifestation involving the insertion of the Achilles tendon or the fascia plantaris. In association with intensive physical training, nonsteroidal anti-inflammatory drugs (NSAIDs) are the classical cornerstone of medical therapy in patients who have SpA. The effect of NSAIDs with potent anti-inflammatory activity, such as piroxicam, phenylbutazone, or indomethacin is rapid, but temporary, with relapse of pain upon discontinuation of treatment. The effect of these drugs on disease progression, more specifically the ankylosis, is uncertain. If peripheral arthritis symptoms persist, sulfasalazine can be associated with NSAIDs [3,4]. This therapy is significantly less effective for spondylitis symptoms. AS is one of the rheumatic diseases for which no real disease-modifying antirheumatic treatment is available. Challenges in chronic autoimmune arthritis have changed dramatically, especially since biotechnological compounds have become available. These compounds allow for a specific intervention in the immune cascade underlying the disease. Tumor necrosis factor (TNF)-alpha blocking agents (monoclonal antibodies or soluble receptors) are the first representative drugs in this category, and they have already shown clinically significant efficacy in treating rheumatoid arthritis (RA) [5-7]. Not only do these compounds have a superior effect on the signs and symptoms of the arthritis compared with classical disease-modifying antirheumatic drugs, they also have a structure-modifying action. This action is best illustrated for infliximab in association with methotrexate in patients who have RA. This proof of concept of therapeutic efficacy with biotechnologically engineered compounds in arthritis has given an enormous impetus to the research in this field. Not only are the existing compounds tested in an increasing number of indications, but other agents that interfere selectively with different molecules in the inflammatory cascade are being developed. Together, this puts the rheumatologist in the forefront of a new era of molecular medicine. In this article the authors highlight the recent progress that has been made in the therapy of SpA patients with infliximab (Remicade), a chimeric anti-TNF-alpha monoclonal IgG1 antibody that neutralizes the soluble cytokine and blocks the membrane-bound cytokine [8]. Clinical efficacy of infliximab treatment in patients who have AS and other types of SpA, and safety and biological immunomodulation are also reviewed.