Table 2.
Key secondary outcome measures
| Name of outcome | Specific measure to be used | Time point(s) |
| Rate of steroid-free clinical remission | PCDAI<10 (child) or CDAI<150 (adult) and off prednisone/budesonide for ≥4 weeks | Weeks 14 and 52 |
| Rate of clinical response | Decrease from baseline PCDAI of at least 12.5 points and total PCDAI<30 or a total PCDAI<10 (child)1or a reduction of CDAI>70 from baseline or CDAI<150 (adult)31 | Weeks 14 and 52 |
| Rate of primary clinical non-response | On prednisone>16 consecutive weeks from start of infliximab or a PCDAI>30 or CDAI>220 for first four infusions | Week 16 |
| Rate of primary biologic non-response | Failure to improve baseline faecal calprotectin by >100 µg/g (limited to patients with a baseline faecal calprotectin>250 µg/g) or failure to improve baseline c-reactive protein≥0.5 mg/dL (limited to patients with a baseline c-reactive protein>1.0 mg/dL) | Week 16 |
| Rate of sustained steroid-free clinical remission | PCDAI<10 (child) or CDAI<150 (adult) at dose 5 to week 52 and off prednisone/budesonide from weeks 22–52 | Weeks 22–52 |
| Rate of steroid-free clinical remission—biomarker composite | PCDAI<10 (child) or CDAI<150 (adult), off prednisone/budesonide for ≥4 weeks, CRP≤0.5 mg/dL and faecal calprotectin≤250 µg/g13 | Weeks 14 and 52 |
| Rate of endoscopic healing | SES-CD≤223 | Week 52 |
| Rate of complete endoscopic healing | SES-CD=0 | Week 52 |
| Rate of endoscopic remission | SES-CD<4 | Week 52 |
| Rate of mucosal healing | SES-CD≤2 and Ileal Global Histologic Activity Score (GHAS)/Colon Global Histologic Activity Score (CGHAS)≤2 | Week 52 |
| PK model bias | Model predicted vs actual infliximab concentration. Bias: mean predictive error (MPE) | Weeks 0–52 |
| PK model precision | Model predicted vs actual infliximab concentration. Precision: root mean squared error (RMSE) | Weeks 0–52 |
| Rate of IBD-related event—fistula | Occurrence of fistula | Weeks 0–52 |
| Rate of IBD-related hospitalisation | Occurrence of Crohn’s disease-related hospitalisation | Weeks 0–52 |
| Rate of IBD-related surgery | Occurrence of Crohn’s disease-related surgery | Weeks 0–52 |
| Rate of IBD-related intestinal stricture | Occurrence of Crohn’s disease-related intestinal stricture | Weeks 0–52 |
| Rate of IBD related—starting corticosteroids | Occurrence of patients starting a corticosteroid after week 20 | Weeks 0–52 |
| Rate of IBD-related antibodies to infliximab | Occurrence of antibodies to infliximab defined as >200 ng/mL | Weeks 0–52 |
| Rate of growth restoration—weight change | In Tanner stage I–III patients: change from baseline weight (kg) by gender and age group18 | Weeks 14–52 |
| Rate of growth restoration—height velocity | In Tanner stage I–III patients: change in height velocity (z-score) by gender18 | Weeks 14–52 |
| PK of infliximab in paediatric patients | Measured infliximab clearance at baseline and at week 52 | Weeks 0–52 |
| Correlation between infliximab induction exposure and endoscopic remission | The correlation analysis to be performed for the total area under the curve (infliximab exposure, μg*h/mL from week 0–14) and patients achieving endoscopic remission. Endoscopic remission is defined as a SES-CD≤2. | Exposure: weeks 0–14 Efficacy: week 52 |
| Correlation between infliximab induction exposure and deep remission | The correlation analysis to be performed for the total area under the curve (infliximab exposure, μg*h/mL from week 0–14) and patients in deep remission. Deep remission is defined as a PCDAI<10 (child) or CDAI<150 (adult), off prednisone/budesonide for >8 weeks and a SES-CD≤2. | Exposure: weeks 0–14 Efficacy: week 52 |
| Rate of PRO2 response | >50% improvement in total score from baseline18 | Weeks 6, 14, 26 and 52 |
| Rate of PRO2 remission | Stool frequency≤3.0 and abdominal pain≤1.0 (from baseline)32 | Weeks 6, 14, 26 and 52 |
| Quality of life and disability— IMAPCT-III score | Total IMPACT-III (child) score19 20 | Week 52 |
| Quality of life and disability—IBD disk score | Total IBD disk (without sexual function assessment) score | Week 52 |
| Quality of life and disability—short IBD score | Total Short IBD Questionnaire (adult) score | Week 52 |
| Process evaluation—usability of decision support tool | Total System Usability Scare score | Weeks 0–52 |
| Rate of adverse events | Number of adverse events | Weeks 0–52 |
| Rate of serious adverse events | Number of serious adverse events | Weeks 0–52 |
CDAI, Crohn’s disease activity index; CRP, c-reactive protein; IBD, inflammatory bowel disease; PCDAI, paediatric Crohn’s disease activity index; PK, pharmacokinetic; SES-CD, simple endoscopic score-Crohn’s disease.