Determination of lower cut‐off levels of adalimumab associated with biochemical remission in Crohn's disease

Abstract

Background and Aim Adalimumab is administered and dosed using a standardized treatment regimen. Although therapeutic drug monitoring (TDM) may help optimize treatment efficacy, the lower cut‐off concentration of adalimumab needed to retain disease remission has not been established. This cross‐sectional study of patients with Crohn's disease on stable medication aimed to determine a lower therapeutic drug concentration threshold of adalimumab associated with biochemical disease remission. Methods C‐reactive protein (CRP) and fecal calprotectin were used as established markers and albumin as an explorative marker of disease activity. Time since introduction, treatment interval, drug dosage, serum drug concentration and antidrug antibodies, disease duration, age, and sex were recorded. Results The study included 101 patients who were divided into “active disease” and “remission” groups for inflammatory markers based on cut‐off levels of 5 mg/L for CRP and 50 mg/kg for fecal calprotectin. Cut‐off levels for albumin of 36.5 and 41.5 g/L were also added as further indicatives of remission. Receiver operating characteristic analysis found optimal thresholds for adalimumab associated with remission at 6.8–7.0 mg/L for the combination of CRP and fecal calprotectin and when combining CRP, fecal calprotectin, and albumin. Conclusions In patients with Crohn's disease, serum adalimumab of at least 6.8 mg/L was associated with biochemical disease remission based on CRP and fecal calprotectin, supporting the use of TDM to ensure disease control. Albumin should be further tested in this setting.

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

“…Numerous exposure-response relationship studies suggest that biologic drug concentration thresholds and ranges seem to differ depending on treatment goals (Table 6), disease phenotypes, and assays used (2)(3)(4)(5)(31)(32)(33)(39)(40)(41)81,(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118). In general, higher drug concentrations tend to be associated with more stringent outcomes such as endoscopic and histologic remission (2-5), while even higher drug concentrations may be needed for IBD phenotypes characterized by a higher inflammatory burden, such as fistulizing CD (119,120) and acute severe ulcerative colitis (46).…”