Randomised, double-blind, controlled trials assessing medical treatments preventing postoperative recurrence.
| Publication: first author and date . | Treatments evaluated . | Number of patients in each group . | Primary endpoint . | Secondary endpoints . | Primary endpoint result . |
|---|---|---|---|---|---|
| de Bruyn 2020 | Oral vitamin D vs placebo | 72 vs 71 | Endoscopic recurrence [ER]: Rutgeerts Score [RS] >i2a at M6 | Clinical recurrence [CR]: CDAI >220, quality of life [IBDQ, SF36, EQ5D] Subgroups analysis depending on baseline Vitamin D levels | 58% vs 66% p = 0.37 |
| Bommelaer 2020. | Curcumin vs placebo | 31 vs 31 | ER: RS >i1 at M6 | ER: RS >i2 CR: CDAI >150, quality of life, adverse events | 58% vs 68% p = 0.60 |
| Fukushima 2018 | Infliximab vs no infliximab | 19 vs 19 | ER: RS >i2 at M24 and/or CR: CDAI >150 at M24 | CR: CDAI at M6, M12, M18 and M24 ER: M12 | 52.6% vs 94.7% p <0.01 |
| Vera-Mendoza 2017 | Adalimumab vs azathioprine | 45 vs 39 | ER: RS >i2a at M12 | CR: CDAI >200 BR: CRP, calprotectin at M6 and M12 IR: MRI at M12 Others: hospitalisations, adverse events at M12 | 42.2% vs 59% p = 0.12 |
| Mowat 2016 | Mercaptopurine vs placebo | 128 vs 112 | CR: CDAI >150 + increase of 100 points AND need for anti-inflammatory rescue therapy or surgery [survival analysis during 3 years] | ER: RS >i1 CR SR Others: need for AI therapy, QoL [IBDQ], adverse events | Median follow-up: 13% vs 23% p = 0.07 |
| Regueiro 2016 | Infliximab vs placebo | 147 vs 150 | ER: RS >i1 AND CR: CDAI >200 + increase of 70 points OR complication OR new specific treatment OR surgical recurrence [SR] at M18 or before | ER: at M18 or before CR: at M24 or before | 12.9% vs 20% p = 0.10 |
| Ferrante 2015 | Systematic azathioprine vs endoscopy-driven azathioprine [RS >i1] at M6 | 32 vs 31 | ER: RS >i1 at M24 | ER: RS >i0 at M24 CR: CDAI <150 at M24 | 50% vs 58% p = 0.52 |
| Zhu 2015 | Trypterygium wilfoordi hook vs azathioprine | 45 vs 45 | CR: symptoms AND endoscopic lesions AND new medical treatment or surgery at W26 and 52 | ER: RS >i1 at M6 and M12 BR: CRP Other: IBDQ, safety | 26% vs 18% p = 0.45 |
| De Cruz 2015 | Adalimumab vs thiopurines in high-risk patients | 28 vs 73 | ER: RS >i1 at M18 | CR: CDAI >150 or 200 BR: CRP SR Mucosal recurrence | 21% vs 45% p = 0.03 |
| Tursi 2014 | Adalimumab vs infliximab | 10 vs 10 | ER: RS >i1 at M12 CR: HBI >7 at M12 Other: histology: Geboes score at M12 | BR: CRP | 20% vs 10% [ER] p = 1 |
| Ren 2013 | Trypterygium wilfoordi vs mesalazine | 21 vs 18 | CR: ER + CDAI >150 or CD symptoms + treatment change or surgery | ER: RS >i1 at M12 CR: Change in the CDAI BR: CRP | 19% vs 50% p = <0.01 |
| Armuzzi 2013 | Azathioprine vs infliximab | 11 vs 11 | ER: RS > i1 at M12 CR: HBI >7 at M12 Histology score by Regueiro et al. [2009] at M12 | BR: CRP | 40% vs 9% [ER] p = 0.14 |
| Herfarth 2013 | Ciprofloxacin vs placebo | 17 vs 16 | ER: RS >i1 or Marteau score >c2 at M12 | CR: HBI >5 or elevation 3 points Others: adverse events | 65% vs 69% p = 0.81 |
| Manosa 2013 | Azathioprine + metronidazole vs placebo | 25 vs 25 | ER: RS >i1 at M6 | ER: RS >i2 at M6 CR: HBI >7 + endoscopic or radiological lesions | 28% vs 44% p = 0.19 |
| Savarino 2013 | Mesalazine vs azathioprine vs adalimumab | 18 vs 17 vs 16 | ER: RS >i1 at M24 CR: if Hanauer score [2004] >1 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Radiological recurrence if Hanauer score >1 IBDQ | 83.3% vs 64.7% vs 6.3% p = 0.01 |
| Yoshida 2012 | Infliximab vs no infliximab | 15 vs 16 | CR: CDAI <150, IOIBD <2 and CRP <0.3 at M12 and M36 | ER: RS >i1 at M12 and M36 | 100% and 93.3% vs 68.8% and 56.3% p <0.03 |
| Reinisch 2010 | Azathioprine vs mesalazine | 41 vs 37 | Therapeutic failure at M12 CDAI >200 and increase of >60 points, study drug discontinuation due to lack of efficacy or intolerable AE | ER: endoscopic improvement at M12 [all patients had endoscopic recurrence at M6] improvement of 1 point at least BR: CRP CR: CDAI change, IBDQ Others: adverse events | 22% vs 11.1% p = 0.19 |
