Therapeutic drug monitoring-guided biological drug therapy in inflammatory bowel disease: Consensus statements of the Australian Inflammatory Bowel Disease Association (AIBDA) and Gastroenterological Society of Australia (GESA)

Abstract

Introduction: Therapeutic drug monitoring (TDM)-guided biological drug therapy in inflammatory bowel disease (IBD) may improve clinical outcomes and reduce treatment cost, beyond fixed or clinically guided dosing. TDM of biological drugs involves measurement of drug levels and antidrug antibodies, and data are most comprehensive for TDM of anti-tumor necrosis factor (TNF) agents. Reactive TDM is performed during treatment failure to elicit mechanisms of failure and guide appropriate treatment changes (dose escalation versus changing to another agent), while proactive TDM is performed routinely in patients who maintain response in order to optimize drug levels and prevent future disease flares and loss of response. We produced consensus statements based on current evidence to aid implementation of TDM-guided therapy of biological drugs in IBD. Methods: Consensus statements were produced via a modified Delphi method. A steering committee invited Australian and international experts in IBD and TDM of biological drugs. A literature search aided the steering committee in producing an initial draft of the consensus statements. Two rounds of online voting were undertaken, with modification of statements following each round based on voting results and feedback. On a final face-to-face voting round, each statement was presented, modified, and voted on. Panelists voted on their level of agreement with individual statements as follows: A) agree without reservation; B) agree with minor reservation; C) agree with major reservation; D) disagree with some reservation; E) disagree without reservation; or F) reserved. Statements with ≥ 80% agreement with no or only minor reservation met criteria for consensus. Level of evidence and grade of recommendation for each statement was agreed upon based on National Health and Medical Research Council (NHMRC) recommendations. Results: Of 26 panel nominees, 25 accepted to participate in this project, including the following: 18 Australian gastroenterologists, 1 IBD Fellow, 1 international gastroenterologist, 1 international gastroenterologist/clinical pharmacologist, 1 international clinical pharmacologist, 1 Australian investigational pharmacist, 1 Australian clinical pharmacologist, and 1 Australian immunologist. All 25 panelists participated in the first two rounds of online voting, and 22 panelists attended the final face-to-face voting round (absentees for personal reasons). Following the final voting round, consensus was reached on 22/24 statements (see Table 1). The agreed NHMRC levels of evidence and grades of recommendation for the consensus statements correlated strongly (Spearman's correlation coefficient, 0.544; P = 0.006). The consensus statements made recommendations on appropriate adalimumab and infliximab therapeutic ranges for clinical remission, scenarios to perform TDM of anti-TNF agents, and interpretation of results. Consensus was stronger for reactive TDM than proactive TDM of anti-TNF agents, reflecting current evidence. Although evidence indicates that TDM can optimize therapy with vedolizumab and ustekinumab, current data are insufficient to recommend routine TDM for non-anti- TNF biological drugs. Conclusion: TDM is part of the clinical assessment to identify the cause behind ongoing symptoms or suboptimal therapy in patients with IBD treated with biological agents. These guidelines should help implement TDM to guide therapy with anti-TNF biologics, including dose escalation, dose reduction, and switching within or out of class. (Table Presented) .L6180065412017-08-31 <br />