P347 Undetectable levels of adalimumab in clinical practice: Should we say goodbye to the drug?
S. Bejar1, G. Bastida Paz1,2, M. Aguas1,2, A. Garrido Marín1, R. Marques3, E. Valero Pérez1, J. del Hoyo Francisco1, L. Tortosa Seguí1, D. Muñoz Gómez1, J.L. Poveda3, P. Nos Mateu1,2
1Department of Gastroenterology, La Fe University Hospital, Valencia, Spain, 2Enfermedad Inflamatoria Intestinal, Instituto de Investigación Sanitaria La Fe de Valencia IIS La Fe, Valencia, Spain, 3Department of Pharmacy, La Fe University Hospital, Valencia, Spain
Background
Therapeutic drug monitoring (TDM) is used in inflammatory bowel disease to guide dosing of biologics to individualise drug exposure and optimise outcomes. In case of undetectable levels of Adalimumab (levels <1.6 μg/ml) some authors recommend to discontinue the treatment, although this strategy is not universally accepted. The aim of this study was to describe the evolution (recovery of levels and persistence of treatment) of patients with undetectable levels of ADA and its relationship with the different treatment strategies (dose escalation and/or addition of an immunosuppressant)
Methods
Since October 13 to August 19, 758 TDM were performed in 260 patients treated with ADA. We selected the patients who had at least a level <1.6 μg / ml. Patients with follow-up fewer than 90 days after level detection and those in whom the drug was withdrawn at that time were excluded
Results
We identified 46 patients with undetectable levels; 12 were excluded. Thirty-four patients were included, 29 (85.3%) with Crohn’s disease and 5 (14.7%) with ulcerative colitis. Ten (29.4%) patients had combined treatment and 17 (50%) had previously received another anti-TNF. In 24 (70.6%) TDM was performed proactively. After detection of levels <1.6 μg /ml, ADA was intensified in 20 patients (58.8%) either shortening the interval in 18 (90%), increasing the dose in 8 (40%) or with both interventions in 6 (30%). In 5 (14.7%) patients an immunomodulator was added and in 14 (41.2%) the treatment was not modified. At the end of the follow-up (mean 1101 days; SD 510) 61.8% (21/34) of the patients continued with ADA: 75% (15/20) in the intensified group and 42.9% (6/14) in the group of those who did not receive changes in treatment. Fourteen patients (41. 2%) recovered therapeutic levels (>5 μg/ml), 12 (60%) in the intensified-patient group and 2 (14.3%) in the group in whom the treatment was not modified. ADA was withdrawn in 13 patients (32.8%) after a mean time of 358 days (SD 258). The ADA maintenance rate (HR=3.88; 95% CI 1.2–12.4; p = 0.02) and the recovery ratio of ADA levels (HR = 6.75; 95% CI 1.1–39, 8; p = 0.03) was higher in the intensified group. Hypoalbuminemia was associated with an earlier withdrawal of ADA (p = 0.03)
Conclusion
The intensification of ADA in patients with IBD and undetectable plasma concentrations allows recovery of levels and maintenance of the drug in a high percentage of patients. The decision to withdraw treatment in patients with undetectable levels should be individualised.