Table 3.
GRADE Evidence Profile comparing infliximab, adalimumab, certolizumab pegol, vedolizumab and ustekinumab with placebo for induction and maintenance of remission in patients with moderate to severe luminal Crohn’s disease. Note, to calculate absolute effect estimate, we used pooled placebo rate of 20% for induction of remission, and 24% for maintenance of remission
| INFLIXIMAB COMPARED TO PLACEBO FOR MODERATE TO SEVERE LUMINAL CROHN’S DISEASE | ||||||
|---|---|---|---|---|---|---|
| Outcomes | Study event rates (95% CI) | Relative effect (95% CI) | Absolute effect* | No of participants (studies) | Quality of the evidence (GRADE) | |
| Risk with placebo | Risk with infliximab | |||||
| Induction of clinical remission (CRITICAL) | 43/54 (79.6%) | 23/52 (44.2%) | RR 0.54 (0.39 to 0.75) | 92 fewer per 1,000 (from 122 fewer to 50 fewer) | 106 (2 RCTs) | ⨁⨁⨁◯1 MODERATE |
| Maintenance of clinical remission (CRITICAL) | 87/110 (79.1%) | 69/113 (61.1%) | RR 0.77 (0.65 to 0.92) | 55 fewer per 1,000 (from 84 fewer to 19 fewer) | 223 (1 RCT) | ⨁⨁⨁◯1 MODERATE |
| ADALIMUMAB COMPARED TO PLACEBO FOR MODERATE TO SEVERE LUMINAL CROHN’S DISEASE | ||||||
| Outcomes | Study event rates (95% CI) | Relative effect (95% CI) | Absolute effect* | No of participants (studies) | Quality of the evidence (GRADE) | |
| Risk with placebo | Risk with adalimumab | |||||
| Induction of clinical remission (CRITICAL) | 239/263 (90.9%) | 196/268 (73.1%) | RR 0.82 (0.75 to 0.89) | 36 fewer per 1,000 (from 50 fewer to 22 fewer) | 531 (3 RCTs) | ⨁⨁⨁◯1 MODERATE |
| Maintenance of clinical remission (CRITICAL) | 180/210 (85.7%) | 127/212 (59.9%) | RR 0.70 (0.62 to 0.79) | 72 fewer per 1,000 (from 91 fewer to 50 fewer) | 422 (3 RCTs) | ⨁⨁⨁◯1 MODERATE |
| CERTOLIZUMAB PEGOL COMPARED TO PLACEBO FOR MODERATE TO SEVERE LUMINAL CROHN’S DISEASE | ||||||
| Outcomes | Study event rates (95% CI) | Relative effect (95% CI) | Absolute effect* | No of participants (studies) | Quality of the evidence (GRADE) | |
| Risk with placebo | Risk with certolizumab pegol | |||||
| Induction of clinical remission (CRITICAL) | 489/608 (80.4%) | 455/616 (73.9%) | RR 0.92 (0.86 to 0.98) | 16 fewer per 1,000 (from 28 fewer to 4 fewer) | 1224 (3 RCTs) | ⨁⨁◯◯2 LOW |
| Maintenance of clinical remission (CRITICAL) | 443/536 (82.6%) | 393/542 (72.5%) | RR 0.88 (0.83 to 0.93) | 29 fewer per 1,000 (from 41 fewer to 17 fewer) | 1078 (2 RCTs) | ⨁⨁⨁◯3 MODERATE |
| VEDOLIZUMAB COMPARED TO PLACEBO FOR MODERATE TO SEVERE LUMINAL CROHN’S DISEASE | ||||||
| Outcomes | Study event rates (95% CI) | Relative effect (95% CI) | Absolute effect* | No of participants (studies) | Quality of the evidence (GRADE) | |
| Risk with placebo | Risk with Vedolizumab | |||||
| Induction of clinical remission (CRITICAL) | 320/355 (90.1%) | 357/429 (83.2%) | RR 0.92 (0.87 to 0.97) | 16 fewer per 1,000 (from 26 fewer to 6 fewer) | 784 (2 RCTs) | ⨁⨁◯◯2 LOW |
| Maintenance of clinical remission (CRITICAL) | 120/153 (78.4%) | 94/154 (61.0%) | RR 0.78 (0.67 to 0.91) | 53 fewer per 1,000 (from 79 fewer to 22 fewer) | 307 (1 RCT) | ⨁⨁⨁◯1 MODERATE |
| USTEKINUMAB COMPARED TO PLACEBO FOR MODERATE TO SEVERE LUMINAL CROHN’S DISEASE | ||||||
| Outcomes | Study event rates (95% CI) | Relative effect (95% CI) | Absolute effect* | No of participants (studies) | Quality of the evidence (GRADE) | |
| Risk with placebo | Risk with ustekinumab | |||||
| Induction of clinical remission (CRITICAL) | 515/588 (87.6%) | 460/589 (78.1%) | RR 0.90 (0.85 to 0.94) | 96 fewer per 1,000 (from 131 fewer to 53 fewer) | 1177 (3 RCTs) | ⨁⨁⨁◯3 MODERATE |
| Maintenance of clinical remission (CRITICAL) | 137/204 (67.2%) | 101/200 (50.5%) | RR 0.75 (0.64 to 0.89) | 168 fewer per 1,000 (from 242 fewer to 74 fewer) | 404 (2 RCT) | ⨁⨁⨁◯1 MODERATE |
|
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1
Rated down for imprecision since optimal information size not met (<200 events)
2
Rated down for very serious imprecision since effect estimate was smaller than the minimal clinically important difference of at least 10% over placebo
3
Rated down for serious imprecision since 95% CI of effect estimate was smaller than the minimal clinically important difference of at least 10% over placebo