Introduction

Infliximab (IFX) and vedolizumab (VDZ) are monoclonal antibodies approved for induction and maintenance therapy in inflammatory bowel diseases (IBD). Subcutaneous (SC) formulations of both drugs have recently been approved. However, real-life data are scarce.

Aims & Methods

Our aim was to evaluate the effectiveness of switching from IV to SC formulations of IFX and VDZ in IBD in a real-life setting. This was a multicenter, retrospective, cohort study. All adult patients with moderate to severe Crohn’s disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ were eligible. All available clinical data were collected at 3 and 6 months. Clinical remission was defined as partial Mayo score≤2in UC and Harvey-Bradshaw index (HBI)≤4 in CD. A composite negative endpoint including rate of SC therapy discontinuation, reverse switch from SC to IV drug, need for steroids, and drug optimization was also evaluated at 3 and 6 months. A logistic regression analysis was performed to analyze the association between patients’ characteristics at baseline and the rates of clinical remission at 3 months and composite endpoint at 6 months.

Results

In total, 231 patients (136 UC and 95 CD, 53% male, mean age 44 ± 15 years) from 11 European centers were included in the analysis (Table 1). About two-thirds of patients were treated with IFX (158/231, 68%) while one-third was treated with VDZ (73/231, 32%). The switch occurred at week 6 (after two infusions) in a limited proportion of cases (83/231, 36%). Median time to switch was 13 months (interquartile range 1-61). In total 186/231 (80.5%) of patients were in clinical remission at baseline. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (128/132, 97% and 58/61, 95% respectively) and 6 (123/141, 87% and 43/49, 88% respectively) months after the switch. After 6 months of follow-up, 12 patients (5.2%) underwent reverse switch (7 IFX and 5 VDZ), 9 (3.9%) discontinued therapy (7 IFX and 2 VDZ), 6 (2.6%) required SC drug optimization (4 IFX and 2 VDZ), and 5 (2.2%) required systemic steroids (3 VDZ and 2 IFX). No hospitalization, surgery, dysplasia, or malignancy occurred. In the multivariable analysis, patients with clinical activity at baseline had a lower probability to achieve corticosteroid-free remission at 3 months [odds ratio (OR) 0.04, 95% confidence interval (CI) 0.01-0.16, p< 0.001]. Conversely, duration of IV therapy (OR 0.96, 95% CI 0.94-0.99, p=0.047) and clinical activity at baseline (OR 3.45, 95% CI 1.15-10.31, p=0.026) were independent predictive factors to achieve the negative composite endpoint at 6 months.

	All	Infliximab		Vedolizumab
	231	Crohn’s disease 76	Ulcerative colitis 82	Crohn’s disease 19	Ulcerative colitis 54
Males	122 (52.8%)	41 (53.9%)	49 (59.8%)	4 (21.0%)	28 (51.8%)
Mean age (y) ± SD	43.9 ± 15.0	43.7 ± 15.2	43.8 ± 15.2	44 ± 14.6	44.3 ± 15.1
Disease duration (y) ± SD	12 ± 8.7	11.7 ± 8.8	11.7 ± 8.8	11.7 ± 8.4	11.8 ± 8.6
Disease location L1 ileal L2 colonic L3 ileo-colonic Disease behavior B1 inflammatory B2 stricturing B3 penetrating	39 (41.1%) 14 (14.7%) 42 (44.2%) 44 (46.3%) 33 (34.7%) 18 (19.0%)	30 (39.4%) 13 (17.3%) 33 (42.7%) 34 (44.7%) 28 (36.9%) 14 (18.4%)		9 (47.4%) 1 (5.2%) 9 (47.4%) 10 (52.6%) 5 (26.3%) 4 (21.1%)
Perianal disease	27 (28.4%)	22 (28.9%)		5 (26.3%)
Disease extent E1 proctitis E2 left sided E3 pancolitis	32 (23.6%) 52 (38.2%) 52 (38.2%)		23 (28.0%) 34 (41.5%) 25 (30.5%)		9 (16.7%) 18 (33.3%) 27 (50.0%)
HBI (at baseline) <5 ≥5 pMS (at baseline) ≤2 ≥3	83 (87.4%) 12 (12.6%) 103/136 (75.7%) 33/136 (24.3%)	66 (86.8%) 10 (13.2%)	56/82 (68.3%) 26/82 (31.7%)	17 (89.5%) 2 (10.5%)	47/54 (87.0%) 7/54 (13.0%)
Use of steroids Concomitant (at baseline) Past Use of IMM Concomitant (at baseline) Past Previous use of biologics Never 1 biologic >1 biologic	13 (5.6%) 204 (88.3%) 52 (22.5%) 115 (49.8%) 138 (59.7%) 63 (27.3%) 30 (13.0%)	0 (0.0%) 59 (77.6%) 16 (21,0%) 51 (67.1%) 53 (69.7%) 16 (21.1%) 7 (9.2%)	7 (8.5%) 77 (93.9%) 34 (41.5%) 32 (39.0%) 58 (70.7%) 18 (22.0%) 6 (7.3%)	1 (5.7%) 15 (78.9%) 1 (5.7%) 12 (63.2%) 5 (26.4%) 7 (36.8%) 7 (36.8%)	5 (9.2%) 53 (98.1%) 1 (1.8%) 20 (37.0%) 22 (40.7%) 22 (40.7%) 10 (18.6%)

