Anti-tumor necrosis factor (TNF)-α antibodies are effective therapeutic agents to treat inflammatory bowel disease (IBD). In the biologic era, the development of immunogenicity has been a critical issue for secondary loss of response. The superiority of anti-TNF therapy in combination with immunomodulators (IMs) is well-established for infliximab (IFX) but less evident for adalimumab (ADA). To clarify the contribution of thiopurines to ADA-treated patients with Crohn's disease (CD), the deep remission of immunomodulator and adalimumab combination therapy for Crohn's disease (DIAMOND) studies provided the first randomized comparison of efficacy between ADA monotherapy and ADA with thiopurine. The results of the DIAMOND and DIAMOND2 studies revealed the appropriate ADA therapeutic strategy for immunosuppressant-naïve patients with active CD based on therapeutic drug monitoring, endoscopic findings and clinical issues regarding the use of thiopurines.