. 2021 Dec 17;8(1):e000702. doi: 10.1136/bmjgast-2021-000702

Table 2.

Selected studies for systematic review and meta-analysis

Author	Publication year	Type of study	Type of manuscript	Origin	Centres	Time frame	Patients with perianal fistula	Definition of response	Definition of remission	First time frame	Patients with response	Patients in remission	Second time frame	Patients with improvement	Patients in remission	Third time frame	Patients with improvement	Patients in remission
Harris et al¹¹	2020	Retrospective observational	Full manuscript	UK	1	Unspecified	8	Improvement in PGA category	Unspecified	Median 14.7 weeks (IQR 5–21)	3/8	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Weaver et al²⁰	2019	Retrospective observational	Full manuscript	USA	4	2013–2018	19	Decrease in fistula drainage	Unspecified	6 months	9/11	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Chavannes et al²¹	2019	Retrospective observational	Full manuscript	Canada, USA, France, Australia	4	2014–2018	2	Changes in mean aPCDAI)	aPCDAI <10	6 months	0/2	0/2	12 months	0/1	0/1	N/A	N/A	N/A
Krugliack et al²²	2018	Retrospective cohort	Abstract	USA	1	2013–2017	16	Clinical assessment: cessation of drainage and no abscess	Unspecified	6 months	10/16	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Satyam et al¹³	2018	Retrospective observational	Abstract	USA	1	2013–2017	21	Improvement in perianal symptoms as assessed by a treating physician and continuation of ustekinumab	Complete absence of perianal symptoms on history, physical exam and endoscopy if available	Mean 382 days (64–1271)	7/21	2/21	N/A	N/A	N/A	N/A	N/A	N/A
Battat et al²³	2017	Case series	Abstract	Canada	1	2013–2015	6	>50% reduction from baseline in the number of draining fistulas	Closure of all fistulas	>6 months	4/6	2/6	N/A	N/A	N/A	N/A	N/A	N/A
Tsistrakis and Oikonomou²⁴	2017	Retrospective observational	Abstract	USA	1	2016–2017	6	Decrease in fistulous drainage or partial healing of fistulas	Complete closure of fistula	3 months	2/5	1/5	N/A	N/A	N/A	N/A	N/A	N/A
Ma et al²⁵	2017	Retrospective cohort	Full manuscript	Canada	2	2011–2016	45	Reduction in number of draining fistulas by 50% compared with baseline as assessed by physical exam without the need for surgical interventions including exam under anesthesia, fistulotomy or seton placement	Complete absence of fistula drainage on patient history and closure of all fistulas on physical exam	12 months	22/45	12/45	N/A	N/A	N/A	N/A	N/A	N/A
Sands¹⁵	2017	Randomized prospective clinical trial	Abstract	USA, Canada, Belgium, South Africa, UK	260	2011–2015	161	>50% reduction in draining fistulas	100% fistula reduction	8 weeks	39/150	37/150	22 weeks	9/19	N/A	44 weeks	12/15	NA
Khorrami et al¹²	2016	Retrospective observational	Full manuscript	Spain	42	2010–2014	18	Physician judgement	Unspecified	Median 10 months (IQR 5–21)	11/18	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Bishop et al¹⁰	2016	Paediatric case series	Full manuscript	USA	1	2013–2014	2	Unspecified	Unspecified	Mean 11 months±4.9	½	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Wils et al¹⁴	2018	Retrospective observational	Full manuscript	France, Switzerland	20	2011–2014	12	Significant improvement in CD-related clinical symptoms and laboratory tests assessed by the patient’s physician leading to continued ustekinumab treatment, associated with complete weaning from steroids if they were being taken at inclusion, without surgery or immunosuppressant introduction	Unspecified	Median 12 weeks (39.2±32.8)	8/12	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Kopylov et al²⁶	2014	Retrospective observational	Full manuscript	Canada	1	2011–2013	13	Improvement in the patient’s symptoms coupled with the decision to continue ustekinumab treatment Physician’s assessment	Unspecified	12 weeks	9/13	N/A	12 months	¾	N/A	N/A	N/A	N/A
Attauabi et al²⁷	2020	Retrospective cohort	Full manuscript	Denmark	2	2015–2020	18	Fistula response was defined as a combination of the physician’s objective assessment and the patient’s self-reported improvement in disease symptoms without the need for surgical procedures compared with baseline.	Fistula remission was defined as healing with no secretion or symptomatic activity.	8 weeks	3/18	0/18	24 weeks	6/12	0/12	52 weeks	7/11	N/A
