Immunogenicity of Infliximab Is Related to Reduction of Frequency of Infliximab Administration in Rheumatoid Arthritis and Spondyloarthritis Patients

Mathieu Verdet¹, Clément Guillou², Marie-Laure Potier², Martine Hiron², Fabienne Jouen³, Olivier Boyer⁴, Thierry Lequerré⁵ and Olivier Vittecoq⁶, ¹Rheumatology, Rouen University Hospital, Bois Guillaume, France, ²Inserm 905 & Institute for Biomedical Research, University of Rouen, Rouen, France, ³Immunology, Rouen University Hospital, Rouen Cedex, France, ⁴Immunology, INSERM U905, University of Rouen, Rouen, France, ⁵Rheumatology Department & Inserm 905, Department of Rheumatology, Rouen University Hospital & Inserm 905, Institute for Biomedical Research, University of Rouen, Rouen, France, ⁶Rheumatology, Rouen University Hospital & Inserm905, University of Rouen, Rouen Cedex, France

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: anti-TNF therapy, Antibodies, infliximab, rheumatoid arthritis, treatment and spondylarthropathy

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Background/Purpose:

To analyze the clinical and biological characteristics associated with presence of antibodies to Infliximab, in rheumatoid arthritis (RA) and spondyloarthritis patients (SpA).

Methods:

Sera from RA (n=22) or SpA (n=23) patients receiving Infliximab have been analyzed with a commercial multiplex enzyme-linked immunosorbent assay kit (LISA-Tracker Infliximab BMD®). Antibodies toward Infliximab (ATI) and Infliximab trough concentrations were measured in their serum. Result was considered positive if ATI concentrations were >10ng/mL. Clinical and biological data were retrospectively collected from the patient’s medical file.

Results:

Infliximab was given in association with methotrexate in 31 patients (69%). The time between two consecutive Infliximab adminstration was higher than 8 weeks in Fifteen patients (33%). Fifteen patients were in remission at time of analysis. Time between two Infliximab administration was significantly longer in patients who had obtained remission(9.27 weeks) compared to other patients(6.83 weeks; Mann-Whitney Test, p=0.0005).

Seven patients(15%) were ATI+. Time since beginning of Infliximab was not different between ATI+ and ATI- patients.

Posology of Infliximab at time of analysis was not different between ATI+ (4.29mg/kg) and ATI- patients(4.13mg/kg; Mann-Whitney Test, p=0.74).

Longer time between infliximab infusions was associated with presence of ATI(ATI +: 9.57 weeks; ATI -: 7.29 weeks; Mann-Whitney Test p=0.02). As expected, Infliximab concentration was significantly lower in ATI+ patients(0.18μg/mL) compared to ATI- patients(2.1μg/mL; Mann-Whitney Test, p=0.0005). There was a significant inverse correlation between ATI titer and Infliximab concentration in the serum(Spearman test, p=0.0001). In contrast, no association was found between the posology of Methotrexate and presence of ATI.

Conclusion:

Immunogenicity against Infliximab was associated to a longer interval between infusions. This result could impact on treatment strategy for patients in clinical remission since decreasing the frequency of Infliximab administration may favor the development of ATI.

Disclosure:

M. Verdet,
None;

C. Guillou,
None;

M. L. Potier,
None;

M. Hiron,
None;

F. Jouen,
None;

O. Boyer,
None;

T. Lequerré,
None;

O. Vittecoq,
None.

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