Background: Little is known about the association between the pharmacokinetic features of adalimumab (ADL) and disease outcome in patients with inflammatory bowel disease (IBD).
Aims: To assess the association between random serum ADL levels and clinical and biochemical remission and between ADL levels and clinical decision making in daily practice. To determine the cut-off value for successful dose reduction in IBD patients treated with ADL.
Methods: We conducted a prospective cohort study (18 months) of IBD patients who received maintenance therapy with ADA (at least 12 weeks).
Results: Data were available for 157 serum samples from 87 patients. Serum ADL levels were associated with clinical remission: median 9.2 μg/ml vs 6.0 μg/ml for Crohn's disease patients with active disease (p=0.009) and 14.4 μg/ml vs 5.2 μg/ml for ulcerative colitis patients with active disease (p=0.002) (Fig. 1).
Serum ADL levels were 9.2 μg/ml for patients with a normal C-reactive protein (CRP) value (<5mg/l) and 5.2 μg/ml for patients with a high CRP value (p=0.002) (Fig. 2).
ADL levels were significantly associated with normal fecal calprotectin values (<80 ng/g) (10.8 μg/ml vs 7.6, respectively, p=0.038) (Fig. 3).
We analyzed the clinical decisions taken on the basis of serum ADA levels according to the cut-off values described in previous studies (8 μg/ml).
Figure 4 describes patients' drug levels according to the clinical decision taken. Serum ADL levels were significantly associated with successful de-intensification compared with the group in which doses remained unchanged (AUC 0.88; 95% CI: 0.81–0.95; p<0.001). The cut-off value for successful de-intensification was 12.2 μg/ml.
Conclusions: Higher ADL levels were significantly associated with clinical and biochemical remission. Our results, which were obtained under conditions of daily clinical practice, suggest that an ADL cut-off of 12.2 μg/ml is appropriate for successful dose reduction in IBD patients treated with ADL.