Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial

Abstract

Objective The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severe endoscopic recurrence. Methods This was a 1 year, double-blind, doubledummy, randomised study which took place in 21 gastroenterology centres in Austria, the Czech Republic, Germany and Israel. The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6e24 months without subsequent clinical recurrence and with a Crohn's disease activity index (CDAI) score <200, but with moderate or severe endoscopic recurrence. The study drugs were azathioprine 2.0e2.5 mg/kg/day or mesalazine 4 g/day over 1 year. The primary end point was therapeutic failure during 1 year, defined as a CDAI score $200 and an increase of $60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. Results Treatment failure occurred in 22.0% (9/41) of azathioprine-treated patients and 10.8% (4/37) of mesalazine-treated patients, a difference of 11.1% (95% CI À5.0% to 27.3%, p¼0.19). Clinical recurrence was significantly less frequent with azathioprine versus mesalazine (0/41 (0%) vs 4/37 (10.8%), p¼0.031), whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients (9/41 (22.0%) vs 0%, p¼0.002). The proportion of patients showing $1 point reduction in Rutgeerts score between baseline and month 12 was 63.3% (19/30) and 34.4% (11/32) in the azathioprine and mesalazine groups, respectively (p¼0.023). Conclusions In this population of patients with postoperative CD at high risk of clinical recurrence, superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure. Clinical trial registration number NCT00946946.

The use of azathioprine in Crohn’s disease during pregnancy and in the post-operative setting: a worldwide survey of experts

“…Nevertheless, in a recent 1 year, double blind, randomised study in patients with post-operative Crohn's disease at high risk of clinical recurrence, superiority for azathioprine vs. mesalazine could not be demonstrated for therapeutic failure, defined as a CDAI score ‡200 and an increase of ‡60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. 20 In this study, clinical recurrence was significantly less frequent with azathioprine in comparison with mesalazine [0 ⁄ 41 (0%) vs. 4 ⁄ 37 (11%), P = 0.031], whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprinetreated patients [9 ⁄ 41 (22%) vs. 0%, P = 0.002], which had the effect of levelling the therapeutic failure rate between the two arms. 20 Hence, purine analogues appear to represent an attractive option for patients who can tolerate this drug class.…”

“…20 In this study, clinical recurrence was significantly less frequent with azathioprine in comparison with mesalazine [0 ⁄ 41 (0%) vs. 4 ⁄ 37 (11%), P = 0.031], whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprinetreated patients [9 ⁄ 41 (22%) vs. 0%, P = 0.002], which had the effect of levelling the therapeutic failure rate between the two arms. 20 Hence, purine analogues appear to represent an attractive option for patients who can tolerate this drug class. Indeed, in an 8-year intercept cohort of previous or present thiopurine-using IBD patients, a quarter of the patients discontinued thiopurines within 3 months, mostly due to adverse events; however, if thiopurine use was successfully initiated in the first months, its use was usually extended over many years.…”

Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease

“…Reinisch and colleagues recently reported a double blind, double dummy, randomized trial of oral 5-ASA 4.0 g/day Eudragit L enteric coated tablets (Salofalk Õ ) versus azathioprine (2.02.5 mg/kg/day) for prevention of postoperative relapse of CD [Reinisch et al 2010]. Seventy-eight patients that had undergone ileocolonic resection were followed for 1 year and assessed for the primary endpoint of therapeutic failure, defined by CDAI 200 and an increase of 60 points from baseline, or drug discontinuation due to ineffectiveness or adverse side effects.…”

Prevention of postoperative recurrence of Crohn’s disease: Tripterygium wilfordii polyglycoside versus mesalazine

“…Additionally, 5-ASA might be considered an alternative treatment option for patients with a low, rather than high, risk of clinical recurrence. 24 Most of the patients had a penetrating phenotype or had undergone multiple intestinal resections. Thus, using 5-ASA as the comparator in this study may not have been fair.…”