Decreased clinical response to infliximab in Ankylosing Spondylitis (AS) is correlated with anti-infliximab formation

Mirjam K. de Vries ^1*, Gerrit Jan Wolbink ², Steven Stapel ², Henk de Vrieze ², J Christiaan Van Denderen ³, Ben A.C. Dijkmans ¹, Lucien Aarden ² and Irene E van der Horst-Bruinsma ¹

¹ VU University Medical Center, Netherlands
² Sanquin Research, Netherlands
³ Jan van Breemen Instituut, Netherlands

^* To whom correspondence should be addressed. E-mail: mk.devries{at}vumc.nl.

Accepted 19 April 2007

Abstract

Objectives: Correlation of serum trough infliximab levels and antibodies to infliximab (anti-infliximab) with clinical response in Ankylosing Spondylitis (AS).

Methods: According to the international assessments in Ankylosing Spondylitis (ASAS) consensus statement patients were treated with infliximab (5 mg/kg) every 6 weeks after a starting regimen. Preinfusion sera were collected at baseline, 24 and 54 weeks. During every visit ASAS 20% response was assessed, additionally laboratory tests were performed.

Results: After 24 weeks of treatment 24 patients out of 38 (63%) fulfilled ASAS 20% response criteria and 21 (53%) after 54 weeks. After 54 weeks 11 (29%) patients showed undetectable serum trough infliximab levels and detectable anti-infliximab; six of these patients developed an infusion reaction. Anti-infliximab was significantly more often found in ASAS 20% non-responders compared to responders at week 54 (p=0.036). The serum trough infliximab levels of patients with anti-infliximab were significantly lower (mean: 0.02 mg/l) than in patients without anti-infliximab (mean: 12.7 mg/l) (p<0.0001).

Conclusions: In AS, high levels of serum trough infliximab correlated with a good clinical response. Detection of anti-infliximab within 54 weeks is associated with undetectable serum trough infliximab levels, a reduced response to treatment and an increased risk of developing an infusion reaction.

Keywords: antibodies to infliximab, infliximab, spondylitis, ankylosing, tumor necrosis factor-alpha

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