P585 Preventing Crohn's Disease recurrence after resection with adalimumab: Role of drug and anti-drug antibody levels
E. Wright*1, M. Kamm1, 2, F. Selvaraj3, F. Princen3, P. De Cruz1, A. Hamilton1, K. Ritchie1, E. Krejany1, A. Gorelik1, D. Liew1, L. Prideaux1, I. Lawrance1, J. Andrews1, P. Bampton1, S. Jakobovits1, T. Florin1, P. Gibson1, H. Debinski1, R. Gearry1, F. Macrae1, D. Samuel1, I. Kronborg1, G. Radford-Smith1, W. Selby1, M. Johnston1, R. Woods1, P.R. Elliott1, S. Bell1, S. Brown1, W. Connell1, P. Desmond1, S. Singh3
1St Vincent's Hospital & University of Melbourne, Gastroenterology, Melbourne, Australia, 2Imperial College London, Medicine, London, United Kingdom, 3Prometheus Laboratories, Department of Research and Development, San Diego, United States
Crohn's disease usually recurs after intestinal resection. Adalimumab post-operatively prevents recurrence in a majority of patients, but not in all. The cause of recurrence while on anti-TNF therapy is unknown. Low drug concentration and the development of anti-adalimumab antibodies (AAA) have been implicated in loss of response in established luminal disease, but their relationship to the efficacy of adalimumab in preventing postoperative recurrence is unknown.
Patients undergoing resection of all macroscopic Crohn's disease and receiving prophylactic adalimumab post-operatively were studied. Serum adalimumab levels and AAA were measured by homogenous mobility shift assay in adalimumab treated patients at 6, 12 and 18 months post-operatively. Endoscopic assessment was performed at 6 and/or 18 months post-operatively. IBDQ, CDAI, CRP and faecal calprotectin (FC) were measured at all time points.
Adalimumab levels and AAA were measured over time from the time of surgery in 126 samples from 52 patients. 87 (69%) of samples were from patients on adalimumab monotherapy and 39 (31%) were from those on thiopurine combination therapy. 76 samples were matched to endoscopy: 29 (38%) and 47 (62%) of patients had recurrence (Rutgeerts score ≥ i2) at 6 and 18 months respectively. Combining 6 and 18 month endoscopic outcomes adalimumab concentration did not differ significantly between those in endoscopic remission compared to recurrence (10.0µg/mL vs 8.4µg/mL, p = 0.387). An adalimumab level of 9.3 was determined as the optimal cut-off for the prevention of endoscopic recurrence (Sensitivity 0.71, Specificity 0.51, PPV 0.33, NPV 0.84, AUROC 0.56). Of 4 patients with undetectable drug levels 2 were in remission and 2 had recurrent disease. Adalimumab drug level inversely correlated with FC (r = -0.2, p=0.038) but not with CRP (r = -0.11, p=0.364) or Rutgeerts score (r=0.04, p=0.734). AAA were present in 28% of all samples and 80% of samples with undetectable adalimumab level. AAA were more prevalent in those on monotherapy versus combination therapy (34% vs 13%, p=0.012). Median adalimumab levels were lower in patients with detectable AAA compared to those without (3.6µg/mL vs 12.0µg/mL, p<0.001).
Adalimumab drug levels post-operatively did not correlate with endoscopic recurrence after Crohn's disease resection. Drug levels did, however, correlate with FC, raising the possibility that higher drug levels prevent microscopic inflammation. Anti-adalimumab antibodies had a high prevalence and were associated with lower drug levels, suggesting that this may result in subsequent loss of protective effect and disease recurrence with prolonged treatment.