Interventions for prevention of post‐operative recurrence of Crohn's disease

Glen Doherty; Gayle Bennett; Seema Patil; Adam Cheifetz; Alan C Moss

doi:10.1002/14651858.CD006873.pub2

Intervenciones para la prevención de la recurrencia posoperatoria de la enfermedad de Crohn

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Referencias

Referencias de los estudios incluidos en esta revisión

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estudios excluidos
otras referencias

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Referencias de los estudios excluidos de esta revisión

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estudios incluidos
otras referencias

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Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos

Akobeng AK, Gardener E. Oral 5‐aminosalicylic acid for maintenance of medically‐induced remission inCrohn's Disease.. Cochrane Database Syst Rev. 2005;1:CD003715.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos

Ardizzone 2004

Methods	Open label prospective randomised controlled trial
Participants	140 patients randomised following small intestinal resection or stricturoplasty
Interventions	Azathioprine 2mg/kg/day or Mesalamine 3g/day for 24 months
Outcomes	Clinical or surgical recurrence at 24 months
Notes	Jadad score 2 Inadequate description of use of placebo controls.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	High risk	Open label
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Brignola 1995

Methods	Randomised double blind placebo controlled trial
Participants	87 patients randomised following curative ileal or ileo‐cecal reection
Interventions	Mesalamine (Pentasa®) 3g/day or placebo for 12 months
Outcomes	Clinical recurrence and severe endoscopic recurrence at 12 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Caprilli 2003

Methods	Prospective multi‐center randomised placebo controlledtrial
Participants	206 patients randomised following ileal or ileo‐colonic resection
Interventions	Eudragit‐S‐coated mesalamine (Asacol®) 4g/day or mesalamine 2.4g/day with placebo for 12 months
Outcomes	Clinical (CDAI>150) and endoscopic recurrence at 12 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Chermesh 2007

Methods	Multicenter randomised placebo controlled trial
Participants	30 patients randomised in a 2 to 1 ratio
Interventions	Synbiotic 2000 or placebo daily for up to 24 months
Outcomes	Clinical and endoscopic recurrence
Notes	Jadad score 3. Early termination of recruitment. Incomplete reporting of results
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	High risk	Early termination of recruitment. Incomplete reporting of results
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Colombel 2001

Methods	Multicenter randomised double blind placebo controlled trial
Participants	65 patients randomised following first ileal or ileocolonic resection
Interventions	Tenovil (IL‐10) 4 or 8 microg/kg or placebo for 3 months
Outcomes	Clinical, endoscopic and histologic recurrence at 3 months
Notes	Jadad score 3
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

D'Haens 2008

Methods	Multicenter randomised placebo controlled trial
Participants	81 patients randomised following ileal or ileocolonic resection
Interventions	Azathioprine 100mgs (<60kgs) or 150mgs (>60kgs) or placebo for 12 months with metronidazole 750mg/day for 3 months (both arms)
Outcomes	Clinical (CDAI>250) and endoscopic recurrence (Rutgeerts score>/=2) at 3 and 12 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Ewe 1989

Methods	Multi‐center randomised placebo controlled trial
Participants	232 patients randomised following either radical or non‐radical resection for Crohn's disease
Interventions	Sulphasalazine 3g/day or placebo for 3 years
Outcomes	Recurrence of Crohn's disease proven by either radiology, endoscopy or further surgery
Notes	Jadad score 3
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	High cumulative drop‐out rate but withdrawals and drop‐outs well described
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Ewe 1999

Methods	randomised multi‐center double‐blind placebo controlled trial
Participants	83 patients randomised following ileal, ileo‐colonic or colonic resection for Crohn's disease
Interventions	Budesonide 3mg/day or placebo for 12 months
Outcomes	Clinical, endoscopic and histologic recurrence at 12 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double‐blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Fiasse 1991

Methods	randomised placebo controlled trial
Participants	48 patients with Crohn's disease who underwent intestinal resection
Interventions	Eudragid‐L‐coated 5‐aminosalicylic acid 1.5g/day or placebo for 12 months
Outcomes	Clinical and endoscopic recurrence
Notes	Jadad score 2 Abstract only available for review Only preliminary results only are reported.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Unclear risk	Not described
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The abstract includes all expected outcomes

Florent 1996

Methods	Multi‐center randomised double‐blind placebo controlled trial
Participants	126 patients randomised following curative ileal/colonic resection
Interventions	Eudragit‐L mesalamine (Claversal®) 3g/day or placebo for 12 weeks
Outcomes	Endoscopic recurrence at 12 weeks
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Randomisation was carried out with a permutation table at each center
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Hanauer 2004

Methods	Multi‐center randomised double‐blind double dummy placebo controlled trial
Participants	131 patients randomised following ileocolic resection and anastomosis
Interventions	6‐mercaptopurine 50mg/day or mesalamine 3g/day or placebo for 24 months
Outcomes	Clinical, endoscopic and radiologic recurrence at 24 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Unclear risk	Manuscript reports percentages without absolute numbers associated

Hellers 1999

Methods	randomised, multi‐center, double‐blind, placebo controlled trial
Participants	130 patients randomised following ileocolonic resection for Crohn's disease
Interventions	Budesonide (controlled ileal release) 6mg/day or placebo for 12 months
Outcomes	Endoscopic recurrence and CDAI scores to 12 months.
Notes	Jadad score 3
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Herfarth 2006

Methods	Double dummy, double blind, randomised placebo controlled trial
Participants	79 patients with randomised within two weeks of intestinal resection for Crohn's disease
Interventions	Azathioprine 2‐2.5mg/kg or 5‐ASA (Salofalk®, Eudragit‐L mesalamine) 4g daily
Outcomes	Clinical and endoscopic recurrence. Withdrawal due to clinical relapse or adverse drug reaction.
Notes	Jadad score 2. Trial stopped early due to inadequate sample size Unpublished data from Peyrin‐Birloulet, 2009
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Unclear risk	Trial stopped early due to inadequate sample size

Lochs 2000

Methods	randomised, multi‐center, double‐blind, placebo controlled trial
Participants	324 patients randomised following intestinal resection for Crohn's disease
Interventions	Mesalamine (Pentasa®) 4g/day or placebo for 18 months
Outcomes	Clinical or endoscopic recurrence at 18 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Madsen 2008

Methods	Multi‐center randomised double‐blind placebo controlled trial
Participants	120 patients randomised following ileocolonic resection
Interventions	VSL#3 or placebo for 3 months
Outcomes	Endoscopic recurrence at 3 months
Notes	Jadad score 2 Results only published in abstract form to date
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	No described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	High risk	No description of dropouts or withdrawals
Free of selective reporting?	Unclear risk	Pre‐specified outcomes were reported but some other post‐hoc outcomes are reported too

Marteau 2006

Methods	Multi‐center randomised double‐blind placebo controlled trial
Participants	98 patients randomised following CD resection
Interventions	LA1 twice daily or placebo for 6 months
Outcomes	Clinical and endoscopic recurrence at 6 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Random number table
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

McLeod 1995

Methods	randomised, multi‐center, double‐blind, placebo controlled trial
Participants	163 patients randomised following intestinal resection for Crohn's disease
Interventions	Eudragit‐L mesalamine 3g/day or placebo for up to 72 months
Outcomes	Primary outcome ‐ symptomatic (clinical recurrence) recurrence within follow up
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Nos 2000

Methods	Prospective comparative study
Participants	39 patients following ileal or ileocecal resection
Interventions	Azathioprine 50mg/day or Mesalamine 3g/day for 24 months
Outcomes	Clinical or morphologic (radiologic/endoscopic) or serologic recurrence up to 24 months
Notes	Randomization and placebo control unclear. Jadad score 2
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Unclear risk	Not described
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Unclear risk	Not described

Prantera 2002

Methods	randomised, double ‐blind, placebo controlled trial
Participants	45 patients randomised following resection for Crohn's
Interventions	Lactobacillus GG (6 billion CFU) or placebo for 52 weeks
Outcomes	Clinical or endoscopic recurrence at 52 weeks
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Regueiro 2009

Methods	Single centre randomised, double‐blind, placebo controlled trial
Participants	24 adult patient undergoing resection and anastomosis for ileal or ileo‐colonic Crohn's disease
Interventions	Infliximab infusion (5mg/kg) or placebo at 0,2 and 6 weeks and subsequently at 8 week intervals for 54 weeks
Outcomes	Endoscopic recurrence (primary outcome, Rutgeerts score I2 or greater) and clinical (CDAI>200), histologic and biochemical activity scores (secondary outcomes) at 1 year
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Patients were randomised in blocks
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Rutgeerts 1995

Methods	randomised, double ‐blind, placebo controlled trial
Participants	60 patients randomised undergoing first ileocolonic resection for ileal Crohn's
Interventions	Metronidazole 20mg/kg/day or placebo for 3 months
Outcomes	Clinical (symptomatic), endoscopic or histologic recurrence in follow up to 3 years
Notes	Jadad score 3
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Rutgeerts 2005

Methods	randomised, double ‐blind, placebo controlled trial
Participants	80 patients randomised undergoing ileocolonic resection for ileal or ileocolonic Crohn's
Interventions	Ornidazole 1g/day or placebo for 54 weeks
Outcomes	Clinical (symptomatic with CDAI>250), endoscopic or histologic recurrence at 3 months and 1 year
Notes	Jadad score 3
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Not described
Allocation concealment?	Unclear risk	Not described
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Van Gossum 2007

Methods	Multi‐center randomised double‐blind placebo controlled trial
Participants	70 patients randomised following ileocecal resection
Interventions	LA1 or placebo for 3 months
Outcomes	Clinical, endoscopic and histologic recurrence at 3 months
Notes	Jadad score 5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Centralized randomisation
Allocation concealment?	Low risk	Adequate
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups
Free of selective reporting?	Low risk	The published report includes all expected outcomes

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Abdelli 2007	Not a randomised trial
Achkar 2000	Not a randomised trial
Achkar 2001	Not a randomised trial
Alves 2004	Not a randomised trial
Ambrose 1985	Treatment, not prevention study
Ardizzone 2003	Not a randomised trial
Bakkevold 2000	Non‐medical intervention
Belluzzi 1996	Treatment, not prevention study
Bemelman 2001	Not a randomised trial
Berebbi 1993	Not a randomised trial
Bergman 1976	Absence of placebo control. No blinding to treatment allocation possible.
Biancone 2006	Not a randomised trial
Blumberg 1990	Not a randomised trial
Borley 1997	Not a randomised trial
Cameron 1992	Non‐medical intervention
Caprilli 1994	Absence of placebo control. No blinding to treatment allocation possible.
Caprilli 1996	Not a randomised trial
Cottone 2003	Not a randomised trial
Cuillerier 2001	Not a randomised trial
D'Haens 1999a	Not a randomised trial
D'Haens 1999b	Not a randomised trial
de Jong 2007	Treatment, not prevention study
Dirks 1989	Treatment, not prevention study
Domenech 2004	Not a randomised trial
Domenech 2008	Not a randomised trial
Ellis 2006	Non‐medical intervention
Esaki 2005	Not a randomised trial
Ewe 1976	Duplicate
Ewe 1980	Duplicate
Ewe 1981	Duplicate
Ewe 1984	Duplicate
Fazio 1996	Non‐medical intervention
Feagan 1994	Treatment, not prevention study
Feagan 2003	Not a randomised trial
Fedorak 2000	Treatment, not prevention study
Froehlich 2005	Not a randomised trial
Garcia 2001	Not a randomised trial
Gardiner 2007	Not a randomised trial
Ghidirim 2007	Not a randomised trial
Gooszen 1994	Not a randomised trial
Gross 1995	Not a randomised trial
Hamedani 1997	Not a randomised trial
Hanauer 2003	Not a randomised trial
Hancock 2006	Not a randomised trial
Ikeuchi 2000	Non‐medical intervention
Kader 1997	Not a randomised trial
Kennedy 1998	Not a randomised trial
Klein 1995	Not a randomised trial
Koop 1994	Not a randomised trial
Korelitz 1998	Duplicate
Kusunoki 1998	Non‐medical intervention
Lemann 2006a	Not a randomised trial
Lemann 2006b	Treatment, not prevention study
Levenstein 1985	Treatment, not prevention study
MacDonald 2006	Not a randomised trial
Mahmud 2001	Treatment, not prevention study
Mamula 2000	Not a randomised trial
McIntyre 1986	Treatment, not prevention study
McLeod 1996	Not a randomised trial
Mekhijan 1979	Not a randomised trial
Morretini 1981	Not a randomised trial
Myrelid 2006	Not a randomised trial
O'Brien 1991	Treatment, not prevention study
Prantera 1999	Not a randomised trial
Qasim 2001	Not a randomised trial
Regimbeau 1999	Not a randomised trial
Reinisch 2008	Treatment, not prevention study
Rutgeerts 2003	Non‐randomised intervention
Ryan 2004	Non‐randomised intervention
Sandborn 2004	Not a randomised trial
Scarpa 2007	Not a randomised trial
Seibold 2003	Not a randomised trial
Sninsky 2001	Not a randomised trial
Sorrentino 2006	Not a randomised trial
Sorrentino 2007	Not a randomised trial
Stein 1999	Not a randomised trial
Steinhart 1992	Not a randomised trial
Steinhart 2007	Not a randomised trial
Sutherland 2000	Not a randomised trial
Tay 2003	Not a randomised trial
Travis 2001	Not a randomised trial
Van Assche 2004	Not a randomised trial
Van Hogezand 1998	Not a randomised trial
Viscido 1999	Non‐medical intervention
Volk‐Zeiher 1998	Not a randomised trial
Yamamoto 2005	Not a randomised trial
Yamamoto 2007	Not a randomised trial

Data and analyses

Open in table viewer

Comparison 1. Probiotics vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence Show forest plot	3	213	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [0.59, 3.36]
Open in figure viewer Analysis 1.1 Comparison 1 Probiotics vs Placebo, Outcome 1 Clinical Recurrence.
2 Any Endoscopic Recurrence Show forest plot	3	213	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.74, 1.29]
Open in figure viewer Analysis 1.2 Comparison 1 Probiotics vs Placebo, Outcome 2 Any Endoscopic Recurrence.
3 Severe Endoscopic Recurrence Show forest plot	4	333	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.58, 1.58]
Open in figure viewer Analysis 1.3 Comparison 1 Probiotics vs Placebo, Outcome 3 Severe Endoscopic Recurrence.
4 Patient Withdrawal Show forest plot	3	213	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.65, 1.75]
Open in figure viewer Analysis 1.4 Comparison 1 Probiotics vs Placebo, Outcome 4 Patient Withdrawal.
5 Serious Adverse Events Show forest plot	3	213	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.35, 1.52]
Open in figure viewer Analysis 1.5 Comparison 1 Probiotics vs Placebo, Outcome 5 Serious Adverse Events.

Open in table viewer

Comparison 2. Nitroimidazole vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence (12 months) Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.09, 0.57]
Open in figure viewer Analysis 2.1 Comparison 2 Nitroimidazole vs Placebo, Outcome 1 Clinical Recurrence (12 months).
2 Severe (score >/=2) Endoscopic Recurrence (3months) Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.26, 0.74]
Open in figure viewer Analysis 2.2 Comparison 2 Nitroimidazole vs Placebo, Outcome 2 Severe (score >/=2) Endoscopic Recurrence (3months).
3 Patient Withdrawal Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [1.37, 6.58]
Open in figure viewer Analysis 2.3 Comparison 2 Nitroimidazole vs Placebo, Outcome 3 Patient Withdrawal.
4 Serious Adverse Events Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	2.39 [1.54, 3.70]
Open in figure viewer Analysis 2.4 Comparison 2 Nitroimidazole vs Placebo, Outcome 4 Serious Adverse Events.

Open in table viewer

Comparison 3. 5‐ASA vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence (at study completion) Show forest plot	4	652	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.62, 0.94]
Open in figure viewer Analysis 3.1 Comparison 3 5‐ASA vs Placebo, Outcome 1 Clinical Recurrence (at study completion).
2 Any Endoscopic Recurrence (at study completion) Show forest plot	4	615	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.76, 1.13]
Open in figure viewer Analysis 3.2 Comparison 3 5‐ASA vs Placebo, Outcome 2 Any Endoscopic Recurrence (at study completion).
3 Severe (score>/=3) Endoscopic Recurrence (at study completion) Show forest plot	3	297	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.29, 0.84]
Open in figure viewer Analysis 3.3 Comparison 3 5‐ASA vs Placebo, Outcome 3 Severe (score>/=3) Endoscopic Recurrence (at study completion).
4 Patient Withdrawal Show forest plot	5	788	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.89, 1.39]
Open in figure viewer Analysis 3.4 Comparison 3 5‐ASA vs Placebo, Outcome 4 Patient Withdrawal.
5 Serious Adverse Events Show forest plot	5	788	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.62, 1.66]
Open in figure viewer Analysis 3.5 Comparison 3 5‐ASA vs Placebo, Outcome 5 Serious Adverse Events.

Open in table viewer

Comparison 4. 5‐ASA vs Azathioprine/6MP

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence within 12 months Show forest plot	4	349	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.95, 2.16]
Open in figure viewer Analysis 4.1 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 1 Clinical Recurrence within 12 months.
2 Clinical recurrence within 24 months Show forest plot	3	270	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [0.95, 1.81]
Open in figure viewer Analysis 4.2 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 2 Clinical recurrence within 24 months.
3 Any endoscopic recurrence (score >/=1) within 12 months Show forest plot	2	130	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [1.03, 2.06]
Open in figure viewer Analysis 4.3 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 3 Any endoscopic recurrence (score >/=1) within 12 months.
4 Severe endoscopic recurrence (score >/=2) within 12 months Show forest plot	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.94, 2.29]
Open in figure viewer Analysis 4.4 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 4 Severe endoscopic recurrence (score >/=2) within 12 months.
5 Very Severe endoscopic recurrence (score >/=3) within 12 months Show forest plot	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.63, 3.79]
Open in figure viewer Analysis 4.5 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 5 Very Severe endoscopic recurrence (score >/=3) within 12 months.
6 Patient Withdrawal Show forest plot	3	268	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.59, 1.26]
Open in figure viewer Analysis 4.6 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 6 Patient Withdrawal.
7 Serious Adverse Events Show forest plot	4	347	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.30, 0.89]
Open in figure viewer Analysis 4.7 Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 7 Serious Adverse Events.

Open in table viewer

Comparison 5. Azathioprine/6MP vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence at 12 months Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.38, 0.92]
Open in figure viewer Analysis 5.1 Comparison 5 Azathioprine/6MP vs Placebo, Outcome 1 Clinical Recurrence at 12 months.
2 Severe Endoscopic Recurrence (score>/=2) at 12 months Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.44, 0.92]
Open in figure viewer Analysis 5.2 Comparison 5 Azathioprine/6MP vs Placebo, Outcome 2 Severe Endoscopic Recurrence (score>/=2) at 12 months.
3 Patient Withdrawal Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.51, 1.00]
Open in figure viewer Analysis 5.3 Comparison 5 Azathioprine/6MP vs Placebo, Outcome 3 Patient Withdrawal.
4 Serious Adverse Events Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.61 [0.71, 3.66]
Open in figure viewer Analysis 5.4 Comparison 5 Azathioprine/6MP vs Placebo, Outcome 4 Serious Adverse Events.

Open in table viewer

Comparison 6. Azathioprine/6MP versus Other Intervention (5ASA or placebo)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence at 12 months Show forest plot	5	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.45, 0.92]
Open in figure viewer Analysis 6.1 Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 1 Clinical Recurrence at 12 months.
2 Severe Endoscopic Recurrence (score>/=2) at 12 months Show forest plot	3	291	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.49, 0.93]
Open in figure viewer Analysis 6.2 Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 2 Severe Endoscopic Recurrence (score>/=2) at 12 months.
3 Patient Withdrawal Show forest plot	4	389	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.69, 1.26]
Open in figure viewer Analysis 6.3 Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 3 Patient Withdrawal.
4 Serious Adverse Events Show forest plot	5	468	Risk Ratio (M‐H, Fixed, 95% CI)	1.87 [1.16, 3.02]
Open in figure viewer Analysis 6.4 Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 4 Serious Adverse Events.

Open in table viewer

Comparison 7. Budesonide vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severe Endoscopic Recurrence (12 months) Show forest plot	2	212	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.50, 1.49]
Open in figure viewer Analysis 7.1 Comparison 7 Budesonide vs Placebo, Outcome 1 Severe Endoscopic Recurrence (12 months).
2 Patient Withdrawal Show forest plot	2	212	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.80, 1.86]
Open in figure viewer Analysis 7.2 Comparison 7 Budesonide vs Placebo, Outcome 2 Patient Withdrawal.
3 Serious Adverse Events Show forest plot	2	212	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.37, 2.78]
Open in figure viewer Analysis 7.3 Comparison 7 Budesonide vs Placebo, Outcome 3 Serious Adverse Events.

Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 2

Forest plot of comparison: 3 Probiotics vs Placebo, outcome: 3.1 Clinical Recurrence.

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Figure 3

Forest plot of comparison: 3 Probiotics vs Placebo, outcome: 3.3 Severe endoscopic recurrence.

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Figure 4

Forest plot of comparison: 3 Probiotics vs Placebo, outcome: 3.2 Any endoscopic recurrence.

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Figure 5

Forest plot of comparison: 5 Nitroimidazole vs Placebo, outcome: 5.1 Severe Endoscopic Recurrence (3months).

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Figure 6

Forest plot of comparison: 5 Nitroimidazole vs Placebo, outcome: 5.2 Clinical Recurrence (1 year).

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Figure 7

Forest plot of comparison: 2 Nitroimidazole vs Placebo, outcome: 2.3 Patient Withdrawal.

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Figure 8

Forest plot of comparison: 1 5‐ASA vs Placebo, outcome: 1.1 Clinical Recurrence within 12 months.

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Figure 9

Forest plot of comparison: 1 5‐ASA vs Placebo, outcome: 1.2 Any endoscopic recurrence within 12 months.

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Figure 10

Forest plot of comparison: 1 5‐ASA vs Placebo, outcome: 1.3 Severe (score>/=3) endoscopic recurrence within 12 months.

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Figure 11

Forest plot of comparison: 2 5‐ASA vs Azathioprine/6MP, outcome: 2.1 Clinical Recurrence within 12 months.

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Figure 12

Forest plot of comparison: 2 5‐ASA vs Azathioprine/6MP, outcome: 2.2 Any endoscopic recurrence within 12 months.

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Figure 13

Forest plot of comparison: 2 5‐ASA vs Azathioprine/6MP, outcome: 2.3 Severe (>/=3 score) within 12 months.

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Figure 14

Forest plot of comparison: 5 Azathioprine/6MP vs placebo, outcome: 5.1 Clinical recurrence at 12 months.

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Figure 15

Forest plot of comparison: 5 Azathioprine/6MP vs placebo, outcome: 5.2 Severe endoscopic recurrence (score>/=2) at 12 months.

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Figure 16

Forest plot of comparison: 4 Budesonide vs Placebo, outcome: 4.1 Severe Endoscopic Recurrence (12 months).

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Figure 17

Forest plot of comparison: 6 Azathioprine/6MP versus other interventions (5ASA or placebo), outcome: 6.1 Clinical recurrence at 12 months.

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Figure 18

Forest plot of comparison: 6 Azathioprine/6MP versus other interventions (5ASA or placebo), outcome: 6.2 Severe endoscopic recurrence (score>/=2) at 12 months.

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Analysis 1.1

Comparison 1 Probiotics vs Placebo, Outcome 1 Clinical Recurrence.

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Analysis 1.2

Comparison 1 Probiotics vs Placebo, Outcome 2 Any Endoscopic Recurrence.

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Analysis 1.3

Comparison 1 Probiotics vs Placebo, Outcome 3 Severe Endoscopic Recurrence.

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Analysis 1.4

Comparison 1 Probiotics vs Placebo, Outcome 4 Patient Withdrawal.

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Analysis 1.5

Comparison 1 Probiotics vs Placebo, Outcome 5 Serious Adverse Events.

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Analysis 2.1

Comparison 2 Nitroimidazole vs Placebo, Outcome 1 Clinical Recurrence (12 months).

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Analysis 2.2

Comparison 2 Nitroimidazole vs Placebo, Outcome 2 Severe (score >/=2) Endoscopic Recurrence (3months).

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Analysis 2.3

Comparison 2 Nitroimidazole vs Placebo, Outcome 3 Patient Withdrawal.

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Analysis 2.4

Comparison 2 Nitroimidazole vs Placebo, Outcome 4 Serious Adverse Events.

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Analysis 3.1

Comparison 3 5‐ASA vs Placebo, Outcome 1 Clinical Recurrence (at study completion).

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Analysis 3.2

Comparison 3 5‐ASA vs Placebo, Outcome 2 Any Endoscopic Recurrence (at study completion).

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Analysis 3.3

Comparison 3 5‐ASA vs Placebo, Outcome 3 Severe (score>/=3) Endoscopic Recurrence (at study completion).

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Analysis 3.4

Comparison 3 5‐ASA vs Placebo, Outcome 4 Patient Withdrawal.

