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Practical application of acid dissociation in monitoring patients treated with adalimumab

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An Erratum to this article was published on 13 June 2014

Abstract

Patients treated with adalimumab (ADL) can induce anti-ADL antibodies (AAA) formation that is associated with low drug levels and clinical non-response. But, in the majority of the assays, the measurement of AAA is hampered by the presence of the drug itself. In support of immunogenicity assessment in clinical samples with subtherapeutic ADL levels, we proved acid pre-treatment for AAA detection with the Promonitor-enzyme-linked immunosorbent assay (ELISA). Were measured AAA after acidification in 32 serum samples with a subtherapeutic ADL trough level. ADL and AAA concentrations were measured by ELISA (Promonitor). The impact of drug concentration on AAA recovery (with or without acidification) was also evaluated by mixing known amounts of ADL (0.25, 0.5 and 1 mg/L) and AAA (100, 200, 300 and 400 AU/mL) from clinical samples in pooled serum. The drug significantly inhibited the detection of AAA in untreated samples. And progressively higher levels of ADL cause increasing inhibition of signal. Acid pre-treatment carried a significant increase in assay response, particularly at lower free ADL concentrations. AAA were detected in the 53 % of the samples after acid dissociation. In seven patients, the positive AAA after dissociation was detected in the first monitoring of ADL and five patients were positive 3 months later for AAA with the standard assay. Monitoring AAA using acid dissociation in patients with subtherapeutic circulating level of ADL could detect precocious problems of bioavailability, assess the immunogenicity of ADL and may be used to optimise dose regimens, thereby preventing prolonged use of inadequate therapy and guide change of treatment.

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Authors and Affiliations

  1. Laboratory Department, Marina Baixa Hospital, Av Jaime Botella Mayor nº7, 03570, Villajoyosa, Alicante, Spain

    Francisca Llinares-Tello & Juan Molina-García

  2. Rheumatology Department, Marina Baixa Hospital, Villajoyosa, Alicante, Spain

    José Rosas-Gómez de Salazar, José Miguel Senabre-Gallego, Gregorio Santos-Soler & Esteban Salas-Heredia

  3. Rheumatology Department, Marina Salud Hospital, Denia, Alicante, Spain

    Carlos Santos-Ramírez

  4. CIO-Universidad Miguel Hernández, Elche, Alicante, Spain

    Xavier Barber-Vallés

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  1. Francisca Llinares-Tello
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AIRE-MB Group

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Correspondence to Francisca Llinares-Tello.

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Group AIRE-MB Association for the Investigation in Rheumatology of the Marina Baixa (AIRE-MB): José Rosas Gómez de Salazar, Esteban Salas Heredia, José Miguel Senabre-Gallego, Gregorio Santos-Soler, Catalina Cano Pérez, Ana Pons Bas, Marisa Lorente Betoret (Rheumatology Department, Marina Baixa Hospital), Francisca Llinares-Tello, Juan Molina García (Laboratory Department, Marina Baixa Hospital); Carlos Santos-Ramírez (Rheumatology Department, Marina Salud Hospital, Denia), Xavier Barber Vallés (CIO-Miguel Hernández University, Elche), Mabel Sánchez Barrioluengo (INGENIO [SIC-UPV], Valencia Polytechnic University).

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Llinares-Tello, F., Rosas-Gómez de Salazar, J., Senabre-Gallego, J.M. et al. Practical application of acid dissociation in monitoring patients treated with adalimumab. Rheumatol Int 34, 1701–1708 (2014). https://doi.org/10.1007/s00296-014-3032-0

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