eTable 4. Randomized clinical trials in children and adolescents with IBD.
| Trial | Intervention | Patient cohort | Trial design | Findings | Main ADRs |
| Griffiths A et al. 1993 (e16) |
5-ASA 50 mg/kg BW/day (max. 3 g/day) per os vs. placebo |
13 patients with active Crohn’s disease of the small intestine; age 5 to 18 years; trial period August 1988 to February 1991 |
Single-center, double-blind, placebo-controlled, crossover (2 × 8 weeks with 4-week washout phase); 20 weeks’ follow-up |
43% vs. 0% clinical response in week 8 (5-ASA vs. placebo; p = 0.130); clinical response vs. no clinical response in week 20 (5-ASA vs. placebo; p = 0.03) | Not observed |
| Levine A et al. 2003 (e22) |
Budesonide 9 mg/day per os vs. prednisone 40 mg/day per os |
33 patients with active, mild to moderate Crohn’s disease; age 8 to 18 years; trial period not stated |
Multicenter (n = 13), open-label; 12 weeks’ follow-up | 47% vs. 50% clinical remission in week 12 (budesonide vs. prednisone; not significant); 32% vs. 71% side effects (budesonide vs. prednisone; p <0.05) | 8% vs. 36% muscle involvement, 32% vs. 71% moon facies (budesonide vs. prednisone; p = 0.07 and p <0.05) |
| Escher JC et al. 2004 (e18) |
Budesonide 9 mg/day per os vs. prednisolone 1 mg/kg BW/day per os |
48 patients with active Crohn’s disease of the ileum and/or ascending colon; age 6 to 16 years; trial period April 1998 to December 2000 |
Multicenter (n = 36), double-blind; placebo-controlled; 12 weeks’ follow-up |
55% vs. 71% clinical remission in week 8 (budesonide vs. prednisolone; p = 0.25); higher morning plasma cortisol level (i.e. less adrenal suppression) in budesonide group (p = 0.003) | 50% vs. 80% glucocorticoid-associated ADRs (budesonide vs. prednisolone; p = 0.03); moon facies (23% vs. 60%; p = 0.01); acne (5% vs. 28%; p = 0.03) |
| Cezard JP et al. 2009 (e21) |
Mesalazine 50 mg/kg BW/day vs. placebo for 12 months | 122 patients with active Crohn’s disease; age <18 years; trial period 1991 to 1993 and 1996 to 1999 |
Multicenter (n = 17), double-blind, placebo-controlled; 12 months’ follow-up |
57% vs. 39% relapse after 12 months (mesalazine vs. placebo; not significant) | 1% vs. 3% adverse reactions (mesalazine vs. placebo) |
| Markowitz J et al. 2000 (e17) |
6-mercaptopurine (6-MP) 1.5 mg/kg BWday vs. placebo (plus prednisone 40 mg/day in both groups) |
55 patients with moderate to severe Crohn’s disease; age 12 to 18 years; trial period not stated |
Multicenter (n = 18), placebo-controlled, double-blind, 18 months’ follow-up |
89% clinical remission in week 48 in both groups; shorter concomitant prednisone medication in 6-MP group (p <0.001); lower cumulative prednisone dose in 6-mp group in weeks 24, 48, and 72 (p <0.01); 9% vs. 47% relapse (6-mp vs. placebo; p = 0.007) | Mild leukopenia (22%), elevated transaminases (15%) |
| Hyams J et al. 2012 (e13) |
Adalimumab 20 mg vs. 40 mg every 2 weeks subcutaneously (BW≥40 kg) or 10 mg vs. 20 mg every 2 weeks subcutaneously (BW<40 kg) |
192 patients with moderate to severe Crohn’s disease; age 6 to 17 years; trial period April 2007 to May 2010 |
Multicenter (n = 45), double-blind, open-label induction phase (4 weeks); 48 weeks’ follow-up | 28% vs. 39% clinical remission in week 26 (adalimumab 10/20 mg vs. 20/40 mg; p = 0.075) | Dose-independent: infections (55%), reaction at injection site (10%) |
| Hyams J et al. 2007 (e11) |