Straatmijer et al²⁸	2021	Prospective cohort	Full manuscript	The Netherlands	8	Unspecified	29	Clinical response (at least three points HBI reduction)	Corticosteroid-free clinical remission (HBI ≤4)	12 weeks	5/29	N/A	24 weeks	11/29	N/A	52 weeks	11/29	N/A
Plevris et al²⁹	2020	Retrospective cohort	Full manuscript	Israel	14	2017–2019	37	Perianal response was determined by follow-up MRI (reduction in enhancement, closure or fibrosis of tract compared with baseline MRI)	Unspecified	24 weeks	3/24	N/A	52 weeks	4/7	N/A	NA	N/A	N/A
Bar-Gil Shitrit et al³⁰	2020	Prospective cohort	Full manuscript	Israel	8	Unspecified	26	Patients were described as having or stopped having perianal fistulas, which were described as actively draining perianal fistula.	Unspecified	8 weeks	6/26	N/A	24 weeks	8/26	N/A	N/A	N/A	N/A
Tursi et al³¹	2021	Retrospective cohort	Full manuscript	Italy	25	Up to 2019	27	HBS <5 after 3 months of follow-up	Unspecified	8 weeks	16/27	16/27	Mean of 12 months	14/27	14/27	N/A	N/A	N/A
Miyazaki et al³²	2019	Retrospective cohort	Full manuscript	Japan	1	2017–2018	9	Decrease in CDAI of >100 points from the baseline	CDA<150 points	8 weeks	2/9	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Bacaksız et al³³	2021	Retrospective cohort	Full manuscript	Turkey	1	2018	5	Clinical response was defined as a decrease of 70 points in CDAI score; a decrease of 3 points in the HBI was accepted as clinical response.	Clinical remission was defined as a CDAI score of <150; an HBI score of 4 was accepted as clinical remission.	8 weeks	4/5	2/5	52 weeks	2/2	2/2	N/A	N/A	N/A
Marquès-Camí et al³⁴	2020	Retrospective cohort	Full manuscript	Spain	1	2009–2019	8	The CDAI²³ was used to evaluate disease activity, and the long-term clinical remission was defined by a cut-off of less than 150 points during the 52 weeks of treatment.	The CDAI²³ was used to evaluate disease activity, and the long-term clinical remission was defined by a cut-off of less than 150 points during the 52 weeks of treatment.	52 weeks	5/8	5/8	N/A	N/A	N/A	N/A	N/A	N/A
Manlay et al³⁵	2021	Retrospective cohort	Full manuscript	France	2	2014–2020	39	Unspecified	Deep remission (=combination of corticosteroid-free clinical remission and deep biological remission), active perianal lesions (defined as the persistence of draining, perianal pain or abscesses	14 weeks	N/A	17/36	24 weeks	N/A	15/30	54 weeks	N/A	14/21
Yokoyama et al³²	2021	Retrospective cohort	Full manuscript	Japan	91	2017–2020	65	Clinical response (defined as reduction from baseline in the CDAI score of ≥100 points)	Clinical remission (defined as a CDAI score of ≤150) at week 8	8 weeks	12/65	12/65	N/A	N/A	N/A	N/A	N/A	N/A
Chapuis-Biron et al⁹	2020	Prospective	Full manuscript	France	18	2020	148	Clinical success at 6 months of treatment assessed by the physicians’ judgement, with (1) no need for dedicated medical treatment for perianal lesions (antibiotics and/or topics) nor (2) unscheduled surgical treatment such as abscess drainage, fistulectomy, fistulotomy, seton drainage, stricture dilatation or abdominoperineal resection	Unspecified	Median 52.1 (19.6–69.4)	57/148	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Takeuchi et al³⁶	2020	Retrospective cohort	Full manuscript	Japan	1	By 2019	6	Weighted paediatric CD Activity Index (wPCDAI) was used to assess their disease activity. Clinical remission was defined as wPCDAI under 10, and steroid-free clinical remission was defined as clinical remission without corticosteroids. For patients who underwent ileocolonoscopy during their follow-up, the change in disease activity was assessed by using the simple endoscopic score for CD.	Clinical remission was defined as wPCDAI under 10, and steroid-free clinical remission was defined as clinical remission without corticosteroids.	26 weeks	2/6	0/6	N/A	N/A	N/A	N/A	N/A	N/A

aPCDAI, Abberviated Paediatric Crohn’s Disease Activity Index; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; HBI, Harvey-Bradshaw Index; N/A, not available; PCDAI, Paediatric Crohn’s Disease Activity Index; PGA, physician global assessment; wPCDAI, Weighted Paediatric Crohn’s Disease Activity Index.