Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease

• Published in: Cochrane database of systematic reviews 2019-08, Vol.8 (8), p.CD010233
• Main Authors: Gjuladin-Hellon, Teuta, Iheozor-Ejiofor, Zipporah, Gordon, Morris, Akobeng, Anthony K
• Format: Article
• Language: English
• Subjects: Azathioprine - therapeutic use; Child health; Crohn Disease - drug therapy; Crohn Disease - prevention & control; Crohn Disease - surgery; CROHN'S DISEASE ‐ MAINTENANCE OF REMISSION; Gastroenterology & hepatology; Humans; Immunosuppressive Agents - therapeutic use; Maintenance Chemotherapy - methods; Mercaptopurine - therapeutic use; Randomized Controlled Trials as Topic; Remission Induction - methods; Secondary Prevention
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.cd010233.pub3

Crohn's disease (CD) is a chronic relapsing inflammatory condition and maintenance of remission is a major issue as many patients fail to achieve remission with medical management and require surgical interventions. Purine analogues such as azathioprine (AZA) and 6-mercaptopurine (6-MP) have been used to maintain surgically-induced remission in CD, but the effectiveness, tolerability and safety of these agents remains controversial. To assess the efficacy and safety of purine analogues (AZA and 6-MP) for maintenance of surgically-induced remission in CD. We searched PubMed, MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 26 July 2018 (and from inception to 31 July 2019). In addition, we searched reference lists of all included studies and relevant reviews, conference proceedings and trials registers. Randomised controlled trials (RCTs) with a duration of at least three months that enrolled adults and children with surgically-induced remission of CD and compared AZA or 6-MP to no treatment, placebo or any other active intervention were considered for inclusion. Two authors independently assessed trial eligibility, extracted data, assessed the risk of bias and assessed the certainty of the evidence using GRADE. The primary outcome was clinical relapse. Secondary outcomes included endoscopic relapse, radiologic and surgical relapse, adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs and health-related quality of life. Ten RCTs with a total of 928 participants were included. Study participants were adults recruited from university clinics and gastroenterology hospitals who received interventions post-surgery for a duration between 12 to 36 months. Most study participants were recruited less than three months after surgery in all except one study where participants were recruited between 6 to 24 months post-surgery. One study was rated as low risk of bias, six studies were rated high risk of bias and three were rated unclear risk of bias.There was moderate certainty evidence that purine analogues are more efficient for preventing clinical relapse than placebo. At 12 to 36 months, 51% (109/215) of AZA/6-MP participants relapsed compared to 64% (124/193) of placebo participants (RR 0.79; 95% CI 0.67 to 0.92; 408 participants; 3 studies; I² = 0%; moderate certainty evidence). The certainty of the evidence regarding the efficacy of AZA or 6-MP for maintaining postoperative clinical remission compar