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

被引:15
作者
Kharlamova, Nastya [1 ,2 ]
Hermanrud, Christina [1 ,2 ]
Dunn, Nicky [1 ,2 ]
Ryner, Malin [1 ,2 ]
Hambardzumyan, Karen [3 ]
Pomiano, Nancy Vivar [3 ]
Marits, Per [4 ]
Gjertsson, Inger [5 ]
Saevarsdottir, Saedis [3 ,6 ]
Pullerits, Rille [5 ,7 ]
Fogdell-Hahn, Anna [1 ,2 ]
机构
[1] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden
[2] Ctr Mol Med, Stockholm, Sweden
[3] Karolinska Inst, Dept Med, Rheumatol Div, Stockholm, Sweden
[4] Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden
[5] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden
[6] Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland
[7] Sahlgrens Univ Hosp, Dept Clin Immunol & Transfus Med, Gothenburg, Sweden
来源
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
关键词
anti-drug antibody; serum infliximab; clinical threshold value; clinical effect; PandA; ANTITUMOR NECROSIS FACTOR; ALPHA MONOCLONAL-ANTIBODY; RHEUMATOID-ARTHRITIS; CONCOMITANT METHOTREXATE; INFLAMMATORY DISEASES; IMMUNOGENICITY; EFFICACY; THERAPEUTICS; INTERFERENCE; ETANERCEPT;
D O I
10.3389/fimmu.2020.01365
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 mu g/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 mu g/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 mu g/mL. ADA were seldom detected in patients with >1 mu g/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.
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