Infliximab (Remicade®) is effective in Reducing the signs and symptoms of Spondylitis
Spondylarthropies are a group of autoimmune disorders of the joint, including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and undifferentiated spondylarthropies. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main course of treatment in spondylarthropies, although the effect of the drugs is only to control pain and stiffness.
No drugs to date have proven to have disease-modifying effects in the spondyloarthropathies. Methotrexate, cyclosporine and sulfasalazine have demonstrated benefit in reducing signs and symptoms in varying subgroups of the spondyloarthropathies. Given the dearth of disease-modifying drugs, recent attention has turned to the potential use of anti-TNF agents in the treatment of spondylarthropies. Van den Bosch et al (Arthritis & Rheum 46(3):755, 2002) examined the efficacy of the anti-TNF agent infliximab versus placebo in the treatment of spondylarthropies.
Methods: Forty patients with active SpA were randomized to receive either intravenous (5 mg/kg) infliximab or placebo at weeks 0, 2, and 6. Evaluations for efficacy and safety were conducted at weeks 1, 2, 6, 8, and 12. The primary endpoints in the study were improvements in the patient and physician global assessments of disease activity on a 100-mm visual analog scale at 12 weeks.
Results: Both primary endpoints improved by week two (P<= 0.05) in the infliximab group when compared with baseline values. The improvements from baseline were even more pronounced by week twelve (P<=0.001). Robust improvements from baseline were also seen in laboratory measures of disease activity (CRP and ESR), night pain scores, numbers of tender and swollen joints and other measures of axial and peripheral disease. One patient developed disseminated tuberculosis and one patient developed a presumed septic arthritis following a joint procedure.
Conclusion: Inhibition of TNF-alpha with infliximab is an effective treatment in patients with active spondylarthropies. The treatment resulted in significant clinical and laboratory improvements and was generally well tolerated. As evidenced by the one instance of disseminated tuberculosis during the study, careful pre-screening for latent and active TB is warranted.
Editorial Comment: The potential pathological role of TNF-ain spondylitis has not been well delineated, in part due to the difficulty of obtaining pathological specimens for investigation. The dramatic response of the infliximab treated patients in this study, and virtual absence of response in the placebo-treated patients, argues strongly for an important role for TNF in the disease.
This study clearly demonstrates dramatic improvements in the signs and symptoms of spondylitis in response to infliximab. Whether the drug will have a disease-modifying effect – that is, slow or prevent calcification and loss of spinal morbidity – will be more difficult to discern. Ankylosing spondylitis is a slowly progressive disease with, as yet, no validated sensitive instruments for assessing progressive ligamentous calcification and ankylosis. In the meantime, comprehensive clinical assessments such as this study by Van den Bosch represent a good start for a very under-investigated disease.