Table 10.
GRADE Evidence Profile comparing the combination of biologics + immunomodulators (thiopurines, methotrexate) with biologic monotherapy for induction and maintenance of remission in patients with moderate to severe luminal Crohn’s disease.
| INFLIXIMAB + THIOPURINES COMPARED TO INFLIXIMAB MONOTHERAPY 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 infliximab monotherapy | Risk with infliximab + thiopurines | |||||
| Achieving clinical remission (CRITICAL) | 122/196 (62.2%) | 92/200 (47.5%) | RR 0.77 (0.64 to 0.92) | 143 fewer per 1,000 (from 224 fewer to 50 fewer) | 396 (2 RCTs) | ⨁⨁⨁◯1 MODERATE |
| Maintenance of clinical remission (CRITICAL) | 112/196 (57.1%) | 84/200 (42.0%) | RR 0.74 (0.60 to 0.90) | 149 fewer per 1,000 (from 229 fewer to 57 fewer) | 396 (2 RCTs) | ⨁⨁◯◯1,2 LOW |
| INFLIXIMAB + METHOTREXATE COMPARED TO INFLIXIMAB MONOTHERAPY 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 infliximab monotherapy | Risk with infliximab + methotrexate | |||||
| Achieving clinical remission (CRITICAL) | 14/63 (22.2%) | 15/63 (23.8%) | RR 1.07 (0.57 to 2.03) | 16 more per 1,000 (from 96 fewer to 229 more) | 126 (1 RCT) | ⨁⨁◯◯3 LOW |
| Maintenance of clinical remission (CRITICAL) | 17/63 (27.0%) | 20/63 (31.7%) | RR 1.18 (0.68 to 2.03) | 49 more per 1,000 (from 86 fewer to 278 more) | 126 (1 RCT) | ⨁⨁◯◯3 LOW |
| ADALIMUMAB + THIOPURINES COMPARED TO ADALIMUMAB MONOTHERAPY 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 adalimumab monotherapy | Risk with adalimumab + thiopurines | |||||
| Achieving clinical remission (CRITICAL) | 20/85 (30.8%) | 28/91 (30.8%) | RR 1.31 (0.80 to 2.14) | 73 more per 1,000 (from 47 fewer to 268 more) | 176 (1 RCT) | ⨁◯◯◯3,4,5 VERY LOW |
| Maintenance of clinical remission (CRITICAL) | 24/85 (28.2%) | 29/91 (31.9%) | RR 1.13 (0.72 to 1.78) | 37 more per 1,000 (from 79 fewer to 220 more) | 176 (1 RCT) | ⨁◯◯◯3,4,5 VERY LOW |
|
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 | ||||||
Rated down for imprecision since optimal information size not met (<200 events)
Rated down for indirectness (since patients had active disease at baseline, rather than quiescent disease)
Rated down for very serious imprecision due to very wide 95% CI (unable to rule out significant risk of harm with intervention)
Rated down for risk of bias (unblinded study, very high rates of discontinuation due to treatment intolerance as compared to other studies)
Rated down for indirectness (used endoscopic remission as surrogate since primary outcome of clinical remission could be biased due to open-label design)