Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation.
OBJECTIVE
Correlation of serum trough infliximab levels and antibodies to infliximab (anti-infliximab) with clinical response in ankylosing spondylitis.


METHODS
In accordance with the international ASsessment 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. At every visit, the 20% improvement response (ASAS-20) was assessed and laboratory tests performed.


RESULTS
24 of the 38 (63%) patients fulfilled ASAS-20 response criteria after 24 weeks of treatment 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 found significantly more often (p = 0.04) in ASAS-20 non-responders compared with responders at week 54. Serum trough infliximab levels were significantly (p<0.0001) lower in patients with (mean 0.02 mg/l) than in those without (12.7 mg/l) anti-infliximab.


CONCLUSIONS
In ankylosing spondylitis, 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, reduced response to treatment and increased risk of developing an infusion reaction.
de Vries
Mirjam K
MK
VU University Medical Centre, Rheumatology department, room 4A-42, PO Box 7057, 1007 MB Amsterdam, The Netherlands. mk.devries@vumc.nl
Wolbink
Gerrit Jan
GJ
Stapel
Steven O
SO
de Vrieze
Henk
H
van Denderen
J Christiaan
JC
Dijkmans
Ben A C
BA
Aarden
Lucien A
LA
van der Horst-Bruinsma
Irene E
IE
D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D015796:HLA-B27 Antigen / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology; D018709:Statistics, Nonparametric; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015796:HLA-B27 Antigen; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab