Summary of findings for the main comparison. Azathioprine or 6‐mercaptopurine compared to placebo for maintenance of surgically‐induced remission in Crohn's disease.
| Azathioprine or 6‐mercaptopurine compared to placebo for maintenance of surgically‐induced remission in Crohn's disease | ||||||
| Patient or population: People with surgically‐induced remission in Crohn's disease Setting: Outpatient Intervention: Azathioprine (100‐150 mg/day) or 6‐mercaptopurine (1 mg/kg/day ‐ 50 mg/day) Comparison: Placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with Azathioprine or 6‐mercaptopurine | |||||
|
Clinical relapse Follow‐up: 12 to 36 months |
Study population | RR 0.79 (0.67 to 0.92) | 408 (3 RCTs) | ⊕⊕⊕⊝ MODERATE1 | Clinical relapse defined as: a CDAI>250 (D'Haens 2008); a CDAI>150 and 100 point increase from baseline (Mowat 2016) or a grading score > 2 (Hanauer 2004). | |
| 642 per 1,000 | 508 per 1,000 (430 to 591) | |||||
|
Endoscopic relapse Follow‐up:12 to 36 months |
Study population | RR 0.85 (0.64 to 1.13) | 321 (2 RCTs) | ⊕⊕⊝⊝ LOW 2 3 | Endoscopic relapse defined as an endoscopic score i ≥2 (D'Haens 2008; Mowat 2016) | |
| 752 per 1,000 | 639 per 1,000 (481 to 849) | |||||
| Radiologic relapse | Outcome not reported | Not reported | ||||
| Surgical relapse | Outcome not reported | Not reported | ||||
|
Adverse events Follow‐up: 12 to 24 months |
Study population | RR 1.36 (0.57 to 3.27) | 168 (2 RCTs) | ⊕⊕⊝⊝ LOW 4 | Reported adverse events include hair loss, leukopenia, diarrhoea, abdominal pain, hepatotoxicity and arthralgia | |
| 99 per 1,000 | 134 per 1,000 (56 to 323) | |||||
|
Serious adverse events Follow‐up:12 to 36 months |
Study population | RR 1.78 (0.39 to 8.18) | 327 (2 RCTs) | ⊕⊕⊝⊝ LOW 5 | Reported serious adverse events include arthralgia, pancreatitis, leucopenia and bowel obstruction | |
| 13 per 1,000 | 23 per 1,000 (5 to 108) | |||||
|
Withdrawal due to adverse events Follow‐up:12 to 36 months |
Study population | RR 0.90 (0.63 to 1.29) | 408 (3 RCTs) | ⊕⊕⊕⊝ MODERATE6 | Adverse events leading to withdrawal included abnormal blood results leading to temporary discontinuation of treatment in 28% of the participants. However, specific details on reasons for discontinuation were not clearly stated | |
| 254 per 1,000 | 228 per 1,000 (160 to 328) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the median risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; | ||||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1 Downgraded one level due serious imprecision (233 events).
2 Downgraded one level due to serious inconsistency ( I² = 64%).
3 Downgraded one level due to serious imprecision (227 events).
4 Downgraded two levels due to very serious imprecision (20 events) and 95% CI which includes appreciable benefit and harm
5 Downgraded two levels due to very serious imprecision (7 events) and 95% CI which includes appreciable benefit and harm
6 Downgraded one level due to serious imprecision (100 events) and 95% CI which includes appreciable benefit and harm