Drug trough levels predict therapeutic responses to dose reduction of adalimumab for rheumatoid arthritis patients during 24 weeks of follow-up.
OBJECTIVE
To evaluate the impact of adalimumab (ADA) dose-halving on therapeutic responses and drug levels, the differences in drug levels among patients with different therapeutic responses and the optimal baseline cut-off ADA levels for predicting persistent remission or low disease activity (LDA) at week 24 of dose-halving therapy in 64 RA patients who had already achieved LDA or remission at baseline.


METHODS
Anti-ADA antibody levels were determined by bridging ELISA, ADA levels were evaluated using sandwich ELISA and therapeutic responses were assessed by the 28-joint DAS change. The optimal cut-off drug levels for predicting persistent remission were determined by receiver operating characteristic curve analysis.


RESULTS
At baseline, 25 (39.1%) and 39 (60.9%) patients had achieved remission and LDA, respectively. After 24 week ADA dose-halving, persistent remission was observed in 23 patients, remission turned LDA in 2 patients, persistent LDA in 24 patients and disease flare in 15 (23.5%) patients. Three patients who developed anti-ADA antibodies at week 24 of dose-halving had very low drug levels and disease flare. Among 61 anti-ADA antibody-negative patients, ADA levels declined by half after 24 weeks of dose-halving (median 5.5 vs 2.6 μg/ml). Baseline ADA levels were significantly higher in patients with persistent remission (median 10.5 μg/ml) or LDA (4.5 μg/ml) than in those with disease flare (0.9 μg/ml), indicating associations of ADA levels with therapeutic responses. An ADA level above the cut-off value of 6.4 μg/ml might predict persistent remission after dose-halving with high sensitivity and specificity.


CONCLUSIONS
ADA dose-halving is feasible for patients who have achieved remission and sufficient drug levels. Drug level monitoring may help clinicians optimize the dosing regimen and prevent overtreatment for patients receiving anti-TNF-α therapy.
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Institute of Microbiology and Immunology, Chung Shan Medical University, dychen@vghtc.gov.tw.
Der-Yuan
DY
Chen
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University.
Yi-Ming
YM
Chen
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University.
Tsu-Yi
TY
Hsieh
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University.
Wei-Ting
WT
Hung
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University.
Chia-Wei
CW
Hsieh
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University.
Hsin-Hua
HH
Chen
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University.
Kuo-Tung
KT
Tang
Division of Immunology and Rheumatology and College of Medicine, China Medical University, Taichung, Taiwan.
Joung-Liang
JL
Lan
D000068879:Adalimumab / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D000068879:Adalimumab
adalimumab; dose reductio; drug troungh level; rheumatoid arthritis; therapeutic responses