Successful treatment of active ankylosing spondylitis with the anti–tumor necrosis factor α monoclonal antibody infliximab

Abstract

Objective. Tumor necrosis factor (TNF) has been detected in sacroiliac joint biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNF monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). Methods. Eleven patients with AS of short duration (median 5 years, range 0.5-13 years) that had been active for at least 3 months (range 3-72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted >1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. Results. One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spon-dylodiscitis) as detected by MRI; followup MRI 2-6 weeks after the third infusion revealed improvement in 2. Improvement of >50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41-94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range <6-90.8) to normal, and the median IL-6 level from 12.4 mg/liter (range 0-28.4) to normal (<5). There was improvement in all 9 SF-36 concepts; the improvement was significant for 6 concepts. Conclusion. These data suggest that anti-TNF therapy is very effective for several weeks in AS. Whether this therapy, in addition to its antiinflamma-tory effect, prevents ankylosis remains to be determined .

Six‐month results of a double‐blind, placebo‐controlled trial of etanercept treatment in patients with active ankylosing spondylitis

“…Anti-TNF␣ therapy with infliximab is approved for Crohn's disease, which is closely linked to AS (14). As recently shown by our group in an open trial (15,16) and in a randomized trial (17), anti-TNF␣ therapy is also very efficacious in active AS.…”

Transmembrane TNF-α, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn's disease

“…[2][3][4][5] The polyps are usually multiple and sessile but may appear as a confluent plaque. They are found throughout the duodenum with a predilection for the periampullary area.…”

“…Neutralization of tumor necrosis ␣ has potent antiinflammatory and disease-modifying effects in an expanding list of immune-mediated disease, including Crohn's disease, rheumatoid arthritis, psoriasis, and ankylosing spondylitis. [5][6][7][8][9] These results have led to a widespread echoed belief that increased production of TNF-␣, a molecule known to cause inflammation and cell death, is a common pathogenic pathway in immune-mediated diseases, and consequently the development of TNFinhibiting antibodies, proteins, peptides, and small molecules has become a cottage industry.…”

Long-term treatment of refractory posterior uveitis with anti-TNFα (infliximab)

“…5 The chimaeric anti-TNFa monoclonal antibody infliximab (Remicade, ScheringPlough BV, Maarsen, The Netherlands) is currently used in the treatment of autoimmune diseases such as rheumatoid arthritis, 6 Crohn's disease, 7 or ankylosing spondylitis. 8 Moreover, its use for the short-term treatment of refractory posterior uveitis has been recently reported. The present prospective study, performed on a cohort of patients subjected to long-term follow-up, was designed to assess the efficiency and safety of infliximab in the treatment of this type of uveitis.…”