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

Abstract

Prevention of clinical relapse (resumption of symptoms of active disease) and endoscopic relapse (signs of mucosal inflammation upon examination with an endoscope) are key objectives in the management of Crohn’s disease. There is no treatment currently available that completely prevents relapse and is without significant side-effects. The purpose of this systematic review was to examine the effectiveness and side effects of purine analogue medications (azathioprine and 6-mercaptopurine) used to prevent relapse in Crohn's patients in surgically-induced remission This review identified seven studies that included a total of 584 participants. One study compared azathioprine to placebo (e.g. a sugar pill). Another study compared 6-mercaptopurine to 5-aminosalicylic acid (5-ASA) or placebo. Three studies compared azathioprine to 5-ASA drugs. One small study compared azathioprine to both 5-ASA and adalimumab (a biological drug that is a tumour necrosis factor-alpha antagonist). One small study compared azathioprine to infliximab (a biological drug that is a tumour necrosis factor-alpha antagonist). The study that compared azathioprine to infliximab (22 patients) found that the effects on the proportion of patients who had a clinical or endoscopic relapse were uncertain. A small study (33 patients) found reduced clinical and endoscopic relapse rates favouring adalimumab over azathioprine. No firm conclusions can be drawn from the two small studies that compared azathioprine to infliximab or adalimumab. Adalimumab may be superior to azathioprine but further research is needed to confirm these results. A pooled analysis of two studies (168 patients) suggests that purine analogues may be superior to placebo for preventing clinical relapse in Crohn's patients in surgically-induced remission. One study (87 patients) found a reduction in endoscopic relapse rates favouring 6-mercaptopurine over placebo. A pooled analysis of five studies (425 patients) found no difference in clinical relapse rates between purine analogues and 5-ASA agents. One study (35 patients) found no difference in endoscopic relapse at 12 months between azathioprine and 5-ASA. Another study (91 patients) found reduced endoscopic relapse rates at 24 months favouring 6-mercaptopurine over 5-ASA patients. Patients taking purine analogues were more likely than 5-ASA patients to discontinue therapy due to side effects. Commonly reported side effects across the studies included leucopenia (a decrease in the number of white blood cells), arthralgia (joint pain), abdominal pain or severe epigastric intolerance, elevated liver enzymes, nausea and vomiting, pancreatitis (inflammation of the pancreas), anaemia (a decrease in the number of red blood cells), exacerbation (worsening) of Crohn's disease, nasopharyngitis (common cold), and flatulence. The results of this review need to be interpreted with caution as they are based on small numbers of patients and the overall quality of the evidence from the studies was rated as low or very low due to lack of precision of the results, inconsistent results across studies and the low methodological quality of some studies. Further research investigating the effectiveness and side effects of azathioprine and 6-mercaptopurine in comparison to other medications in patients with surgically-induced remission of Crohn's disease is warranted.