Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Anti-drug antibodies (ADAb) in patients treated with adalimumab have been associated with decreased adalimumab concentrations and loss of clinical response, and therefore treatment discontinuation. A large proportion of patients is immunized against adalimumab, but not in every patient ADAb are detectable due to drug interference. Formation of ADAb at initiation is possibly triggered by low drug levels in the patient and vice versa higher drug levels could possibly leed to tolerance in the patient. Since the presence of ADAb is associated with decreased adalimumab concentrations and treatment discontinuation, these concentrations may give an estimation of the presence of ADAb, however, no cutoff concentration has been investigated yet. This study aimed at determining a cutoff value for adalimumab trough concentration for treatment discontinuation due to the presence of ADAb.
This study was conducted in a prospective observational cohort study of 272 consecutive rheumatoid arthritis (RA) patients treated with adalimumab at the Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, the Netherlands. Patients were treated with adalimumab 40 mg every other week. The dosing schedule was increased to 40 mg every week in patients with an inadequate response, (22 patients before 16 weeks). Blood samples were collected before next injection after 4, 16, 28, 40 and 52 weeks of treatment to measure adalimumab concentrations and to detect the presence of ADAb using an ELISA and RIA (radioimmunoassay, Sanquin, Amsterdam). Patients were followed during one year.
Data were analyzed using ROC curve analysis. Youden index was used to estimate the cutoff value for adalimumab concentration which predicts discontinuation within one year due to ADAb presence versuspatients not discontinuing treatment (ADAb+ and ADAb-) and patients discontinuing treatment for which no ADAb were detected (ADAb-).
The area under the ROC curve (AUC) is 0.8968 (95% CI 0.8391 to 0.9546, p<0.0001). The cutoff concentration which maximizes Youden index is 5.0 mg/L with sensitivity of 77,5%, specificity of 90,9%, a positive predictive value of 30.3% and negative predictive value of 98.8%.
Patients who have adalimumab concentrations lower than 5 mg/L at 16 weeks after start of treatment, have a higher risk of treatment discontinuation within one year due to ADAb formation than patients who have higher concentrations at that time point. A patient whose adalimumab concentration is below 5 mg/L at week 16 has a 30% chance to form detectable antibodies against adalimumab, whereas for a patient above this cutoff value, this chance is only 1.2%.
To cite this abstract in AMA style:Pouw MF, Mulleman D, Nurmohamed MT, Rispens T, Paintaud G, Wolbink G, Ternant D. Adalimumab Concentration at 16 Weeks of Treatment Is Associated with Treatment Discontinuation within One Year [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/adalimumab-concentration-at-16-weeks-of-treatment-is-associated-with-treatment-discontinuation-within-one-year/. Accessed August 14, 2020.
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