Infliximab 5 mg/kg BWevery 8 weeks vs. every 12 weeks intravenously | 112 patients with moderate to severe Crohn’s disease; age 6 to 17 years, trial period February 2003 to March 2004 |
Multicenter (n = 34) open-label, open-label induction phase (10 weeks); crossover (dose/interval modification); 54 weeks’ follow-up | 88% clinical response vs. 59% clinical remission in week 10; 64% vs. 33% clinical response in week 54 (infliximab every 8 vs. 12 weeks; p = 0.002); 56% vs. 24% clinical remission in week 54 (infliximab every 8 vs. 12 weeks; p <0.001) | Independent of interval: infections (56%), infusion reaction (18%) |
| Ruemmele FM et al. 2009 (e14) |
Infliximab 5 mg/kg BW every 8 weeks vs. on demand intravenously | 40 patients with acute-phase Crohn’s disease; age 7 to 17 years; trial period May 2002 to April 2005 |
Multicenter (n = 11), open-label, open-label induction phase (10 weeks); crossover (dose/interval modification); 60 weeks’ follow-up | 85% clinical remission in week 10; 83% vs. 61% clinical response in week 60 (infliximab every 8 weeks vs. on demand; p = 0.011); 23% vs. 92% relapse (infliximab every 8 weeks vs. on demand; p <0.003) | Independent of interval: infections (38%); headache, fever, skin reactions (8% each) |
| Hyams J et al. 2012 (e12) |
Infliximab 5 mg/kg BW every 8 weeks vs. every 12 weeks intravenously | 60 patients with moderate to severe ulcerative colitis; age 6 to 17 years; trial period August 2006 to June 2010 |
Multicenter (n = 23), open-label, open-label induction phase (10 weeks); 54 weeks’ follow-up | 73% clinical response in week 8; 38% vs. 18% clinical remission in week 54 (infliximab every 8 vs. 12 weeks; p = 0.146) | Independent of interval: infections (60%); infusion reaction (16%) |
| Quiros JA et al. 2009 (e15) |
5-ASA 2.25 g vs. 6.75 g/day per os | 68 patients with mild to moderate ulcerative colitis; age 5 to 17 years; trial period August 2004 to March 2006 |
Multicenter (n = 23), double-blind, 8 weeks’ follow-up | 37% vs. 45% clinical response, 9% vs. 12% clinical remission in week 8 (5-ASA 2.25 g vs. 6.75 g/day; not significant) | Dose-independent: headache (15%), abdominal pain (25%) |
| Romano C et al. 2010 (e19) |
Betamethasone dipropionate (BDP) 5 mg/day per os for 8 weeks followed by 5-ASA 80 mg/kg BW/day per os for 4 weeks vs. 5-ASA 80 mg/kg BW/day per os for 12 weeks |
30 patients with mild to moderate ulcerative colitis (pancolitis or left-sided colitis); age <18 years; trial period not stated |
Single-center, open-label; 12 months’ follow-up | 80% vs. 33% clinical remission in week 4 (BDP vs. 5-ASA; p <0.025); better clinical response in bdp group in weeks 8 (p <0.003) and 12 (p <0.015); 73% vs. 27% endoscopic remission in week 12 (bdp vs. 5-asa; p <0.025) | No significant adverse reactions reported |
| Ferry GD et al. 1993 (e20) |
Olsalazine 30 mg/kg BW/day (max. 2 g/day) per os vs. Sulfasalazine 60 mg/kg BW/day (max. 4 g/day) |
56 patients with mild to moderate ulcerative colitis; aged 2 to 17 years; trial period June 1987 to July 1989 |
Multicenter (n = 13); double-blind; 12 weeks’ follow-up | 39% vs. vs. 79% clinical remission in week 12 (olsalazine vs. sulfasalazine; p = 0.006); 36% vs. 4% failure to respond to treatment (olsalazine vs. sulfasalazine; p = 0.005) | 39% vs. 46% adverse reactions (olsalazine vs. sulfasalazine): headache, nausea, vomiting, rash, itching, diarrhea, and/or fever |
5-ASA: 5-aminosalicylates; BW: Body weight; ADR: Adverse drug reaction