| Regueiro 2009 | Infliximab vs placebo | 11 vs 13 | ER: RS >i1 at M12 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Histology score modified from D’Haens and et al. [1998] | 9.1% vs 84.6% p <0.01 |
| D’Haens 2008 | Metronidazole/placebo vs metronidazole/azathioprine | 29 vs 32 | ER: RS >i1 at M3 and M12 | CR: CDAI >250 Adverse events | 78% vs 55% p = 0.04 |
| Van Gossum 2007 | Lactobacillus johnsonii la1 vs placebo | 34 vs 36 | ER: >i1 at M3 | CR: [CDAI] 150 with an increase of 70 points or higher from baseline] at 12 weeks Histological score at 12 weeks or on relapse BR: CRP levels at 12 weeks or on relapse | Mean endoscopic score not different |
| Marteau 2006 | Lactobacillus johnsonii la1 vs placebo | 48 vs 50 | ER: RS >i1 or Marteau score >c2 at M6 | ER: RS >i2 at M6 CR: CDAI >200 | 49% vs 64% p = 0.15 |
| Rutgeerts 2005 | Ornidazole vs placebo | 38 vs 40 | CR: CD symptoms and CDAI >250 OR surgery/CD related therapy introduced at M12 | ER: RS >i1 at M3 and M12 CR: at M24 and 36 IR: barium meal radiograph W12 Histological recurrence [specific items] | 7.9% vs 37.5% p <0.01 |
| Hanauer 2004 | 6-mercaptopurine vs mesalamine vs placebo | 47 vs 44 vs 40 | CR: Score >1 ['moderate symptoms'] at M24 Imaging recurrence [IR]: Score >1 ['linear ulcers'] at M24 ER: RS >i1 at M24 | Others: AE | 50% vs 58% vs 77% p <0.05 |
| Ardizzone 2004 | Azathioprine vs mesalamine | 70 vs 70 | CR: CDAI >200 [CD symptoms] at M24 +/- radiological/endoscopic and laboratory findings SR: subsequent surgical procedure | Others: AE | 17% vs 28% [CR] p = 0.20 6% vs 10% p = 0.50 |
| Caprilli 2003 | Mesalamine 4g/day vs mesalamine 2.4g/day | 101 vs 105 | ER: RS >i0, i1 or i2 at M12 | CR: CDAI >150 and increase of 100 points at M12 | ER i0: 46% vs 62% p = 0.04 No difference other endoscopic endpoints |
| Prantera 2002 | Lactobacillus gg vs placebo | 23 vs 22 | ER: RS >i1 or i2 at M12 | CR: CDAI >150 and endoscopic lesions at M12 | 60% vs 35.3% p = 0.30 |
| Colombel 2001 | Tenovil 4 μg/kg once daily [QD] vs 8 μg/kg twice weekly [TIW] vs placebo [QD or TIW] | 22 vs 21 vs 22 | ER: RS >i0 at M3 | CR: symptoms leading to therapeutic adjustment Histological recurrence Adverse events | 52% vs 46% p NS |
| Lochs 2000 | Mesalamine vs placebo | 154 vs 170 | CR: CDAI >250 OR CDAI >200 with increase of 60 points OR subsequent surgery OR complication [fistula, stenosis] at M18 | ER: RS >i1 at M12 | 24.5% vs 31.4% p = 0.10 |
| Hellers 1999 | Budesonide vs placebo | 63 vs 66 | ER: RS >i1 at M3 and M12 | CR: CDAI SR Complications | 21% vs 47% [M3] p = 0.11 and 32% vs 65% [M12] p = 0.05 |
| Ewe 1999 | Budesonide vs placebo | 43 vs 40 | ER: RS >i1 at M3 and M12, CR: CDAI >200 OR increase of 60 points if colonoscopy refused | CR: CDAI, global wellbeing Histology | 57% vs 70% p NS |
| Florent 1996 | Mesalazine vs placebo | 65 vs 61 | ER: RS >i1 at M3 | 50% vs 63% p = 0.16 | |
| McLeod 1995 | Mesalamine vs placebo | 87 vs 76 | CR: CD symptoms [necessitating treatment] AND radiological/endoscopic lesions | ER IR: radiological recurrence: 'lesions' | 31% vs 41% p = 0.03 |
| Brignola 1995 | Mesalamine vs placebo | 44 vs 43 | ER: RS >i2 at M12 CR: CDAI >150 and increase of 100 points | Laboratory tests | 24% vs 56% p <0.004 |
| Rutgeerts 1995 | Metronidazole vs placebo | 30 vs 30 | ER: RS >i2 [severe] at M3 and M36 and lesions in the neoterminal ileum | CR: at M12, M24 and M36: CD symptoms necessitating treatment | 52% vs 73% [lesions neoterminal ileum] p = 0.09 13% vs 43% [severe] p = 0.02 |
| Caprilli 1994 | Mesalazine vs no treatment | ER: RS >i0 and i1 at M6 and M12 and M24 CR: CDAI >150 and increase of 100 points | 52% vs 85% [M24] p <0.01 18% vs 41% [CR] p <0.01 |
