Addition of thiopurines can recapture response in patients with Crohn's disease who have lost response to anti‐tumor necrosis factor monotherapy

• DOI: 10.1111/jgh.12263
• Publication Date: 2013-05-10T15:44:51Z
• Authors: David E H Ong; Michael A Kamm; Juanda Leo Hartono; Mark Lust
• Keywords: Adult; Male; Drug Substitution; Mercaptopurine; Tumor Necrosis Factor-alpha; Adalimumab; Anti-Inflammatory Agents; Antibodies, Monoclonal; Drug Synergism; Antibodies, Monoclonal, Humanized; Infliximab; 3. Good health; Young Adult; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Crohn Disease; Humans; Female; Treatment Failure; Immunosuppressive Agents

AbstractBackground and AimAnti‐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.MethodsFive 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.ResultsAll 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.ConclusionsAddition 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.