• anti-TNF;
  • Crohn's disease;
  • inflammatory bowel disease;
  • loss of response;
  • thiopurine;
  • thiopurines


Background and Aim

Anti-tumor necrosis factor (TNF) antibodies are effective in maintaining remission in Crohn's disease. However, a significant proportion of patients lose response to these agents with time. This study aimed to determine whether the introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy results in regained response.


Five patients (four males; aged 22–38 years) with active Crohn's disease, who had an initial response to anti-TNF therapy but had lost response, were commenced on azathioprine or mercaptopurine at standard doses while continuing anti-TNF therapy. All had previously failed thiopurine therapy prior to starting anti-TNF treatment.


All patients experienced improved clinical symptoms within 2–6 months, with benefit sustained over a mean follow-up of 19 months. Two patients with an elevated C-reactive protein at the time of thiopurine addition demonstrated a fall in C-reactive protein. Colonoscopy before and after thiopurine addition in four patients showed improvement in all, with mucosal healing achieved in two. No adverse effects of treatment were noted.


Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.