Anti-Tnf Therapeutic Drug Monitoring in Post-Operative Crohn's Disease

Anti-TNF prevents post-operative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence.As part of a study of post-operative Crohn's disease management, some patients undergoing resection received prophylactic post-operative adalimumab. In these patients, serum and faecal adalimumab concentration and serum anti-adalimumab antibodies (AAA) were measured at 6, 12 and 18 months post-operatively. CDAI, CRP and faecal calprotectin (FC) were assessed at 6 and 18 months post-operatively. Body mass index and smoking status were recorded. Colonoscopy was performed at 6 and/or 18 months.Fifty-two patients (32 on monotherapy and 20 on combination therapy with thiopurine) were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence (Rutgeerts ≥ i2) (9.98µg/mL vs 8.43 µg/mL, P = 0.387). Patients on adalimumab monotherapy had a significantly lower adalimumab concentration (7.89 µg/mL) than patients on combination therapy (11.725 µg/mL) (P = 0.001), and were significantly more likely to have measurable AAA (31% vs 17%, P = 0.001). Adalimumab concentrations were lower in patients with detectable AAA compared to those without (3.59 µg/mL vs 12.0 µg/mL, P < 0.001). Adalimumab was not detected in faecal samples. Adalimumab serum concentrations were lower in obese patients compared to non-obese (P = 0.046).Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence post-operatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared to those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients