Background Infliximab (IFX) is a monoclonal antibody against tumour necrosis factor α that is effective for treating spondyloarthritis (SpA). However, after initial success of the drug some patients lose responsiveness or develop infusion reactions, which may be related to the development of antibodies against the drug.
Objective To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period.
Methods 94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate ≥1.3 and <2.1, high ≥2.1–≤3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years).
Results ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55±0.89 vs 1.79±1.04, p=0.038 at 6 months; 1.95±0.67 vs 1.67±0.71, p=0.042 at 1 year; 2.52±0.99 vs 1.53±0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853–82 437) vs median 2454 AU/ml, IQR 449–7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011).
Conclusion In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.
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Funding This study was funded by unrestricted medical grant from Pfizer Laboratories of Spain and Proteomika SL. This work was also supported by Ministerio de Ciencia e Innovación grant SAF 2009-07100, and by RETICS Program, RD08/0075 (RIER) from “Instituto de Salud Carlos III” (ISCIII).
Competing interests AB has received fees from Roche, Schering-Plough, Wyeth, Abbott, BMS and USB. EM-M is a consultant and a member of speakers' bureaus for Pfizer, MSD, UCB and Abbott. CP, DP-S, GB and LN have received speaker honoraria from Pfizer. All other authors have declared no conflicts of interest.
Patient Consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.