DOP072 Achieving biochemical remission with adalimumab therapy using therapeutic drug monitoring: Results of a large prospective Crohn's disease cohort. (16th January 2018)

• Record Type: Journal Article
• Authors: Plevris, N; Jenkinson, P; Chuah, C S; Lyons, M; Hall, R; Jones, G; Watson, E; Arnott, I; Lees, C
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 1(2018:Jan.)Supplement 1
• Page Start: S079
• Page End: S080
• Publication Date: 2018-01-16
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjx180.109
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Adalimumab (ADA) is a well-established treatment for Crohn's disease (CD). Despite this limited data are available regarding the relationship of serum ADA levels, and antibodies to ADA (ATA) with clinical outcomes. Methods: We performed a prospective cross-sectional study to investigate the association of serum ADA levels and ATA on clinical outcomes. Inclusion criteria were a diagnosis of CD and minimum of 12 weeks therapy. Patients were written to in advance of their next clinic visit and advised to omit their ADA dose if due within 72 h from their appointment. Serum ADA levels / ATA, CRP and faecal calprotectin (FC) were simultaneously collected at clinic. Biochemical remission was defined as FC < 200 µg/g in addition to CRP < 5 mg/l. Results: At the time of testing, 259 patients were on ADA maintenance therapy (of 356 who had ever received ADA). A total of 195 samples were available for analysis from 178 patients; matched FC and CRP was available for 142/195. Median duration of ADA therapy was 2.4 years (IQR 1.2–4.3) with 37/178 (20.8%) patients receiving concomitant immunosuppression. Median ADA levels were higher in patients receiving weekly ( n = 55) (14.0 µg/ml, 8.0–17.4) vs. fortnightly dosing ( n = 123) (11.0 µg/ml, 7.0–14.5, p = 0.0095). 29/178 (16.3%) patients were positive for ATA. A clear negative correlation was observed between ADA levels and ATA (Spearman's r = −0.567, p < 0.0001). Median ADA levels were 11.0 µg/ml (8.0–14.9), 4.2 µg/ml (2.0–6.0) and 0.0 µg/ml (0.0–2.0) at ATA of < 25 AU/ml, 25–50 AU/ml and >50 AU/ml, respectively ( p < 0.0001). Patients in biochemical remission ( n = 64/142; 45.1%) had significantly higher ADA levels (12.0 µg/ml, 9.0–14.7) than those with active disease (8.9 µg/ml, 5.0–13.2, p = 0.0003). ROC analysis revealed a positive correlation between ADA levels and biochemical remission [AUC (95% CI) 0.67 (0.58–0.75), p = 0.0004]. An optimum ADA level of >8.9 µg/ml was identified for predicting biochemical remission (81.2% sens, 50.0% spec, positive LR 1.6). ADA levels but not ATA independently predicted biochemical remission in a multivariate logistic regression model. Conclusions: Higher ADA levels were independently associated with biochemical remission; levels of >8.9 µg/ml, higher than previously suggested, might be an appropriate target in the maintenance treatment of CD.