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Drug Tolerant Anti-drug Antibody Assay for Infliximab Treatment in Clinical Practice Identifies Positive Cases Earlier

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Kharlamova, Nastya
dc.contributor.author Hermanrud, Christina
dc.contributor.author Dunn, Nicky
dc.contributor.author Ryner, Malin
dc.contributor.author Hambardzumyan, Karen
dc.contributor.author Vivar Pomiano, Nancy
dc.contributor.author Marits, Per
dc.contributor.author Gjertsson, Inger
dc.contributor.author Saevarsdottir, Saedis
dc.contributor.author Pullerits, Rille
dc.contributor.author Fogdell-Hahn, Anna
dc.date.accessioned 2021-01-22T13:20:45Z
dc.date.available 2021-01-22T13:20:45Z
dc.date.issued 2020-07-21
dc.identifier.citation Kharlamova N, Hermanrud C, Dunn N, Ryner M, Hambardzumyan K, Vivar Pomiano N, Marits P, Gjertsson I, Saevarsdottir S, Pullerits R and Fogdell-Hahn A (2020) Drug Tolerant Anti-drug Antibody Assay for Infliximab Treatment in Clinical Practice Identifies Positive Cases Earlier. Front. Immunol. 11:1365. doi: 10.3389/fimmu.2020.01365
dc.identifier.issn 1664-3224
dc.identifier.uri https://hdl.handle.net/20.500.11815/2403
dc.description Publisher's version (útgefin grein)
dc.description.abstract A subgroup of patients treated with infliximab lose response to the treatment and one reason for this is the development of anti-drug antibodies (ADA). If used optimally, measuring drug and ADA level could lead to a more personalized and efficient treatment regime, and enable identification of ADA-positive patients before the underlying disease flares or allergic reactions occur. With the use of a drug-tolerant ADA assay which can detect ADA irrespective of drug levels in the sample, we determined the impact of ADA on treatment failure to infliximab. The aims of this study were to estimate the real-life optimal serum infliximab (sIFX) level and set a clinical threshold value for a drug-tolerant ADA assay. Trough levels of sIFX were measured with ELISA. Free ADA was measured with two drug-sensitive methods (ELISA and a bioassay) and one drug-tolerant method (PandA). Two real-life cohorts treated with infliximab were included; a cross-sectional cohort including patients with inflammatory rheumatic diseases (n = 270) and a prospective cohort of rheumatoid arthritis (RA) patients (n = 73) followed for 1 year. Normal range of sIFX was estimated from the prospective cohort and an arbitrary optimal drug level was set to be between 1 and 6 μg/mL. Using this range, optimal sIFX was found in only 60% (163/270) of the patients in the cross-sectional cohort. These patients had significantly better treatment response than those with a drug level under 1 μg/mL, who had an ADA frequency of 34% (19/56) using the drug-tolerant method. In the prospective cohort, the drug-tolerant assay could identify 34% (53/155 samples) as ADA positive in samples with sIFX level >0.2 μg/mL. ADA were seldom detected in patients with >1 μg/mL sIFX, with three interesting exceptions. A clinically relevant ADA threshold was determined to be >3 RECL as measured with the drug-tolerant assay. In a real-life setting, there was a substantial number of patients with suboptimal drug levels and a proportion of these had ADA. Both too low and too high drug levels correlated with worse disease, but for different reasons. Adding a drug-tolerant assay enabled detection of ADA earlier and regardless of drug level at time of sampling.
dc.description.sponsorship We would like to thank all patients for their participation in this study. We would also like to thank Consuelo Gomez, Pascual Gonzalez, Anna G. Mattsson, Arne St?hl, and Yousra Rehouma for excellent technical assistance. Funding. The research leading to these results has received support from Swelife, Stockholm County Council (ALF project) #20140333 and the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115303, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. This work was also supported by the grants from Aina (Ann) Wallstr?ms och Mary-Ann Sj?bloms Foundation for Medical Research, Professor Nanna Svartz Foundation, the Gothenburg Medical Society (GLS-889421 to RP), the Swedish Rheumatism Association (R-862061 and R-663511 to RP), Adlerbertska research Foundation and the Regional agreement on medical training and clinical research between the Western G?taland county council and the University of Gothenburg (ALFGBG-926621).
dc.format.extent 1365
dc.language.iso en
dc.publisher Frontiers Media SA
dc.relation.ispartofseries Frontiers in Immunology;11
dc.rights info:eu-repo/semantics/openAccess
dc.subject Anti-drug antibody
dc.subject Clinical effect
dc.subject Clinical threshold value
dc.subject PandA
dc.subject Serum infliximab
dc.subject Mótefni
dc.subject Lyfjagjöf
dc.title Drug Tolerant Anti-drug Antibody Assay for Infliximab Treatment in Clinical Practice Identifies Positive Cases Earlier
dc.type info:eu-repo/semantics/article
dcterms.license This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.description.version Peer Reviewed
dc.identifier.journal Frontiers in Immunology
dc.identifier.doi 10.3389/fimmu.2020.01365
dc.relation.url https://www.frontiersin.org/article/10.3389/fimmu.2020.01365/full
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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