Background The infliximab (IFX) is a monoclonal chimeric antibody targeting the Tumor Necrosis Factor alpha (TNFα), indicated in the rheumatoid arthritis (RA) treatment. Only two-third of RA patients respond to anti-TNFα therapy. At this time, predictive factors of response to anti-TNFα are missing. Commercial kit for IFX and antibody toward IFX (ATI) detection in the serum is now available
Objectives We assessed the development of ATI during one year of IFX treatment in RA patients treated. We also assessed IFX concentrations during the treatment and investigated correlations between the clinical response and IFX concentration and/or ATI development
Methods In a longitudinal multicentric study including 40 RA patients requiring IFX therapy, we assessed the TNFα, IFX, and ATI serum concentrations at various time points: before treatment (W0), at the 6th week (W6), at the 6th month (W22) and at the 12th month (W54) of treatment. All blood samples were collected just before the infliximab infusion. The mean age was 54.2±13.28 years old, the RA mean duration was 11.4±7.8 years, the initial DAS 28 was 5.31±0.86. The clinical response was evaluated according to the EULAR criteria. Clinical response was good in 32% and 24% at W22 and W54, respectively; moderate in 47% and 48% at W22 and W 54, respectively; and bad in 21 and 28% at W22 and W54, respectively. Concentrations were determined by a commercial ELISA (LisaTracker, BMD, France). The data were analyzed with Kruskall-Wallis test (ANOVA), then by a multiple comparison Dunnett post-hoc and with a significance threshold P<0.05. The non parametric correlations were made with Spearman test.
Results The ATI development (concentration upper than 10 μg/ml) was observed early from W6 in 7% of patients but with a low concentrations (lower than 20 μg/ml). However, at W22 and W54, ATI were respectively detected in 45% and 46% of patients. The IFX concentrations increased in time (P<0.001). Initially, median was 0.04 μg/ml, then 4.3 μg/ml at W6 (P<0.05), then decreased at W22 (0.63 μg/ml, P<0.01) and at W54 (1.08 μg/ml, P<0.01).
We found no correlation between the TNFα concentration and the RA activity assessed by the DAS 28. The initial median serum TNFα concentration was 7.2 pg/ml, increased at W6 to 7.2 pg/ml, and remained high relative at W22 and W54 (P<0.05).
At W22 and W54, we observed detection in the serum detection of IFX or ATI. We did not observe presence of both. At W22 and W54, the ATI distribution was heterogeneous in terms of clinical response (P<0.05) with a higher concentration among non-responders than in responders (P<0.05). At 6 months, the ATI presence in serum increased the risk by two to discontinue IFX treatment. ATI development was not correlated with taking a DMARD or dose methotrexate, or corticosteroids prescription.
Conclusions Our study shows an heterogeneity in the ATI development at W22 and W54. However, IFX concentrations were homogenous at W6 and heterogeneous from W22 to W54. This suggests that ATI development contribute to IFX heterogeneity in IFX therapy for RA patients.
Disclosure of Interest None Declared
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