| Publication: first author and date . | Treatments evaluated . | Number of patients in each group . | Primary endpoint . | Secondary endpoints . | Primary endpoint result . |
|---|---|---|---|---|---|
| de Bruyn 2020 | Oral vitamin D vs placebo | 72 vs 71 | Endoscopic recurrence [ER]: Rutgeerts Score [RS] >i2a at M6 | Clinical recurrence [CR]: CDAI >220, quality of life [IBDQ, SF36, EQ5D] Subgroups analysis depending on baseline Vitamin D levels | 58% vs 66% p = 0.37 |
| Bommelaer 2020. | Curcumin vs placebo | 31 vs 31 | ER: RS >i1 at M6 | ER: RS >i2 CR: CDAI >150, quality of life, adverse events | 58% vs 68% p = 0.60 |
| Fukushima 2018 | Infliximab vs no infliximab | 19 vs 19 | ER: RS >i2 at M24 and/or CR: CDAI >150 at M24 | CR: CDAI at M6, M12, M18 and M24 ER: M12 | 52.6% vs 94.7% p <0.01 |
| Vera-Mendoza 2017 | Adalimumab vs azathioprine | 45 vs 39 | ER: RS >i2a at M12 | CR: CDAI >200 BR: CRP, calprotectin at M6 and M12 IR: MRI at M12 Others: hospitalisations, adverse events at M12 | 42.2% vs 59% p = 0.12 |
| Mowat 2016 | Mercaptopurine vs placebo | 128 vs 112 | CR: CDAI >150 + increase of 100 points AND need for anti-inflammatory rescue therapy or surgery [survival analysis during 3 years] | ER: RS >i1 CR SR Others: need for AI therapy, QoL [IBDQ], adverse events | Median follow-up: 13% vs 23% p = 0.07 |
| Regueiro 2016 | Infliximab vs placebo | 147 vs 150 | ER: RS >i1 AND CR: CDAI >200 + increase of 70 points OR complication OR new specific treatment OR surgical recurrence [SR] at M18 or before | ER: at M18 or before CR: at M24 or before | 12.9% vs 20% p = 0.10 |
| Ferrante 2015 | Systematic azathioprine vs endoscopy-driven azathioprine [RS >i1] at M6 | 32 vs 31 | ER: RS >i1 at M24 | ER: RS >i0 at M24 CR: CDAI <150 at M24 | 50% vs 58% p = 0.52 |
| Zhu 2015 | Trypterygium wilfoordi hook vs azathioprine | 45 vs 45 | CR: symptoms AND endoscopic lesions AND new medical treatment or surgery at W26 and 52 | ER: RS >i1 at M6 and M12 BR: CRP Other: IBDQ, safety | 26% vs 18% p = 0.45 |
| De Cruz 2015 | Adalimumab vs thiopurines in high-risk patients | 28 vs 73 | ER: RS >i1 at M18 | CR: CDAI >150 or 200 BR: CRP SR Mucosal recurrence | 21% vs 45% p = 0.03 |
| Tursi 2014 | Adalimumab vs infliximab | 10 vs 10 | ER: RS >i1 at M12 CR: HBI >7 at M12 Other: histology: Geboes score at M12 | BR: CRP | 20% vs 10% [ER] p = 1 |
| Ren 2013 | Trypterygium wilfoordi vs mesalazine | 21 vs 18 | CR: ER + CDAI >150 or CD symptoms + treatment change or surgery | ER: RS >i1 at M12 CR: Change in the CDAI BR: CRP | 19% vs 50% p = <0.01 |
| Armuzzi 2013 | Azathioprine vs infliximab | 11 vs 11 | ER: RS > i1 at M12 CR: HBI >7 at M12 Histology score by Regueiro et al. [2009] at M12 | BR: CRP | 40% vs 9% [ER] p = 0.14 |
| Herfarth 2013 | Ciprofloxacin vs placebo | 17 vs 16 | ER: RS >i1 or Marteau score >c2 at M12 | CR: HBI >5 or elevation 3 points Others: adverse events | 65% vs 69% p = 0.81 |
| Manosa 2013 | Azathioprine + metronidazole vs placebo | 25 vs 25 | ER: RS >i1 at M6 | ER: RS >i2 at M6 CR: HBI >7 + endoscopic or radiological lesions | 28% vs 44% p = 0.19 |
| Savarino 2013 | Mesalazine vs azathioprine vs adalimumab | 18 vs 17 vs 16 | ER: RS >i1 at M24 CR: if Hanauer score [2004] >1 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Radiological recurrence if Hanauer score >1 IBDQ | 83.3% vs 64.7% vs 6.3% p = 0.01 |
| Yoshida 2012 | Infliximab vs no infliximab | 15 vs 16 | CR: CDAI <150, IOIBD <2 and CRP <0.3 at M12 and M36 | ER: RS >i1 at M12 and M36 | 100% and 93.3% vs 68.8% and 56.3% p <0.03 |
| Reinisch 2010 | Azathioprine vs mesalazine | 41 vs 37 | Therapeutic failure at M12 CDAI >200 and increase of >60 points, study drug discontinuation due to lack of efficacy or intolerable AE | ER: endoscopic improvement at M12 [all patients had endoscopic recurrence at M6] improvement of 1 point at least BR: CRP CR: CDAI change, IBDQ Others: adverse events | 22% vs 11.1% p = 0.19 |
| Regueiro 2009 | Infliximab vs placebo | 11 vs 13 | ER: RS >i1 at M12 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Histology score modified from D’Haens and et al. [1998] | 9.1% vs 84.6% p <0.01 |
| D’Haens 2008 | Metronidazole/placebo vs metronidazole/azathioprine | 29 vs 32 | ER: RS >i1 at M3 and M12 | CR: CDAI >250 Adverse events | 78% vs 55% p = 0.04 |
| Van Gossum 2007 | Lactobacillus johnsonii la1 vs placebo | 34 vs 36 | ER: >i1 at M3 | CR: [CDAI] 150 with an increase of 70 points or higher from baseline] at 12 weeks Histological score at 12 weeks or on relapse BR: CRP levels at 12 weeks or on relapse | Mean endoscopic score not different |
| Marteau 2006 | Lactobacillus johnsonii la1 vs placebo | 48 vs 50 | ER: RS >i1 or Marteau score >c2 at M6 | ER: RS >i2 at M6 CR: CDAI >200 | 49% vs 64% p = 0.15 |
| Rutgeerts 2005 | Ornidazole vs placebo | 38 vs 40 | CR: CD symptoms and CDAI >250 OR surgery/CD related therapy introduced at M12 | ER: RS >i1 at M3 and M12 CR: at M24 and 36 IR: barium meal radiograph W12 Histological recurrence [specific items] | 7.9% vs 37.5% p <0.01 |
| Hanauer 2004 | 6-mercaptopurine vs mesalamine vs placebo | 47 vs 44 vs 40 | CR: Score >1 ['moderate symptoms'] at M24 Imaging recurrence [IR]: Score >1 ['linear ulcers'] at M24 ER: RS >i1 at M24 | Others: AE | 50% vs 58% vs 77% p <0.05 |
| Ardizzone 2004 | Azathioprine vs mesalamine | 70 vs 70 | CR: CDAI >200 [CD symptoms] at M24 +/- radiological/endoscopic and laboratory findings SR: subsequent surgical procedure | Others: AE | 17% vs 28% [CR] p = 0.20 6% vs 10% p = 0.50 |
| Caprilli 2003 | Mesalamine 4g/day vs mesalamine 2.4g/day | 101 vs 105 | ER: RS >i0, i1 or i2 at M12 | CR: CDAI >150 and increase of 100 points at M12 | ER i0: 46% vs 62% p = 0.04 No difference other endoscopic endpoints |
| Prantera 2002 | Lactobacillus gg vs placebo | 23 vs 22 | ER: RS >i1 or i2 at M12 | CR: CDAI >150 and endoscopic lesions at M12 | 60% vs 35.3% p = 0.30 |
| Colombel 2001 | Tenovil 4 μg/kg once daily [QD] vs 8 μg/kg twice weekly [TIW] vs placebo [QD or TIW] | 22 vs 21 vs 22 | ER: RS >i0 at M3 | CR: symptoms leading to therapeutic adjustment Histological recurrence Adverse events | 52% vs 46% p NS |
| Lochs 2000 | Mesalamine vs placebo | 154 vs 170 | CR: CDAI >250 OR CDAI >200 with increase of 60 points OR subsequent surgery OR complication [fistula, stenosis] at M18 | ER: RS >i1 at M12 | 24.5% vs 31.4% p = 0.10 |
| Hellers 1999 | Budesonide vs placebo | 63 vs 66 | ER: RS >i1 at M3 and M12 | CR: CDAI SR Complications | 21% vs 47% [M3] p = 0.11 and 32% vs 65% [M12] p = 0.05 |
| Ewe 1999 | Budesonide vs placebo | 43 vs 40 | ER: RS >i1 at M3 and M12, CR: CDAI >200 OR increase of 60 points if colonoscopy refused | CR: CDAI, global wellbeing Histology | 57% vs 70% p NS |
| Florent 1996 | Mesalazine vs placebo | 65 vs 61 | ER: RS >i1 at M3 | 50% vs 63% p = 0.16 | |
| McLeod 1995 | Mesalamine vs placebo | 87 vs 76 | CR: CD symptoms [necessitating treatment] AND radiological/endoscopic lesions | ER IR: radiological recurrence: 'lesions' | 31% vs 41% p = 0.03 |
| Brignola 1995 | Mesalamine vs placebo | 44 vs 43 | ER: RS >i2 at M12 CR: CDAI >150 and increase of 100 points | Laboratory tests | 24% vs 56% p <0.004 |
| Rutgeerts 1995 | Metronidazole vs placebo | 30 vs 30 | ER: RS >i2 [severe] at M3 and M36 and lesions in the neoterminal ileum | CR: at M12, M24 and M36: CD symptoms necessitating treatment | 52% vs 73% [lesions neoterminal ileum] p = 0.09 13% vs 43% [severe] p = 0.02 |
| Caprilli 1994 | Mesalazine vs no treatment | ER: RS >i0 and i1 at M6 and M12 and M24 CR: CDAI >150 and increase of 100 points | 52% vs 85% [M24] p <0.01 18% vs 41% [CR] p <0.01 |
ER: endoscopic recurrence; RS: Rutgeerts score; CR: clinical recurrence; CDAI: Crohn’s disease activity index; IR: imaging recurrence; CRP: C reactive protein; BR: biological recurrence.
Randomised, double-blind, controlled trials assessing medical treatments preventing postoperative recurrence.
| Publication: first author and date . | Treatments evaluated . | Number of patients in each group . | Primary endpoint . | Secondary endpoints . | Primary endpoint result . |
|---|---|---|---|---|---|
| de Bruyn 2020 | Oral vitamin D vs placebo | 72 vs 71 | Endoscopic recurrence [ER]: Rutgeerts Score [RS] >i2a at M6 | Clinical recurrence [CR]: CDAI >220, quality of life [IBDQ, SF36, EQ5D] Subgroups analysis depending on baseline Vitamin D levels | 58% vs 66% p = 0.37 |
| Bommelaer 2020. | Curcumin vs placebo | 31 vs 31 | ER: RS >i1 at M6 | ER: RS >i2 CR: CDAI >150, quality of life, adverse events | 58% vs 68% p = 0.60 |
| Fukushima 2018 | Infliximab vs no infliximab | 19 vs 19 | ER: RS >i2 at M24 and/or CR: CDAI >150 at M24 | CR: CDAI at M6, M12, M18 and M24 ER: M12 | 52.6% vs 94.7% p <0.01 |
| Vera-Mendoza 2017 | Adalimumab vs azathioprine | 45 vs 39 | ER: RS >i2a at M12 | CR: CDAI >200 BR: CRP, calprotectin at M6 and M12 IR: MRI at M12 Others: hospitalisations, adverse events at M12 | 42.2% vs 59% p = 0.12 |
| Mowat 2016 | Mercaptopurine vs placebo | 128 vs 112 | CR: CDAI >150 + increase of 100 points AND need for anti-inflammatory rescue therapy or surgery [survival analysis during 3 years] | ER: RS >i1 CR SR Others: need for AI therapy, QoL [IBDQ], adverse events | Median follow-up: 13% vs 23% p = 0.07 |
| Regueiro 2016 | Infliximab vs placebo | 147 vs 150 | ER: RS >i1 AND CR: CDAI >200 + increase of 70 points OR complication OR new specific treatment OR surgical recurrence [SR] at M18 or before | ER: at M18 or before CR: at M24 or before | 12.9% vs 20% p = 0.10 |
| Ferrante 2015 | Systematic azathioprine vs endoscopy-driven azathioprine [RS >i1] at M6 | 32 vs 31 | ER: RS >i1 at M24 | ER: RS >i0 at M24 CR: CDAI <150 at M24 | 50% vs 58% p = 0.52 |
| Zhu 2015 | Trypterygium wilfoordi hook vs azathioprine | 45 vs 45 | CR: symptoms AND endoscopic lesions AND new medical treatment or surgery at W26 and 52 | ER: RS >i1 at M6 and M12 BR: CRP Other: IBDQ, safety | 26% vs 18% p = 0.45 |
| De Cruz 2015 | Adalimumab vs thiopurines in high-risk patients | 28 vs 73 | ER: RS >i1 at M18 | CR: CDAI >150 or 200 BR: CRP SR Mucosal recurrence | 21% vs 45% p = 0.03 |
| Tursi 2014 | Adalimumab vs infliximab | 10 vs 10 | ER: RS >i1 at M12 CR: HBI >7 at M12 Other: histology: Geboes score at M12 | BR: CRP | 20% vs 10% [ER] p = 1 |
| Ren 2013 | Trypterygium wilfoordi vs mesalazine | 21 vs 18 | CR: ER + CDAI >150 or CD symptoms + treatment change or surgery | ER: RS >i1 at M12 CR: Change in the CDAI BR: CRP | 19% vs 50% p = <0.01 |
| Armuzzi 2013 | Azathioprine vs infliximab | 11 vs 11 | ER: RS > i1 at M12 CR: HBI >7 at M12 Histology score by Regueiro et al. [2009] at M12 | BR: CRP | 40% vs 9% [ER] p = 0.14 |
| Herfarth 2013 | Ciprofloxacin vs placebo | 17 vs 16 | ER: RS >i1 or Marteau score >c2 at M12 | CR: HBI >5 or elevation 3 points Others: adverse events | 65% vs 69% p = 0.81 |
| Manosa 2013 | Azathioprine + metronidazole vs placebo | 25 vs 25 | ER: RS >i1 at M6 | ER: RS >i2 at M6 CR: HBI >7 + endoscopic or radiological lesions | 28% vs 44% p = 0.19 |
| Savarino 2013 | Mesalazine vs azathioprine vs adalimumab | 18 vs 17 vs 16 | ER: RS >i1 at M24 CR: if Hanauer score [2004] >1 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Radiological recurrence if Hanauer score >1 IBDQ | 83.3% vs 64.7% vs 6.3% p = 0.01 |
| Yoshida 2012 | Infliximab vs no infliximab | 15 vs 16 | CR: CDAI <150, IOIBD <2 and CRP <0.3 at M12 and M36 | ER: RS >i1 at M12 and M36 | 100% and 93.3% vs 68.8% and 56.3% p <0.03 |
| Reinisch 2010 | Azathioprine vs mesalazine | 41 vs 37 | Therapeutic failure at M12 CDAI >200 and increase of >60 points, study drug discontinuation due to lack of efficacy or intolerable AE | ER: endoscopic improvement at M12 [all patients had endoscopic recurrence at M6] improvement of 1 point at least BR: CRP CR: CDAI change, IBDQ Others: adverse events | 22% vs 11.1% p = 0.19 |
| Regueiro 2009 | Infliximab vs placebo | 11 vs 13 | ER: RS >i1 at M12 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Histology score modified from D’Haens and et al. [1998] | 9.1% vs 84.6% p <0.01 |
| D’Haens 2008 | Metronidazole/placebo vs metronidazole/azathioprine | 29 vs 32 | ER: RS >i1 at M3 and M12 | CR: CDAI >250 Adverse events | 78% vs 55% p = 0.04 |
| Van Gossum 2007 | Lactobacillus johnsonii la1 vs placebo | 34 vs 36 | ER: >i1 at M3 | CR: [CDAI] 150 with an increase of 70 points or higher from baseline] at 12 weeks Histological score at 12 weeks or on relapse BR: CRP levels at 12 weeks or on relapse | Mean endoscopic score not different |
| Marteau 2006 | Lactobacillus johnsonii la1 vs placebo | 48 vs 50 | ER: RS >i1 or Marteau score >c2 at M6 | ER: RS >i2 at M6 CR: CDAI >200 | 49% vs 64% p = 0.15 |
| Rutgeerts 2005 | Ornidazole vs placebo | 38 vs 40 | CR: CD symptoms and CDAI >250 OR surgery/CD related therapy introduced at M12 | ER: RS >i1 at M3 and M12 CR: at M24 and 36 IR: barium meal radiograph W12 Histological recurrence [specific items] | 7.9% vs 37.5% p <0.01 |
| Hanauer 2004 | 6-mercaptopurine vs mesalamine vs placebo | 47 vs 44 vs 40 | CR: Score >1 ['moderate symptoms'] at M24 Imaging recurrence [IR]: Score >1 ['linear ulcers'] at M24 ER: RS >i1 at M24 | Others: AE | 50% vs 58% vs 77% p <0.05 |
| Ardizzone 2004 | Azathioprine vs mesalamine | 70 vs 70 | CR: CDAI >200 [CD symptoms] at M24 +/- radiological/endoscopic and laboratory findings SR: subsequent surgical procedure | Others: AE | 17% vs 28% [CR] p = 0.20 6% vs 10% p = 0.50 |
| Caprilli 2003 | Mesalamine 4g/day vs mesalamine 2.4g/day | 101 vs 105 | ER: RS >i0, i1 or i2 at M12 | CR: CDAI >150 and increase of 100 points at M12 | ER i0: 46% vs 62% p = 0.04 No difference other endoscopic endpoints |
| Prantera 2002 | Lactobacillus gg vs placebo | 23 vs 22 | ER: RS >i1 or i2 at M12 | CR: CDAI >150 and endoscopic lesions at M12 | 60% vs 35.3% p = 0.30 |
| Colombel 2001 | Tenovil 4 μg/kg once daily [QD] vs 8 μg/kg twice weekly [TIW] vs placebo [QD or TIW] | 22 vs 21 vs 22 | ER: RS >i0 at M3 | CR: symptoms leading to therapeutic adjustment Histological recurrence Adverse events | 52% vs 46% p NS |
| Lochs 2000 | Mesalamine vs placebo | 154 vs 170 | CR: CDAI >250 OR CDAI >200 with increase of 60 points OR subsequent surgery OR complication [fistula, stenosis] at M18 | ER: RS >i1 at M12 | 24.5% vs 31.4% p = 0.10 |
| Hellers 1999 | Budesonide vs placebo | 63 vs 66 | ER: RS >i1 at M3 and M12 | CR: CDAI SR Complications | 21% vs 47% [M3] p = 0.11 and 32% vs 65% [M12] p = 0.05 |
| Ewe 1999 | Budesonide vs placebo | 43 vs 40 | ER: RS >i1 at M3 and M12, CR: CDAI >200 OR increase of 60 points if colonoscopy refused | CR: CDAI, global wellbeing Histology | 57% vs 70% p NS |
| Florent 1996 | Mesalazine vs placebo | 65 vs 61 | ER: RS >i1 at M3 | 50% vs 63% p = 0.16 | |
| McLeod 1995 | Mesalamine vs placebo | 87 vs 76 | CR: CD symptoms [necessitating treatment] AND radiological/endoscopic lesions | ER IR: radiological recurrence: 'lesions' | 31% vs 41% p = 0.03 |
| Brignola 1995 | Mesalamine vs placebo | 44 vs 43 | ER: RS >i2 at M12 CR: CDAI >150 and increase of 100 points | Laboratory tests | 24% vs 56% p <0.004 |
| Rutgeerts 1995 | Metronidazole vs placebo | 30 vs 30 | ER: RS >i2 [severe] at M3 and M36 and lesions in the neoterminal ileum | CR: at M12, M24 and M36: CD symptoms necessitating treatment | 52% vs 73% [lesions neoterminal ileum] p = 0.09 13% vs 43% [severe] p = 0.02 |
| Caprilli 1994 | Mesalazine vs no treatment | ER: RS >i0 and i1 at M6 and M12 and M24 CR: CDAI >150 and increase of 100 points | 52% vs 85% [M24] p <0.01 18% vs 41% [CR] p <0.01 |
| Publication: first author and date . | Treatments evaluated . | Number of patients in each group . | Primary endpoint . | Secondary endpoints . | Primary endpoint result . |
|---|---|---|---|---|---|
| de Bruyn 2020 | Oral vitamin D vs placebo | 72 vs 71 | Endoscopic recurrence [ER]: Rutgeerts Score [RS] >i2a at M6 | Clinical recurrence [CR]: CDAI >220, quality of life [IBDQ, SF36, EQ5D] Subgroups analysis depending on baseline Vitamin D levels | 58% vs 66% p = 0.37 |
| Bommelaer 2020. | Curcumin vs placebo | 31 vs 31 | ER: RS >i1 at M6 | ER: RS >i2 CR: CDAI >150, quality of life, adverse events | 58% vs 68% p = 0.60 |
| Fukushima 2018 | Infliximab vs no infliximab | 19 vs 19 | ER: RS >i2 at M24 and/or CR: CDAI >150 at M24 | CR: CDAI at M6, M12, M18 and M24 ER: M12 | 52.6% vs 94.7% p <0.01 |
| Vera-Mendoza 2017 | Adalimumab vs azathioprine | 45 vs 39 | ER: RS >i2a at M12 | CR: CDAI >200 BR: CRP, calprotectin at M6 and M12 IR: MRI at M12 Others: hospitalisations, adverse events at M12 | 42.2% vs 59% p = 0.12 |
| Mowat 2016 | Mercaptopurine vs placebo | 128 vs 112 | CR: CDAI >150 + increase of 100 points AND need for anti-inflammatory rescue therapy or surgery [survival analysis during 3 years] | ER: RS >i1 CR SR Others: need for AI therapy, QoL [IBDQ], adverse events | Median follow-up: 13% vs 23% p = 0.07 |
| Regueiro 2016 | Infliximab vs placebo | 147 vs 150 | ER: RS >i1 AND CR: CDAI >200 + increase of 70 points OR complication OR new specific treatment OR surgical recurrence [SR] at M18 or before | ER: at M18 or before CR: at M24 or before | 12.9% vs 20% p = 0.10 |
| Ferrante 2015 | Systematic azathioprine vs endoscopy-driven azathioprine [RS >i1] at M6 | 32 vs 31 | ER: RS >i1 at M24 | ER: RS >i0 at M24 CR: CDAI <150 at M24 | 50% vs 58% p = 0.52 |
| Zhu 2015 | Trypterygium wilfoordi hook vs azathioprine | 45 vs 45 | CR: symptoms AND endoscopic lesions AND new medical treatment or surgery at W26 and 52 | ER: RS >i1 at M6 and M12 BR: CRP Other: IBDQ, safety | 26% vs 18% p = 0.45 |
| De Cruz 2015 | Adalimumab vs thiopurines in high-risk patients | 28 vs 73 | ER: RS >i1 at M18 | CR: CDAI >150 or 200 BR: CRP SR Mucosal recurrence | 21% vs 45% p = 0.03 |
| Tursi 2014 | Adalimumab vs infliximab | 10 vs 10 | ER: RS >i1 at M12 CR: HBI >7 at M12 Other: histology: Geboes score at M12 | BR: CRP | 20% vs 10% [ER] p = 1 |
| Ren 2013 | Trypterygium wilfoordi vs mesalazine | 21 vs 18 | CR: ER + CDAI >150 or CD symptoms + treatment change or surgery | ER: RS >i1 at M12 CR: Change in the CDAI BR: CRP | 19% vs 50% p = <0.01 |
| Armuzzi 2013 | Azathioprine vs infliximab | 11 vs 11 | ER: RS > i1 at M12 CR: HBI >7 at M12 Histology score by Regueiro et al. [2009] at M12 | BR: CRP | 40% vs 9% [ER] p = 0.14 |
| Herfarth 2013 | Ciprofloxacin vs placebo | 17 vs 16 | ER: RS >i1 or Marteau score >c2 at M12 | CR: HBI >5 or elevation 3 points Others: adverse events | 65% vs 69% p = 0.81 |
| Manosa 2013 | Azathioprine + metronidazole vs placebo | 25 vs 25 | ER: RS >i1 at M6 | ER: RS >i2 at M6 CR: HBI >7 + endoscopic or radiological lesions | 28% vs 44% p = 0.19 |
| Savarino 2013 | Mesalazine vs azathioprine vs adalimumab | 18 vs 17 vs 16 | ER: RS >i1 at M24 CR: if Hanauer score [2004] >1 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Radiological recurrence if Hanauer score >1 IBDQ | 83.3% vs 64.7% vs 6.3% p = 0.01 |
| Yoshida 2012 | Infliximab vs no infliximab | 15 vs 16 | CR: CDAI <150, IOIBD <2 and CRP <0.3 at M12 and M36 | ER: RS >i1 at M12 and M36 | 100% and 93.3% vs 68.8% and 56.3% p <0.03 |
| Reinisch 2010 | Azathioprine vs mesalazine | 41 vs 37 | Therapeutic failure at M12 CDAI >200 and increase of >60 points, study drug discontinuation due to lack of efficacy or intolerable AE | ER: endoscopic improvement at M12 [all patients had endoscopic recurrence at M6] improvement of 1 point at least BR: CRP CR: CDAI change, IBDQ Others: adverse events | 22% vs 11.1% p = 0.19 |
| Regueiro 2009 | Infliximab vs placebo | 11 vs 13 | ER: RS >i1 at M12 | CR: if CDAI >150 [remission] or 200 BR: CRP, ESR Histology score modified from D’Haens and et al. [1998] | 9.1% vs 84.6% p <0.01 |
| D’Haens 2008 | Metronidazole/placebo vs metronidazole/azathioprine | 29 vs 32 | ER: RS >i1 at M3 and M12 | CR: CDAI >250 Adverse events | 78% vs 55% p = 0.04 |
| Van Gossum 2007 | Lactobacillus johnsonii la1 vs placebo | 34 vs 36 | ER: >i1 at M3 | CR: [CDAI] 150 with an increase of 70 points or higher from baseline] at 12 weeks Histological score at 12 weeks or on relapse BR: CRP levels at 12 weeks or on relapse | Mean endoscopic score not different |
| Marteau 2006 | Lactobacillus johnsonii la1 vs placebo | 48 vs 50 | ER: RS >i1 or Marteau score >c2 at M6 | ER: RS >i2 at M6 CR: CDAI >200 | 49% vs 64% p = 0.15 |
| Rutgeerts 2005 | Ornidazole vs placebo | 38 vs 40 | CR: CD symptoms and CDAI >250 OR surgery/CD related therapy introduced at M12 | ER: RS >i1 at M3 and M12 CR: at M24 and 36 IR: barium meal radiograph W12 Histological recurrence [specific items] | 7.9% vs 37.5% p <0.01 |
| Hanauer 2004 | 6-mercaptopurine vs mesalamine vs placebo | 47 vs 44 vs 40 | CR: Score >1 ['moderate symptoms'] at M24 Imaging recurrence [IR]: Score >1 ['linear ulcers'] at M24 ER: RS >i1 at M24 | Others: AE | 50% vs 58% vs 77% p <0.05 |
| Ardizzone 2004 | Azathioprine vs mesalamine | 70 vs 70 | CR: CDAI >200 [CD symptoms] at M24 +/- radiological/endoscopic and laboratory findings SR: subsequent surgical procedure | Others: AE | 17% vs 28% [CR] p = 0.20 6% vs 10% p = 0.50 |
| Caprilli 2003 | Mesalamine 4g/day vs mesalamine 2.4g/day | 101 vs 105 | ER: RS >i0, i1 or i2 at M12 | CR: CDAI >150 and increase of 100 points at M12 | ER i0: 46% vs 62% p = 0.04 No difference other endoscopic endpoints |
| Prantera 2002 | Lactobacillus gg vs placebo | 23 vs 22 | ER: RS >i1 or i2 at M12 | CR: CDAI >150 and endoscopic lesions at M12 | 60% vs 35.3% p = 0.30 |
| Colombel 2001 | Tenovil 4 μg/kg once daily [QD] vs 8 μg/kg twice weekly [TIW] vs placebo [QD or TIW] | 22 vs 21 vs 22 | ER: RS >i0 at M3 | CR: symptoms leading to therapeutic adjustment Histological recurrence Adverse events | 52% vs 46% p NS |
| Lochs 2000 | Mesalamine vs placebo | 154 vs 170 | CR: CDAI >250 OR CDAI >200 with increase of 60 points OR subsequent surgery OR complication [fistula, stenosis] at M18 | ER: RS >i1 at M12 | 24.5% vs 31.4% p = 0.10 |
| Hellers 1999 | Budesonide vs placebo | 63 vs 66 | ER: RS >i1 at M3 and M12 | CR: CDAI SR Complications | 21% vs 47% [M3] p = 0.11 and 32% vs 65% [M12] p = 0.05 |
| Ewe 1999 | Budesonide vs placebo | 43 vs 40 | ER: RS >i1 at M3 and M12, CR: CDAI >200 OR increase of 60 points if colonoscopy refused | CR: CDAI, global wellbeing Histology | 57% vs 70% p NS |
| Florent 1996 | Mesalazine vs placebo | 65 vs 61 | ER: RS >i1 at M3 | 50% vs 63% p = 0.16 | |
| McLeod 1995 | Mesalamine vs placebo | 87 vs 76 | CR: CD symptoms [necessitating treatment] AND radiological/endoscopic lesions | ER IR: radiological recurrence: 'lesions' | 31% vs 41% p = 0.03 |
| Brignola 1995 | Mesalamine vs placebo | 44 vs 43 | ER: RS >i2 at M12 CR: CDAI >150 and increase of 100 points | Laboratory tests | 24% vs 56% p <0.004 |
| Rutgeerts 1995 | Metronidazole vs placebo | 30 vs 30 | ER: RS >i2 [severe] at M3 and M36 and lesions in the neoterminal ileum | CR: at M12, M24 and M36: CD symptoms necessitating treatment | 52% vs 73% [lesions neoterminal ileum] p = 0.09 13% vs 43% [severe] p = 0.02 |
| Caprilli 1994 | Mesalazine vs no treatment | ER: RS >i0 and i1 at M6 and M12 and M24 CR: CDAI >150 and increase of 100 points | 52% vs 85% [M24] p <0.01 18% vs 41% [CR] p <0.01 |
ER: endoscopic recurrence; RS: Rutgeerts score; CR: clinical recurrence; CDAI: Crohn’s disease activity index; IR: imaging recurrence; CRP: C reactive protein; BR: biological recurrence.
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