Stem cell injection for complex anal fistula in Crohn’s disease: A single-center experience

Table 1 Inclusion and exclusion criteria for administration of darvadstrocel

Inclusion	Exclusion
Complex anal fistulas associated with Crohn’s disease (including horse-shoe fistula)	Simple fistulas associated with Crohn’s disease, rectovaginal fistula
At least one conventional, biological or surgical therapy prior to stem cell injection	No medical, biological or surgical therapy prior to stem cell injection
No active Crohn’s disease confirmed by ileocolonoscopy	Active Crohn’s disease confirmed by ileocolonoscopy
No perianal abscess or sepsis confirmed by clinical exam, endoanal ultrasound and/or pelvic MRI	Perianal abscess or significant inflammation in the pelvis or anorectal region confirmed by MRI
Interdisciplinary recommendation	No recommendation by multidisciplinary team
Patient compliant for medical consultation, follow-up examination and interdisciplinary monitoring of disease	Non-compliance of patient
Pretreatment of fistulas by seton drainage (“conditioning”)	Fistulas without seton drainage or conditioning by curettage
Maximum of two fistulas with two internal and two external openings (each)	More than two complex fistulas
No anorectal stenosis	Presence of anorectal stenosis
Fully informed consent possible	No informed consent possible

MRI: Magnetic resonance imaging.

Table 2 Definitions of outcome

Parameter	Definition	Supplementary definition
Healing	Complete healing of internal and external opening; no abscess, no symptoms	Assessment by clinical examination including proctoscopy
Persistence	No complete healing with persistence of fistula (external opening) and/or symptoms	Defined postoperative observation period
Recurrence	Recurrence of fistula after period with complete healing and interval without symptoms	With or without occurrence of abscess

Table 3 Patient population

	1	2	3	4	5	6	7	8	9	10	11	12
Age	26 yr	31 yr	52 yr	49 yr	39 yr	35 yr	61 yr	26 yr	54 yr	44 yr	45 yr	48 yr
Sex	Male	Female	Female	Female	Male	Female	Male	Female	Male	Male	Male	Female
CPF Parks classification (number of fistulas)	Transsphincteric (2)	Transsphincteric (2)	Suprasphincteric (1)	Transsphincteric (2)	Transsphincteric (1) Intersphincteric (1)	Transsphincteric (2)	Transsphincteric (2)	Transsphincteric (1)	Suprasphincteric (1) Transsphincteric (1)	Transsphincteric horse-shoe-fistula (2)	Transsphincteric horse-shoe-fistula (2)	Suprasphincteric (1)
Number of internal/external openings	2/2	2/2	1/1	2/2	2/2	1/2	2/2	1/1	2/2	1/2	1/2	1/1
Length of fistula tract	3 cm each	3 cm each	4 cm	2 cm; 5 cm	10 cm; 1.5 cm	12 cm; 1.5 cm	3 cm; 7 cm	3 cm	6.5 cm; 2.5 cm	2.5 cm; 2.5 cm	3.0 cm; 3.0 cm	3.0 cm
Previous medical treatment	Azathioprin	Azathioprin Infliximab	Azathioprin	Azathioprin	Azathioprin	Azathioprin	Azathioprin Infliximab	Azathioprin	Adalimumab	Azathioprin Adalimumab	Infliximab	Azathiopron Antibiotics
Actual medical treatment	Adalimumab	Ustekinumab	Azathioprin	None	Ustekinumab	Vedolizumab	Ustekinumab	Infliximab	Infliximab	Infliximab	Adalimumab	None
Previous surgical treatment for abscess and fistula	Multiple abscess excisions, previous fistula surgery (1)	Multiple abscess excisions, previous fistula surgery (1)	Multiple abscess excisions,previous fistula surgery (3)	Multiple abscess excisions, previous fistula surgery (2)	Multiple abscess excisions, previous fistula surgery (3)	Multiple abscess excisions, previous fistula surgery (2)	Multiple abscess and fistula surgeries (11)	Multiple abscess and fistula surgery (4)	Multiple abscess and fistula surgery (4)	Multiple abscess and fistula surgery (4)	Multiple abscess and fistula surgery (3)	Multiple abscess and fistula surgery (9)
Previous treatment (stoma)	No	Yes	No	Yes	No	No	No	No	No	Yes	Yes	No
Seton drainage prior to Darvadstrocel (duration)	Yes (6 wk)	Yes (4 mo)	Yes (10 mo)	Yes (18 mo)	Yes (8 wk)	Yes (12 wk)	Yes (9 mo)	Yes (60 wk)	Yes (36 wk)	Yes (48 wk)	Yes (24 wk)	Yes (12 wk)
Method of closure of internal opening	Suture (1), mucosal flap (1)	Suture (2)	Suture (1)	Suture (2)	Suture (2)	Suture (1)	Suture (2)	Suture (1)	Suture (2)	Suture (1)	Suture (1)	Suture (1)
Intraoperative adverse events	No	No	No	No	No	No	No	No	No	No	No	No
Postoperative adverse events	No	No	No	No	No	No	No	No	No	No	Fewer (day 2)	No

CD: Crohn’s disease; CPF: Crohn’s perianal fistula.

Table 4 Efficacy evaluation and outcomes

	1	2	3	4	5	6	7	8	9	10	11	12
Length of follow-up (mo)	27	30	8	24	26	16	12	6	8	6	6	3
Efficacy evaluation (clinical)	Complete healing	Complete healing	Complete healing	Recurrence	Persistence	Complete healing	Complete healing	Complete healing	Persistence	Complete healing	Recurrence	Complete healing
Efficacy evaluation (MRI)	Not performed	Complete healing	Not performed	Recurrence	Persistence	Not performed	Not performed	Not performed	Not performed	Persistence	Recurrence	Not performed
Time to fistula closure	6 wk	12 wk	9 wk	---	---	12 wk	30 wk	9 wk	--	9 wk	---	10 wk
Incidence of abscess during follow-up	Yes	No	No	No	Yes	No	No	No	Yes	No	Yes	No
Further surgery during follow-up	Yes; Abscess excision (twice)	No	No	Seton drainage	Yes; Abscess excision	No	No	No	Yes; Abscess excision	No	Yes; Abscess excision	No
Maintenance therapy	Adalimumab	Ustekinumab	Azathioprin	Infliximab	Ustekinumab	Vedolizumab	Ustekinumab	Ceased	Infliximab	Infliximab	Infliximab	None
Stoma reversal (if present)	No stoma	Stoma reversal	No stoma	No	No stoma	No stoma	No stoma	No stoma	No stoma	No	No	No stoma

MRI: Magnetic resonance imaging.