Editorial: drug monitoring targets for optimising adalimumab in Crohn's disease

The reasons for loss of response to adalimumab are poorly understood. Previous studies of infliximab have shown that measuring drug and antibody-to-infliximab concentrations may be valuable tools for optimising TNF-inhibitors.1, 2 In their cross-sectional study,3 Mazor and colleagues presented new evidence regarding the relationship between adalimumab trough concentrations, antibodies to adalimumab (ATA), and clinical outcomes in Crohn's disease (CD). Specifically, they proposed targets for adalimumab monitoring that are associated with clinical remission. In their study of 118 samples from 71 patients, adalimumab drug and ATA were inversely related to disease activity measured by physician's global assessment and CRP. Clinical assessment is limited by the fact that CRP may miss mucosal inflammation in a third of patients with CD,4 A concentration ≥ 5.85 μg/mL had the optimal sensitivity and specificity for remission (68.6%, 70.6%, respectively). A value of ATA ≥3 μg/mL-eq had a specificity of 98% (95% CI 95.5–100%) for active disease. ATA and adalimumab trough concentrations had modest significant associations with CRP (r = 0.29, P = 0.002 and r = −0.425, P < 0.001). These associations may be influenced by the study population, who were largely in remission, and that samples were collected at unselected troughs rather than at time when a patient experienced a flare. About 30.5% of sera had ATA; however, the smaller proportion of antibody positive patients is unknown. Other factors that confound outcomes such as body mass index, albumin and prior anti-TNF exposure were not reported. The lack of data regarding the timing of initiation of immunomodulators limits the ability to interpret their impact. Despite these limitations, little published data beyond abstracts regarding the optimal trough concentrations for adalimumab exists. Mazor and colleagues have proposed specific targets for optimising the efficacy of adalimumab therapy. These targets, and strategies utilising them, remain to be validated and further understood in larger clinical trials5 of therapeutic monitoring in clinical practice. In addition, important clinical questions of how and when to assess these measures, how to optimise therapy based on the results, and how other factors contribute to these complex interactions require further study. Declaration of personal interests: Jason M. Swoger: has served as a consultant for Abbvie, TNI Biotech and Genentech. Barrett G. Levesque: has severed as a speaker for UCB Pharma and Warner Chilcott, and a consultant for Prometheus Laboratories Inc and Nestle Health Sciences and Takeda and Santarus and Abbvie, and is an employee of Robarts Clinical Trials. Declaration of funding interests: None.

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