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Open Access Research article

Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study

Aatke van der Maas1*, Bart JF van den Bemt2, Gertjan Wolbink3, Frank HJ van den Hoogen12, Piet LCM van Riel4 and Alfons A den Broeder1

Author Affiliations

1 Department of Rheumatology, Sint Maartenskliniek, Hengstdal 3, 6522 JV, Nijmegen, The Netherlands

2 Department of Pharmacy, Sint Maartenskliniek, Hengstdal 3, 6522 JV, Nijmegen, The Netherlands

3 Department of Rheumatology, Reade, Dr. Jan van Breemenstraat 2, 1056 AB, Amsterdam, The Netherlands

4 Department of Rheumatology, Radboud University Nijmegen Medical Center Geert Grooteplein-Zuid 10, Postbus 9101, 6500 HB, Nijmegen, The Netherlands

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BMC Musculoskeletal Disorders 2012, 13:184  doi:10.1186/1471-2474-13-184

Published: 24 September 2012

Abstract

Background

To get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort study

Methods

In a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (<1 mg/l) and high (>5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis.

Results

147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (<1 mg/L) and 14% (95%CI 5–22) high trough levels (>5 mg/L). Interestingly also in RA patients with DAS28 ≤ 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels.

Conclusions

Low (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in selected patients.

Keywords:
Rheumatoid arthritis; Infliximab; Therapeutic drug monitoring; Serum trough levels; Anti-infliximab antibodies; Low disease activity