Azathioprine or 6-Mercaptopurine for Inducing Remission of Crohn's Disease
Azathioprine and 6-mercaptopurine appear not to be effective in inducing remission in Crohn's disease compared with placebo. Infliximab appears to be more effective than azathioprine for induction of remission. Level of evidence: "B"A Cochrane review [Abstract] 1 included 13 RCTs (n=1211) of azathioprine and 6-mercaptopurine therapy in adult patients with Crohn's disease. There was a trend favouring azathioprine or 6-mercaptopurine but no statistically significant difference in clinical remission rates or improvement compared with placebo (table T1). A steroid sparing effect (prednisone dose less than 10 mg/day while maintaining remission) was seen with azathioprine (table T1) There was no difference in adverse events requiring withdrawal. Azathioprine was inferior to infliximab for induction of steroid-free clinical remission and mucosal healing (table T2). The combination of azathioprine and infliximab was significantly superior to infliximab alone for induction of steroid-free clinical remission (table T3). Azathioprine or 6-mercaptopurine therapy was found to be no better at inducing steroid free clinical remission compared to methotrexate and 5-aminosalicylate or sulfasalazine. There were no statistically significant differences in withdrawals due to adverse events between azathioprine or 6-mercaptopurine and methotrexate; between azathioprine or 6-mercaptopurine and 5-aminosalicylate or sulfasalazine; between azathioprine and infliximab; or between the combination of azathioprine and infliximab and infliximab.
Azathioprine (AZA) or 6-mercaptopurine (6-MP) versus placebo for induction of remission in Crohn's disease
| Outcome | Relative effect(95% CI) | Assumed risk - Control - Placebo | Corresponding risk - Intervention: AZA or 6-MP (95%CI) | No of Participants(studies), Quality of evidence |
|---|
| Clinical remission | 1.23 (0.97 to 1.55) | 372 / 1000 | 458 / 1000(361 to 577) | 380(5), Moderate |
| Clinical remission or improvement | 1.26 (0.98 to 1.62) | 359 / 1000 | 452 / 1000(352 to 582) | 434(8), Moderate |
| Steroid sparing effect | 1.34 (1.02 to 1.77) | 457 / 1000 | 612 / 1000(466 to 809) | 143(4), Moderate |
| Withdrawals due to adverse events | 1.70(0.94 to 3.08) | 53 / 1000 | 90 / 1000(50 to 163) | 510(8), Moderate |
Azathioprine (AZA) versus infliximab (IFX) for induction of remission in Crohn's diseas
| Outcome | Relative effect(95% CI) | Assumed risk - Control - AZA | Corresponding risk - Intervention: IFX (95% CI) | No of Participants(studies) Quality of evidence |
|---|
| Clinical remission | 0.66 (0.51 to 0.87) | 479 / 1000 | 316 / 1000(244 to 417) | 339(1), Moderate |
| Clinical remission off steroids | 0.68 (0.51 to 0.90) | 444 / 1000 | 302 / 1000(226 to 400) | 339(1), Moderate |
| Mucosal healing | 0.55 (0.33 to 0.94) | 283 / 1000 | 156 / 1000(93 to 266) | 214(1), Moderate |
| Withdrawals due to adverse events | 1.47 (0.96 to 2.23) | 178 / 1000 | 262 / 1000(171 to 397) | 324(1), Moderate |
Azathioprine + infliximab (AZA+IFX) versus infliximab (IFX) for induction of remission in Crohn's disease
| Outcome | Relative effect(95% CI) | Assumed risk - Control: IFX | Corresponding risk - Intervention: AZA + IFX (95% CI) | No of Participants(studies) Quality of evidence |
|---|
| Clinical remission | 1.26 (1.03 to 1.54) | 479 / 1000 | 603 / 1000(493 to 738) | 338(1), Moderate |
| Clinical remission off steroids | 1.23 (1.02 to 1.47) | 482 / 1000 | 593 / 1000(492 to 708) | 383(2), Moderate |
| Mucosal healing | 1.50 (1.02 to 2.19) | 283 / 1000 | 424 / 1000(289 to 620) | 210(1), Moderate |
| Withdrawals due to adverse events | 1.16 (0.75 to 1.80) | 178 / 1000 | 206 / 1000(134 to 320) | 342(1), Moderate |
References
- Chande N, Townsend CM, Parker CE et al. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2016;(10):CD000545. [PubMed]