Drug trough levels predict therapeutic responses to dose reduction of adalimumab for rheumatoid arthritis patients during 24 weeks of follow-up

• Published in: Rheumatology (Oxford, England) Vol. 55; no. 1; pp. 143 - 148
• Main Authors: Chen, Der-Yuan, Chen, Yi-Ming, Hsieh, Tsu-Yi, Hung, Wei-Ting, Hsieh, Chia-Wei, Chen, Hsin-Hua, Tang, Kuo-Tung, Lan, Joung-Liang
• Format: Journal Article
• Language: English
• Published: England 01.01.2016
• Subjects: Adalimumab - administration & dosage; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - pharmacokinetics; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Dose-Response Relationship, Drug; Drug Monitoring; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Male; Middle Aged; Remission Induction; ROC Curve; Time Factors; Treatment Outcome; therapeutic responses; drug troungh level; rheumatoid arthritis; dose reductio; adalimumab
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kev298

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. 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. 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. 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.