In the last 15 years the management of
inflammatory bowel disease has evolved greatly, largely through the increased use of
immunomodulators and, especially, anti-
tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination
therapy with an
immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both
immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination
therapy patients. It has been assumed that these target levels are applicable to patients on combination
therapy also, however there are few data to support this. Similarly, the timing and
duration of treatment with
immunomodulators when used in combination
therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination
therapy. This review will instead focus on how best to optimize
immunomodulators when used in combination
therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of
immunomodulator therapy in combination
therapy patients.