Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Antibodies towards Infliximab Are Associated with Poor Infliximab Maintenance and Low Infliximab Concentrations.

Ducourau3,  Emilie, Ternant2,  David, Mulleman3,  Denis, Mammou3,  Saloua, Lin3,  Delphine Chu Miow, Watier1,  Hervé, Paintaud2,  Gilles

Universite François Rabelais de Tours, Laboratoire d'Immunologie
Universite François Rabelais de Tours, Laboratoire de Pharmaco-Toxicologie
Universite François Rabelais de Tours, Service de Rhumatologie

Background:

Despite its benefits, infliximab is responsible for the development of antibodies against infliximab (ATI), which is associated with an increased risk of infusion reactions and a reduced response to treatment [1,2]. Herein, we studied the relationship between ATI and infliximab maintenance.

Methods:

All patients initiating infliximab from December 2005 to January 2009 were followed until the end of their treatment or until January 2009. Infliximab [3] and ATI serum concentrations were measured by enzyme linked immunosorbent assays before each infusion. The patients were separated into two groups: "ATIpos" if ATI were detected at least once during the follow-up period or "ATIneg" in the other patients. The characteristics (sex, age, disease, mean disease duration, concomitant treatment with methotrexate or prednisone, infliximab dose at initiation, ESR and CRP) of the 2 groups were compared using a student's t-test or a chi-square test. Infliximab treatment maintenance in the 2 groups was studied using a survival analysis and compared with a log rang test. A P value of less than 0.05 was considered statistically significant.

Results:

A total of 111 patients were studied: 17 rheumatoid arthritis (RA), 91 ankylosing spondylitis (AS), and 3 others systemic diseases. ATI were detected in 22 patients (7 RA, 14 AS and 1 other disease). Median detection of ATI was 3.5 months (0.4–26.0). Infliximab dose at initiation was lower in ATIpos patients than in ATIneg patients (4.1 mg/kg vs. 4.9 mg/kg; p = 0.005). Proportion of patient with concomitant MTX treatment was lower in ATI+ group than ATI- group but the difference did not reach significant difference (14% vs. 36% p = 0.08). Maintenance of infliximab was poorer in ATIpos group than in ATIneg group, with medians of 10 and 16 months, respectively (p = 0.05). Infliximab trough concentrations during initiation were statistically lower in ATI pos than in ATI neg (see Table).

RAATIpos (n=7)ATIneg (n = 10)p
C infliximab (mg/L)   
w27.7 [2.8–16.9]27.2 [7.1–41.9]0.002
w60.3 [0–6.2]15.4 [2.7–35]0.001
w140 [0–0.03]5.4 [0–21.9]0.01
SAATIpos (n = 14)ATIneg (n = 77)p
C infliximab (mg/L)   
w225 [4–40.7]35.8 [14.3–57.2]0.003
w611.9 [0–24.2]29.5 [3.4–69]<0.001
w121.6 [0–13.5]15.8 [0.7–47.3]<0.001
Except where indicated otherwise, values are the median [range]

Conclusion:

In our experience, 20% of patients treated with infliximab develop ATI, often within the first 3 months of treatment. High concentrations of infliximab during initiation seem to reduce the incidence of ATI, and absence of ATI is associated with prolonged durations of infliximab treatment. This clearly argues for an early monitoring of infliximab serum concentrations.

References:

1BaertEngl, FN J Med. 2003;348:601–8.

2Radstake, T, Ann Rheum Dis 2009;68:1739–45.

3Ternant, D, Ther Drug Monit 2006, 28:169–174.

To cite this abstract, please use the following information:
Ducourau, Emilie, Ternant, David, Mulleman, Denis, Mammou, Saloua, Lin, Delphine Chu Miow, Watier, Hervé, et al; Antibodies towards Infliximab Are Associated with Poor Infliximab Maintenance and Low Infliximab Concentrations. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :988
DOI: 10.1002/art.28755

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