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Analysis 3.5

Comparison 3 5‐ASA vs Placebo, Outcome 5 Serious Adverse Events.

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Analysis 4.1

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 1 Clinical Recurrence within 12 months.

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Analysis 4.2

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 2 Clinical recurrence within 24 months.

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Analysis 4.3

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 3 Any endoscopic recurrence (score >/=1) within 12 months.

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Analysis 4.4

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 4 Severe endoscopic recurrence (score >/=2) within 12 months.

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Analysis 4.5

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 5 Very Severe endoscopic recurrence (score >/=3) within 12 months.

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Analysis 4.6

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 6 Patient Withdrawal.

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Analysis 4.7

Comparison 4 5‐ASA vs Azathioprine/6MP, Outcome 7 Serious Adverse Events.

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Analysis 5.1

Comparison 5 Azathioprine/6MP vs Placebo, Outcome 1 Clinical Recurrence at 12 months.

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Analysis 5.2

Comparison 5 Azathioprine/6MP vs Placebo, Outcome 2 Severe Endoscopic Recurrence (score>/=2) at 12 months.

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Analysis 5.3

Comparison 5 Azathioprine/6MP vs Placebo, Outcome 3 Patient Withdrawal.

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Analysis 5.4

Comparison 5 Azathioprine/6MP vs Placebo, Outcome 4 Serious Adverse Events.

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Analysis 6.1

Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 1 Clinical Recurrence at 12 months.

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Analysis 6.2

Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 2 Severe Endoscopic Recurrence (score>/=2) at 12 months.

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Analysis 6.3

Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 3 Patient Withdrawal.

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Analysis 6.4

Comparison 6 Azathioprine/6MP versus Other Intervention (5ASA or placebo), Outcome 4 Serious Adverse Events.

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Analysis 7.1

Comparison 7 Budesonide vs Placebo, Outcome 1 Severe Endoscopic Recurrence (12 months).

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Analysis 7.2

Comparison 7 Budesonide vs Placebo, Outcome 2 Patient Withdrawal.

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Analysis 7.3

Comparison 7 Budesonide vs Placebo, Outcome 3 Serious Adverse Events.

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Comparison 1. Probiotics vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence Show forest plot	3	213	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [0.59, 3.36]

2 Any Endoscopic Recurrence Show forest plot	3	213	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.74, 1.29]

3 Severe Endoscopic Recurrence Show forest plot	4	333	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.58, 1.58]

4 Patient Withdrawal Show forest plot	3	213	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.65, 1.75]

5 Serious Adverse Events Show forest plot	3	213	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.35, 1.52]

Comparison 1. Probiotics vs Placebo

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Comparison 2. Nitroimidazole vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence (12 months) Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.09, 0.57]

2 Severe (score >/=2) Endoscopic Recurrence (3months) Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.26, 0.74]

3 Patient Withdrawal Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [1.37, 6.58]

4 Serious Adverse Events Show forest plot	2	140	Risk Ratio (M‐H, Fixed, 95% CI)	2.39 [1.54, 3.70]

Comparison 2. Nitroimidazole vs Placebo

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Comparison 3. 5‐ASA vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence (at study completion) Show forest plot	4	652	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.62, 0.94]

2 Any Endoscopic Recurrence (at study completion) Show forest plot	4	615	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.76, 1.13]

3 Severe (score>/=3) Endoscopic Recurrence (at study completion) Show forest plot	3	297	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.29, 0.84]

4 Patient Withdrawal Show forest plot	5	788	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.89, 1.39]

5 Serious Adverse Events Show forest plot	5	788	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.62, 1.66]

Comparison 3. 5‐ASA vs Placebo

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Comparison 4. 5‐ASA vs Azathioprine/6MP

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence within 12 months Show forest plot	4	349	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.95, 2.16]

2 Clinical recurrence within 24 months Show forest plot	3	270	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [0.95, 1.81]

3 Any endoscopic recurrence (score >/=1) within 12 months Show forest plot	2	130	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [1.03, 2.06]

4 Severe endoscopic recurrence (score >/=2) within 12 months Show forest plot	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.94, 2.29]

5 Very Severe endoscopic recurrence (score >/=3) within 12 months Show forest plot	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.63, 3.79]

