How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

Table 1 Summary and key points

Combination therapy (thiopurines with anti-TNF) is more efficacious than either agent alone in thiopurine-naïve patients with IBD

Combination therapy confers an increased risk of adverse events, of which NMSC, melanoma and lymphoma are the best studied

The benefit of combination therapy is probably due to both an improvement in anti-TNF pharmacokinetics (reduced immunogenicity and improvement in drug levels) and an independent effect of the IM on disease activity

The pharmacokinetic benefits of combination therapy are most important during the first 12 mo of therapy, but may persist beyond this

The optimal dose of IM in this setting may be lower than that used for IM monotherapy, however further studies are needed to confirm this

The risk of relapse after IM withdrawal is highest amongst patients with active disease and positive biomarkers of inflammation or unfavorable anti-TNF pharmacokinetic profiles

Withdrawal of IM should be considered in patients in deep remission after a period of 12 (or perhaps 24 mo) of combination therapy

TNF: Tumor necrosis factor; IBD: Inflammatory bowel disease; IMs: Immunomodulators; NMSC: Non-melanoma skin cancer.