Optimizing Anti-TNF-α Therapy: Serum Levels of Infliximab and Adalimumab Are Associated With Mucosal Healing in Patients With Inflammatory Bowel Diseases

Abstract

In a retrospective study, we found significant association between serum levels of anti-tumor necrosis factor agents and level of mucosal healing. We propose that serum levels of 6-10 μg/mL for infliximab and 8-12 μg/mL for adalimumab are required to achieve mucosal healing in 80%-90% of patients with IBD, and that this could be considered as a "therapeutic window." Exceeding these levels produces only a negligible gain in proportion of patients with mucosal healing.

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

“…An IFX level above 5 µg/ml [area under the curve (AUC) = 0.75, p < 0.0001] and an ADA level above 7.1 µg/ml (AUC = 0.7, p = 0.004) had a specificity of 85% for achieving mucosal healing. [Ungar et al 2015b]. Interestingly, the gained benefit from increasing the drug level achieved a plateau (for IFX levels above 8 µg/ml were associated with only minimal additional gain in mucosal healing, while the correlation between higher ADA levels and increased mucosal healing rate reached a plateau at 12 µg/ml).…”

Higher Adalimumab Drug Levels Are Associated with Mucosal Healing in Patients with Crohn’s Disease

“…Only limited data are available regarding the relationship of adalimumab concentrations, and antibodies to adalimumab [ATA], with favourable clinical outcomes and specifically with mucosal healing. 4,5,6,7 Based on these preliminary data, higher adalimumab levels and absence of ATA during maintenance therapy are associated with mucosal healing in IBD [ Tables 1 and 2 with a combined accuracy of 81.7% when based on the previously described cut-off of 4.9 μg/ml. 4,7 This, along with data from other recent studies, suggests that a threshold of 4.9 μg/ml may not be sufficient to achieve mucosal healing or deep remission.…”

“…Exposure-response studies of anti-TNF therapy, based on therapeutic drug monitoring [TDM], show that favourable therapeutic outcomes, such as mucosal healing, are associated with high serum drug concentrations and undetectable anti-drug antibodies. 3,4,5,6,7,8,9 However, the majority of these studies, as well as two recently published meta-analyses, refer mainly to infliximab. 3,4,5,6,7,8,9,10,11 .…”

“…4,7 This, along with data from other recent studies, suggests that a threshold of 4.9 μg/ml may not be sufficient to achieve mucosal healing or deep remission. 5,6,7 …”

Monitoring Anti-Tnf Drug Treatment in Inflammatory Bowel Disease. Is it Useful in Clinical Practice?

“…The presence of aTNF-ab was greater in patients with no mucosal healing [67]. The recently published study by Ungar et al [68] confirmed this relationship between drug levels and mucosal healing in Crohn's disease.…”