6 Patient Withdrawal Show forest plot	3	268	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.59, 1.26]

7 Serious Adverse Events Show forest plot	4	347	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.30, 0.89]

Comparison 4. 5‐ASA vs Azathioprine/6MP

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Comparison 5. Azathioprine/6MP vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence at 12 months Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.38, 0.92]

2 Severe Endoscopic Recurrence (score>/=2) at 12 months Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.44, 0.92]

3 Patient Withdrawal Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.51, 1.00]

4 Serious Adverse Events Show forest plot	2	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.61 [0.71, 3.66]

Comparison 5. Azathioprine/6MP vs Placebo

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Comparison 6. Azathioprine/6MP versus Other Intervention (5ASA or placebo)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Recurrence at 12 months Show forest plot	5	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.45, 0.92]

2 Severe Endoscopic Recurrence (score>/=2) at 12 months Show forest plot	3	291	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.49, 0.93]

3 Patient Withdrawal Show forest plot	4	389	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.69, 1.26]

4 Serious Adverse Events Show forest plot	5	468	Risk Ratio (M‐H, Fixed, 95% CI)	1.87 [1.16, 3.02]

Comparison 6. Azathioprine/6MP versus Other Intervention (5ASA or placebo)

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Comparison 7. Budesonide vs Placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severe Endoscopic Recurrence (12 months) Show forest plot	2	212	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.50, 1.49]

2 Patient Withdrawal Show forest plot	2	212	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.80, 1.86]

3 Serious Adverse Events Show forest plot	2	212	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.37, 2.78]

Comparison 7. Budesonide vs Placebo

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Referencias

Referencias de los estudios incluidos en esta revisión

Ardizzone 2004 {published data only}

Brignola 1995 {published data only}

Caprilli 2003 {published data only}

Chermesh 2007 {published data only}

Colombel 2001 {published data only}

D'Haens 2008 {published data only}

Ewe 1989 {published data only}

Ewe 1999 {published data only}

Fiasse 1991 {published data only}

Florent 1996 {published data only}

Hanauer 2004 {published data only}

Hellers 1999 {published data only}

Herfarth 2006 {published and unpublished data}

Lochs 2000 {published data only}

Madsen 2008 {published data only}

Marteau 2006 {published data only}

McLeod 1995 {published data only}

Nos 2000 {published data only}

Prantera 2002 {published data only}

Regueiro 2009 {published data only}

Rutgeerts 1995 {published data only}

Rutgeerts 2005 {published data only}

Van Gossum 2007 {published data only}

Referencias de los estudios excluidos de esta revisión

Abdelli 2007 {published data only}

Achkar 2000 {published data only}

Achkar 2001 {published data only}

Alves 2004 {published data only}

Ambrose 1985 {published data only}

Ardizzone 2003 {published data only}

Bakkevold 2000 {published data only}

Belluzzi 1996 {published data only}

Bemelman 2001 {published data only}

Berebbi 1993 {published data only}

Bergman 1976 {published data only}

Biancone 2006 {published data only}

Blumberg 1990 {published data only}

Borley 1997 {published data only}

Cameron 1992 {published data only}

Caprilli 1994 {published data only}

Caprilli 1996 {published data only}

Cottone 2003 {published data only}

Cuillerier 2001 {published data only}

D'Haens 1999a {published data only}

D'Haens 1999b {published data only}

de Jong 2007 {published data only}

Dirks 1989 {published data only}

Domenech 2004 {published data only}

Domenech 2008 {published data only}

Ellis 2006 {published data only}

Esaki 2005 {published data only}

Ewe 1976 {published data only}

Ewe 1980 {published data only}

Ewe 1981 {published data only}

Ewe 1984 {published data only}

Fazio 1996 {published data only}

Feagan 1994 {published data only}

Feagan 2003 {published data only}

Fedorak 2000 {published data only}

Froehlich 2005 {published data only}

Garcia 2001 {published data only}

Gardiner 2007 {published data only}

Ghidirim 2007 {published data only}

Gooszen 1994 {published data only}

Gross 1995 {published data only}

Hamedani 1997 {published data only}

Hanauer 2003 {published data only}

Hancock 2006 {published data only}

Ikeuchi 2000 {published data only}

Kader 1997 {published data only}

Kennedy 1998 {published data only}

Klein 1995 {published data only}

Koop 1994 {published data only}

Korelitz 1998 {published data only}

Kusunoki 1998 {published data only}

Lemann 2006a {published data only}