P445 Does The Sequence Matter ? Comparative effectiveness of a second line biologic in patients with Ulcerative Colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

Abstract

Background
Drug choice and order in Inflammatory Bowel Disease (IBD) is an important challenge and is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second line treatments in Ulcerative Colitis (UC). It is unclear if using anti-Tumour Necrosis Factor-a (anti-TNF) therapy following vedolizumab (VDZ) or VDZ after anti-TNF has a more favourable outcome in UC in a real-world outpatient setting.

Methods
Patients with UC who were exposed to first-line anti-TNF (adalimumab/ADA or infliximab/IFX) or VDZ who subsequently switched to the alternate class between May 2013-August 2020 were identified following a review of databases at 10 hospitals. 88 VDZ and 39 anti-TNF (12 ADA,27 IFX) second line patients were eligible. Data was collected retrospectively. Baseline demographics, disease activity indices, colectomy rates, treatment persistence and healthcare resource utilisation composite endpoint (HRUC) were examined over a 52 week period for the second line biologic. HRUC included unplanned emergency hospital attendance or hospital admission.
The primary endpoints of 52 week treatment persistence, HRUC survival and colectomy free survival were analysed with Kaplan Meier method, statistical significance between the survival curves was assessed with Log Rank test. Propensity score matching (PSM) was applied to survival curves (tolerance level 0.1). For a subset where SCCAI scores available, week 52 corticosteroid free clinical response/remission rates were calculated (response: reduction of SCCAI ≥3 and remission: SCCAI ≤2).:

Results
The second line anti-TNF group had a significantly higher baseline endoscopic Mayo score (p=0.035) and lower concomitant immunomodulator use (p=0.001). Second line week 52 treatment persistence was higher in the VDZ group 71/80 (89%) vs. Anti-TNF 15/36 (42%) ,p<0.0001 (Figure 1). Second line week 52 HRUC survival was higher in the VDZ group 68/81 (84%) vs. anti-TNF 20/33 (61%), p=0.003 (Figure 2). Week 52 colectomy free survival VDZ 77/80 (96%) vs. anti-TNF 26/32 (81%), p= <0.011 (Figure 3). For treatment persistence and colectomy free survival statistical significance was maintained with PSM. Week 52 corticosteroid free clinical remission rates VDZ 22/32 (69%) vs. anti-TNF 5/19 (25%) p=0.004 (Figure 4).

Conclusion
The VDZ second line cohort had significantly higher 52-week treatment persistence, lower HRUC and lower colectomy rates and higher corticosteroid free clinical remission rates. This data suggests that VDZ is an effective biologic in UC in a second line therapy after anti-TNF exposure. It highlights the effect of biologic sequencing on clinically important outcomes in an outpatient setting. Larger prospective studies are required to confirm these findings.

Full text

Abstracts of the 16th Congress of ECCO - European Crohn's and Colitis Organisation S443
Results: Out of 63 patients, mean age 13.6 (±3) years, females
28(44.4%),54 (85.7%) had Crohn’s disease. The median (interquar-
tile range) FC at baseline was 715µgr/gr (312–1700). The outcomes
of <250, <150, <100 and <50µgr/gr were achieved by 52 (82%), 51
(81%), 44 (70%) and 32 (50%) patients, respectively. The mean time
(± standard error) for achieving these cut-offs were 4.8±0.8, 7.9±1.3,
10±1.8 and 18.5±7.2 months, respectively. There was no statistic-
ally signicant correlation between age, gender, type of disease, Paris
classication, extra-intestinal manifestation, albumin levels, erythro-
cyte sedimentation rate, C-reactive protein and the pediatric disease
activity indexes at baseline and FC response. Furthermore, there was
no statistically signicant correlation between anti TNFα trough
concentration during induction and FC response.
Conclusion: In pediatric patients with IBD, FC response (<250µgr/
gr) was achieved by the majority of patients within a relatively short
period of time. Nevertheless, calprotectin normalization (<100µgr/gr)
required an average period of approximately one year in responders.
P445
Does The Sequence Matter ? Comparative
effectiveness of a second line biologic in patients
with Ulcerative Colitis: vedolizumab followed
by an anti-TNF versus anti-TNF followed by
vedolizumab
C.Miller*1, H.Kwok1, I.Parisi1, P.  Harrow1, S.McCartney1,
R.Vega1, F.  Rahman1, E.Seward1, S.Mehta1, S.Lim2, E.Sharma2,
M.Samaan2, A.Bancil3, K.Kok3, A.Shalabi4, E.Johnston4,
D.Katarey5, N.Taherzadeh5, C.Murray5, M.Sharip6, M.Carter6,
S.Radhakrishnan7, S.Peake7, I.Khakoo8, M.Wahed8, S.Povlsen9,
M.Patel9, P. Dubois9, J.Finkel10, C.Onnie10, S.Bloom1
1University College Hospital, Gastroenterology Department, London,
United Kingdom, 2Guy’s and Thomas’ Hospital, Gastroenterology
Department, London, United Kingdom, 3Royal London Hospital,
Gastroenterology Department, London, United Kingdom, 4West
Middlesex Hospital, Gastroenterology Department, London, United
Kingdom, 5Royal Free Hospital, Gastroenterology Department,
London, United Kingdom, 6Lister Hospital, Gastroenterology
Department, Stevenage, United Kingdom, 7St Mary’s Hospital,
Gastroenterology Department, London, United Kingdom, 8Chelsea
and Westminster Hospital, Gastroenterology Department, London,
United Kingdom, 9King’s College Hospital, Gastroenterology
Department, London, United Kingdom, 10Whittington Hospital,
Gastroenterology Department, London, United Kingdom
Background: Drug choice and order in Inammatory Bowel Disease
(IBD) is an important challenge and is becoming increasingly
complex. There are few studies comparing head-to-head outcomes
in second line treatments in Ulcerative Colitis (UC). It is unclear if
using anti-Tumour Necrosis Factor-a (anti-TNF) therapy following
vedolizumab (VDZ) or VDZ after anti-TNF has a more favourable
outcome in UC in a real-world outpatient setting.
Methods: Patients with UC who were exposed to rst-line anti-TNF
(adalimumab/ADA or iniximab/IFX) or VDZ who subsequently
switched to the alternate class between May 2013-August 2020
were identied following a review of databases at 10 hospitals. 88
VDZ and 39 anti-TNF (12 ADA,27 IFX) second line patients were
eligible. Data was collected retrospectively. Baseline demographics,
disease activity indices, colectomy rates, treatment persistence and
healthcare resource utilisation composite endpoint (HRUC) were
examined over a 52 week period for the second line biologic. HRUC
included unplanned emergency hospital attendance or hospital
admission.
The primary endpoints of 52 week treatment persistence, HRUC
survival and colectomy free survival were analysed with Kaplan
Meier method, statistical signicance between the survival curves
was assessed with Log Rank test. Propensity score matching (PSM)
was applied to survival curves (tolerance level 0.1). For a subset
where SCCAI scores available, week 52 corticosteroid free clinical
response/remission rates were calculated (response: reduction of
SCCAI ≥3 and remission: SCCAI ≤2).:
Results: The second line anti-TNF group had a signicantly higher
baseline endoscopic Mayo score (p=0.035) and lower concomitant
immunomodulator use (p=0.001). Second line week 52 treatment
persistence was higher in the VDZ group 71/80 (89%) vs. Anti-TNF
15/36 (42%) ,p<0.0001 (Figure 1). Second line week 52 HRUC sur-
vival was higher in the VDZ group 68/81 (84%) vs. anti-TNF 20/33
(61%), p=0.003 (Figure 2). Week 52 colectomy free survival VDZ
77/80 (96%) vs. anti-TNF 26/32 (81%), p= <0.011 (Figure 3). For
treatment persistence and colectomy free survival statistical signi-
cance was maintained with PSM. Week 52 corticosteroid free clinical
remission rates VDZ 22/32 (69%) vs. anti-TNF 5/19 (25%) p=0.004
(Figure4).
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S444 Poster presentations
Conclusion: The VDZ second line cohort had signicantly higher
52-week treatment persistence, lower HRUC and lower colectomy
rates and higher corticosteroid free clinical remission rates. This data
suggests that VDZ is an effective biologic in UC in a second line
therapy after anti-TNF exposure. It highlights the effect of biologic
sequencing on clinically important outcomes in an outpatient setting.
Larger prospective studies are required to conrm these ndings.
P446
Plasma rich in growing factors as treatment for
perianal fistulas in Crohn’s disease: unicentre
experience.
A.SotoSánchez1, A.HernandezCamba*2, M.Hernández1,
G.Hernández1, E.PérezSánchez1, M.BarreraGómez1
1Hosp. Universitario Nuestra Señora de la Candelaria, Department
of Surgery, Santa Cruz de Tenerife, Spain, 2Hosp. Universitario
Nuestra Señora de la Candelaria, Department of Gastroenterology,
Santa Cruz de Tenerife, Spain
Background: Perianal Crohn’s disease (PCD) adds a signicant mor-
bidity and reduced quality of life. Complex stulas occur in up to
20% of patients. The available treatment of PCD includes immuno-
suppressive drugs, antibiotics, different surgeries but are associated
with high recurrence rates. Anew alternative using plasma rich in
growth factors (PRGF) for the treatment of complex stulas has
emerged from to achieve better healing with the minimum possible
complications without affecting anal continence. This study aims to
assess the feasibility, safety and efcacy of local injection of PRGF
in patients with PCD.
Methods: Retrospective observational and descriptive study analyz-
ing 6 Crohn´s Disease (CD) patients undergoing complex anal s-
tula sealing with PRGF from March 2019 to December 2020. All
patients underwent endoanal ultrasound and 60% a pelvic mag-
netic resonance also. The technique consisted of locating the tract
without the use of hydrogen peroxide, active curettage of the tract
and closure the internal stulous orice (IFO) with single stitches
Vicryl® 3/0. Subsequently, 50% of the PRGF-rich fraction was
injected in the submucosa of the closed internal stula orice. The
other 50% is injected in the stulous tract. With PRGF-poor fraction
a three-dimensional brin matrix is created and lled the previously
curetted stulous tract. We describe the results in terms of demo-
graphic variables, outcomes, surgical procedure and complications.
Endpoint was stula closure by physical examination and endoanal
ultrasound.
Results: Sixty seven percent of the patients were female, mean age
was 43 (26y SD). The clinical characteristics of the patients are
described in table1. All of the patients had previous abscess drain-
age surgery. The most frequent stula was mid-transsphincteric
type. 66.7% had seton at the time of surgery and only one patient
had no medical treatment at that time. The median follow-up was
30months. The recurrence rate was 66.7% with no differences with
in age, sex, comorbidity, type of stula, stula location, medical
treatment and whether they had a seton implanted at the time of
surgery. No patient presented complications. The median follow-up
was 16months.
Conclusion: PRGF sealing appears to be feasible, safe and a promis-
ing option in the treatment of PCD. Further studies should be carried
out to determine the real use of PRGF in PCD.
P447
Combined fibrin glue with infliximab therapy
of postoperative anastomotic fistula in patients
with Crohn’s disease: APilot study
Y.  Li*1, D. Yao1
1Shanghai Ninth People’s Hospital -Shanghai Jiaotong University
School, Department of Surgery, Shanghai, China
Background: Postoperative anastomotic stula is one of the most
frequent and potentially life-threatening complications following
gastrointestinal resections in patients with Crohn’s disease. The pur-
pose of this study was to report the results of iniximab promoting
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