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Comparison of Point-of-Care and Classical Immunoassays for the Monitoring Infliximab and Antibodies Against Infliximab in IBD

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Abstract

Objective

The primary objective is to assess whether the POC assays to measure infliximab residual trough level in the serum of IBD patients were non-inferior to the ELISA techniques available on the market, and to determine which of them was the most robust. The second is to compare three different ELISA kits for monitoring anti-infliximab antibodies (ATI).

Methods

The assays were carried out on patients’ sera using four ELISA kits from four different suppliers (three with a monoclonal antibody and one polyclonal) and two rapid techniques provided by BÜHLMANN (Quantum Blue®) and R-Biopharm (Ridaquick) for monitoring infliximab levels. ATI were measured by three ELISA sets (Grifols, Theradiag, and R-Biopharm) which have different positivity limits and different units.

Results

We measured infliximab residual level and ATI in the serum of 90 IBD patients (85 treated with infliximab and five with adalimumab). All of the infliximab assays were very well correlated when analyzed with Spearman nonparametric correlation (0.93 ≤ r ≤ 0.99), and the two POC assays were also excellently correlated (r = 0.98). The ATI monitoring kits revealed a correlation ranging from 0.73 to 0.96 when comparing positive and negative patients. When normalizing the quantitative values between the different ELISA tests (expressed arbitrarily by using multiples of the positivity limits defined by each supplier), the Spearman r coefficient ranged from 0.81 to 0.93.

Conclusion

The available evidence allows us to conclude that all of the infliximab monitoring assays correlate well and may be used for IFX monitoring; albeit variations in measured IFX concentration among different assays remain present, these assays could be interchangeable. The ATI monitoring techniques are all capable of detecting ATI-positive patients, but because of the difference in the positivity limits and the measurement units, it is better to follow a patient rate with one definite kit.

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Authors and Affiliations

  1. Laboratoire d’Immunologie et d’Immunomonitoring, CIC Inserm 1408, GIMAP EA3064, CHU Saint-Etienne, Saint-Etienne, France

    Yara Nasser, Rémi Labetoulle, Ines Harzallah, Anne-Emmanuelle Berger & Stephane Paul

  2. Service de Gastro-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France

    Xavier Roblin

Authors
  1. Yara Nasser
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  2. Rémi Labetoulle
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  4. Anne-Emmanuelle Berger
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  5. Xavier Roblin
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  6. Stephane Paul
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Correspondence to Stephane Paul.

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Supplementary Figure 1

Distribution of IFX trough levels between assays in the different quartiles. For the quartile comparison, a one-side Cochrane–Armitage trend test has been used. (TIFF 77 kb)

Supplementary Figure 2

Bland–Altman plots of infliximab trough level comparing different techniques two by two. The difference between the two measurements (µg/mL) is plotted on the Y-axis and the average of the two measurements (µg/mL) on the X-axis. Dotted lines represent the 95% limits of agreement. Gap 1: IFX trough level < 3µg/mL, Gap 2: IFX trough level between 3 and 7µg/mL, Gap 3: IFX trough level >7µg/mL. T: Theradiag ELISA. RB: R-Biopharm ELISA. S:Sanquin ELISA. G:Grifols ELISA. RBP: R-Biopharm POC. BP: Buhlmann POC. (TIFF 236 kb)

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Nasser, Y., Labetoulle, R., Harzallah, I. et al. Comparison of Point-of-Care and Classical Immunoassays for the Monitoring Infliximab and Antibodies Against Infliximab in IBD. Dig Dis Sci 63, 2714–2721 (2018). https://doi.org/10.1007/s10620-018-5144-y

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  • DOI: https://doi.org/10.1007/s10620-018-5144-y

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