Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease

Abstract

Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn’s disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4‒14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2 μg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1 μg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4–14 days after ADA administration was ≥9.2 μg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1 μg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.

Albumin change predicts failure in ulcerative colitis treated with adalimumab

“…It is hoped that IFX and GLM will be investigated based on accumulated results in future cases. It was also reported that the neutrophil to lymphocyte ratio is useful for predicting the efficacy of anti-TNF-α antibody drugs [ 20 ]. In this study, leukocyte differential analysis was performed, but no significant differences were shown for any of the variables, which may be due to the small sample size and differences in endpoints.…”

Higher Adalimumab Trough Levels Are Associated with Histologic Remission and Mucosal Healing in Inflammatory Bowel Disease

“…However, recent data suggest that serum adalimumab concentrations are stable in the first 9 days after injection and can reasonably predict therapeutic trough drug levels, potentially allowing for earlier decision-making based on non-trough adalimumab levels [51,52]. One study by Kato et al found serum ADA levels are predictive of clinical outcomes regardless of trough timing [53]. This may be helpful for patients on more frequent dosing of adalimumab, while the timing of drug levels may be more important to make for patients requiring longer follow-up.…”

Simulated cost‐effectiveness of a novel precision‐guided dosing strategy in adult patients with Crohn's disease initiating infliximab maintenance therapy

“…TDM strategies are increasingly used by clinicians and allow for personalized dose modification based on patients' clinical data, measurement of biologic trough levels, and presence of antidrug antibodies. [9][10][11][12][13][14] TDM strategies in CD are traditionally classified as either "reactive" or "proactive": Reactive TDM is the measurement of biologic concentration and antibodies at the time of symptomatic recurrence, and proactive TDM is the scheduled monitoring of serum drug concentrations to maintain a pre-specified range regardless of symptoms. Evidence shows that proactive TDM strategies applied during biologic maintenance can improve clinical outcomes and reduce CD-related hospitalizations and surgeries.…”

“…Therapeutic drug monitoring (TDM) is a common strategy to reverse/prevent loss of IFX response by optimizing PK. TDM strategies are increasingly used by clinicians and allow for personalized dose modification based on patients' clinical data, measurement of biologic trough levels, and presence of antidrug antibodies 9–14 . TDM strategies in CD are traditionally classified as either “reactive” or “proactive”: Reactive TDM is the measurement of biologic concentration and antibodies at the time of symptomatic recurrence, and proactive TDM is the scheduled monitoring of serum drug concentrations to maintain a pre‐specified range regardless of symptoms.…”