Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab

Objective. Tumor necrosis factor alpha (TNF alpha) has been detected in sac roiliac joint biopsy specimens from patients with spondylarthropathy. The p resent open pilot study was undertaken to test the efficacy of the anti-TNF alpha 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 sears) 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 d osage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (C RP) levels (>6 mg/liter) before treatment; these elevations were known to h ave had persisted >1 gear in at least 3 patients. The Bath AS Disease Activ ity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS,lletrology Indes (BASMI) were ass essed. Quality of life was assessed using the Short Form 36 instrument. Lab oratory 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 urtic arial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodisc itis) as detected by MRI; followup MRI 2-6 weeks after the third infusion r evealed improvement in 2, Improvement of greater than or equal to 50% in ac tivity, function, and pain scores was documented in 9 of 10 patients; the m edian 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 pa tients. The median CRP level decreased from 15.5 mg/liter (range <6-90.8) t o normal, and the median IL-6 level from 12.4 mg/liter (range 028.4) to nor mal (<5). There was improvement in all 9 SF-36 concepts; the improvement wa s significant for 6 concepts. Conclusion. These data suggest that anti-TNF alpha therapy is very effectiv e for several weeks in AS. whether this therapy, in addition to its antiinf lammatory effect, prevents ankylosis remains to be determined.