List of relevant RCT data on early intervention in CD
| Author (Year) | Study design | Intervention/control | Early CD definition | Primary outcome | Significant results |
| Panes et al18 (2013) | RCT | Azathioprine versus placebo | <8 weeks | Steroid-free remission at month 76 | No differences in the primary outcome (p=0.48) |
| Cosnes et al19 (2013) | Open-label RCT | Early azathioprine versus conventional therapy | <6 months | Steroid-free and anti-TNF-free remission at month 76 | No differences in the primary outcome (p=0.69) Early intervention associated with less perianal surgery (p=0.03) |
| Colombel et al16 (2015) | Post hoc analysis of the SONIC trial | Combination of infliximab and azathioprine in early versus late CD | ≤18 months | Steroid-free remission at week 26 | Shorter disease duration was associated with 81% vs 80% CR rates (p=0.036) 63% vs 53% achieved the composite endpoint of CR and MH (p=0.03) 65% vs 44% achieved CR+MH+normal CRP (p=0.001) |
| Colombel et al24 (2014) | Subanalysis from the EXTEND trial | Adalimumab maintenance stratified by disease duration (<2 years; 2–5 years; >5 years) | <2 years | Deep remission | 33% vs 20% vs 16% of patients in deep remission (p value=NA) |
| Schreiber et al37 (2013) | Subanalysis of the CHARM trial | Adalimumab versus placebo | <2 years | CR at week 56 | Shorter disease duration associated with CR at week 56 (OR 0.97, p=0.046) |
| D’Haens et al17 (2008) | RCT | Top-down versus step-up approach | 6 months | CR at week 104 | Higher remission rates in the TD group at week 52 (p=0.0278), but not 104 (p=0.43) 73.1% vs 30.4% of MH (p=<0.001) in favour of the TD approach |
| Khanna et al46 (2015) | RCT | Early intervention versus conventional approach | NA | CR at month 24 | ET strategy was associated with significant lower risk of surgery (HR=0.69, p=0.0314), serious disease complications (HR=0.73, p=0.0005) and combined hospital admission, disease complications and hospitalisation rate (HR=0.73, p=0.0003) |
| Safroneeva et al (2015)38 | Prospective observational cohort | Early use of anti-TNF and/or immunomodulators | 24 months | Development of complications | Early treatment was associated with reduced risk of bowel strictures (HR 0.496, p=0.004 for IM; HR 0.276, p=0.018 for anti-TNF) Early immunosuppression was associated with reduced risk of intestinal surgery (HR 0.322, p=0.005), perianal surgery (HR 0.361, p=0.042) and any disease complication (HR 0.567, p=0.006). |
| Panaccione et al (2017)53 | RCT | Treat-to-target approach versus conventional step-up care | 0.95±1.9 years | CDEIS<4 and absence of deep ulcers | T2T approach more effective in achieving mucosal healing (45.9% vs 30.3, p<0.01), deep remission (36.9 vs 23.0, p=0.014), biological remission (29.5% vs 15.6%, p=0.006) and endoscopic remission (45.9% vs 30.3%, p=0.01), whereas no differences found for CDEIS=0 (18.0% vs 16.4%, p=0.72) |
| Kwak et al (2014)39 | Retrospective cohort | Early immunomodulator use versus conventional therapy | 6 months in the ET group | Clinical remission | Clinical remission and corticosteroid-free remission rates higher in the ET group (p=0.043 and p=0.035). Adverse events also more frequent in the ET group (p=0.029) |
| Kim et al (2016)41 | Retrospective study | Early immunomodulator use versus conventional therapy | 6 months in the ET group | Need for surgery | ET was associated with lower risk of surgery (p=0.017) and delayed onset of complications (p=0.050) |
| Nuij et al (2015)40 | Retrospective cohort | Early anti-TNF versus conventional step-up approach | ≤16 months | IBD-related complications | No differences in terms of IBD-related complications and rates of mucosal healing between the two groups |
anti-TNF, antitumour necrosis factor α; CD, Crohn’s disease; CDEIS, Crohn’s Disease Endoscopic Index of Severity; CR, clinical remission; CRP, C-reactive protein; ET, early treatment; IBD, inflammatory bowel disease; IM, immunomodulator; MH, mucosal healing; NA, not applicable/not available; RCT, randomised controlled trial; T2T, treat to target; TD, top down.