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. 2011 Jun 27;13(3):R105.
doi: 10.1186/ar3386.

Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases

Emilie Ducourau  1 , Denis Mulleman, Gilles Paintaud, Delphine Chu Miow Lin, Francine Lauféron, David Ternant, Hervé Watier, Philippe Goupille
Affiliations

Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases

Emilie Ducourau et al. Arthritis Res Ther. .

Abstract

Introduction: A proportion of patients receiving infliximab have antibodies toward infliximab (ATI), which are associated with increased risk of infusion reaction and reduced response to treatment. We studied the association of infliximab concentration at treatment initiation and development of ATI as well as the association of the presence of ATI and maintenance of infliximab.

Methods: All patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving infliximab beginning in December 2005 were retrospectively followed until January 2009 or until infliximab discontinuation. Trough serum infliximab and ATI concentrations were measured at each visit. The patients were separated into two groups: ATI(pos) if ATI were detected at least once during the follow-up period and ATI(neg) otherwise. Repeated measures analysis of variance was used to study the association of infliximab concentration at treatment initiation and the development of ATI. Maintenance of infliximab in the two groups was studied by using Kaplan-Meier curves.

Results: We included 108 patients: 17 with RA and 91 with SpA. ATI were detected in 21 patients (19%). The median time to ATI detection after initiation of infliximab was 3.7 months (1.7 to 26.0 months). For both RA and SpA patients, trough infliximab concentration during the initiation period was significantly lower for ATI(pos) than ATI(neg) patients. RA patients showed maintenance of infliximab at a median of 19.5 months (5.0 to 31.0 months) and 12.0 months (2.0 to 24.0 months) for ATI(neg) and ATI(pos) groups, respectively (P = 0.08). SpA patients showed infliximab maintenance at a median of 16.0 months (3.0 to 34.0 months) and 9.5 months (3.0 to 39.0 months) for ATI(neg) and ATI(pos) groups, respectively (P = 0.20). Among SpA patients, those who were being treated concomitantly with methotrexate had a lower risk of developing ATI than patients not taking methotrexate (0 of 14 patients (0%) vs. 25 of 77 patients (32%); P = 0.03).

Conclusions: High concentrations of infliximab during treatment initiation reduce the development of ATI, and the absence of ATI may be associated with prolonged maintenance of infliximab. Thus, trough serum infliximab concentration should be monitored early in patients with rheumatic diseases.

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Figures

Figure 1
Figure 1
Initial infliximab dose for patients positive and negative for antibodies toward infliximab (ATIpos and ATIneg, respectively). Box plots show the medians and interquartile ranges, and the whisker plots represent the 95th percentiles. Two patients in the RA subgroup (open circles) received 5 mg/kg infliximab at initiation because they were initially suspected of having psoriatic arthritis. During follow-up, anticitrullinated protein antibodies were detected in both patients, which explains their placement in the RA subgroup. Two patients with SpA (open circles) received 3 mg/kg infliximab at initiation because they had a peripheral form of the disease and were therefore misclassified as having RA. ATI: antibodies toward infliximab; ATIpos: ATI detected at least once during follow-up; ATIneg: ATI not detected; RA: rheumatoid arthritis; SpA: spondyloarthritis.
Figure 2
Figure 2
Infliximab concentrations at initiation in ATIpos and ATIneg patients. Box plots show the medians and interquartile ranges, and whisker plots represent the 95th percentiles. ATI: antibodies toward infliximab; ATIpos: ATI detected at least once during follow-up; ATIneg: ATI not detected; RA: rheumatoid arthritis; SpA: spondyloarthritis.
Figure 3
Figure 3
Infliximab maintenance according to ATI status in RA and SpA patients. ATI: antibodies toward infliximab; ATIpos: ATI detected at least once during follow-up; ATIneg: ATI not detected.
Figure 4
Figure 4
Maintenance of treatment by trough infliximab concentration after treatment initiation. RA patients were separated according to (a) the median and (b) the first quartile of trough infliximab concentrations measured at week 14. SpA patients were separated according to the (a) median and (b) the first quartile of trough infliximab concentrations measured at week 14. RA: rheumatoid arthritis; SpA: spondyloarthritis.
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