Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis.
OBJECTIVE
To evaluate the associations between (1) antidrug antibody (ADAb) and therapeutic response, (2) ADAb and serum drug trough levels and (3) serum drug levels and therapeutic responses in rheumatoid arthritis (RA) patients receiving adalimumab or etanercept. Secondarily, we aim (1) to evaluate the concordance between radioimmunoassay and bridging ELISA for ADAb assessment and to evaluate the correlation between two different ELISA methods for detecting drug levels, and (2) to determine the optimal cut-off drug levels for good European League Against Rheumatism (EULAR) response.


METHODS
ADAb levels were determined by bridging ELISA and radioimmunoassay, and drug levels evaluated using sandwich ELISA among 36 adalimumab-treated patients and 34 etanercept-treated patients at the 6th and 12th month. The optimal cut-off drug levels for EULAR responses were determined by receiver-operating characteristic curve analysis.


RESULTS
ADAb was detected in 10 (27.8%) and 13 (36.1%) of adalimumab-treated patients after 12-month therapy using bridging ELISA and radioimmunoassay respectively, but not detected in any of etanercept-treated patients. The presence of ADAb was associated with lower EULAR response and lower drug levels compared with those without ADAb (both p<0.001). Drug trough levels were positively associated with DAS28 decrement (ΔDAS28) (all p<0.001). The optimal cut-off trough levels for adalimumab were 1.274 μg/mL and 1.046 μg/mL, and those for etanercept were 1.242 μg/mL and 0.800 μg/mL for good EULAR response assessed at the 6th and 12th month, respectively.


CONCLUSIONS
ADAb levels were inversely correlated with therapeutic response and drug levels. The positive correlation between drug levels and ΔDAS28 indicates that drug monitoring would be useful to evaluate therapeutic response of TNF-α inhibitors.
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan.
Der-Yuan
DY
Chen
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan.
Yi-Ming
YM
Chen
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wen-Chan
WC
Tsai
Division of Allergy, Immunology, and Rheumatology, College of Chinese Medicine, China Medical University, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Jui-Cheng
JC
Tseng
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan.
Yi-Hsing
YH
Chen
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
Chia-Wei
CW
Hsieh
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan.
Wei-Ting
WT
Hung
Division of Immunology and Rheumatology, College of Chinese Medicine, China Medical University Hospital, Taiwan.
Joung-Liang
JL
Lan
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068879:Adalimumab; D000068800:Etanercept
Rheumatoid Arthritis; TNF-alpha; Treatment