Conclusion

SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching from IV to SC IFX and VDZ in patients in remission reduces the risk of drug discontinuation, optimization, need for steroids, and reverse switch. Further studies to define the optimal timing to switch from IV to SC drugs are warranted.

Introduction

The risk of postoperative recurrence (POR) within 1 year after ileocecal resection (ICR) for Crohn’s disease (CD) remains high. Currently, there is no consensus on how to optimally reduce the risk of endoscopic (e)POR, clinical (c)POR or surgical (s)POR.

Aims & Methods

The PORCSE study aims to evaluate the impact of two strategies: early medical prophylaxis (proactive strategy) versus treatment driven by findings at elective endoscopy 6-12 months after ICR (reactive strategy).
A retrospective, observational, multicentric, superiority study was performed including CD patients undergoing first ICR between 2008-2019. Patients were assigned to cohort 1 if prophylactic biological or immunomodulator therapy was administered early after ICR, or to cohort 2 if no postoperative prophylaxis was started and medical treatment was driven by endoscopic findings 6-12 months after ICR. The primary endpoint was the rate of ePOR evaluated at ileocolonoscopy 6-12 months post ICR and was defined as Rutgeerts score >i1. Secondary endpoints were colonic disease activity at first endoscopy, severe ePOR (Rutgeerts i3-i4), cPOR (symptoms leading to restart of therapy), sPOR (repeated surgery or endoscopic balloon dilatation) and differences between participating centres.
Statistical analyses were performed with SPSS v28. Propensity score matching was used for regression analyses.

Results

In total 346 patients were included from 26 centres in 9 European countries. Of these, 47.4% received prophylactic postoperative treatment before postoperative endoscopy (cohort 1) and 52.6% did not (cohort 2). Strategy selection differed significantly between countries (P=0.024). The proactive strategy was preferred in Spain and Portugal whereas the reactive strategy in Belgium, France and Ireland. Although not statistically significant (P=0.143), the same trend was noticed in postoperative metronidazole use.
Patients in cohort 1 had more refractory disease with more upper GI disease, more bio-experienced patients, more penetrating disease phenotype and longer disease duration prior to surgery. Furthermore, metronidazole was more frequently started postoperatively in the proactive cohort (31.7%vs14.3%, P<0.001).
Bivariate logistic regression analyses showed significantly higher odds for ePOR in the reactive treatment group (OR 1.809, 95%CI 1.03-3.18, P=0.039). Furthermore, univariate analyses showed higher rates of colonic disease activity in the reactive group at elective endoscopy 6-12 months after surgery. No significant difference in severe ePOR was found at first endoscopy (OR 1.285, 95%CI 0.60-2.74, P=0.517). After first endoscopy until end of follow-up, patients in the reactive group had significantly higher odds of clinical POR (OR 3.047, 95%CI 1.53-6.08, P=0.002). Surgical recurrence rates were numerically higher in the reactive group (OR 2.586, 95%CI 0.995-6.72, P=0.051) and Cox proportional hazards regression analysis showed a trend towards protective effect of the proactive approach (HR 2.497, 95%CI 0.97-6,40, P=0.057).

Table 1: Demographics and POR

Variable	Proactive N=164 (47.4%)	Reactive N=182 (52.6%)	P-value (univariate)	Total (N=346)
Smoking	67 (40.9%)	79 (43.4%)	P=0.057	146 (42.2%)
Montreal classification - +L4 - (p)B3	14 (8.5%) 69 (42.1%)	6 (3.3%) 53 (29.1%)	P=0.037 P=0.012	20 (5.8%) 122 (35.3%)
Preoperative immunomodulator	124 (75.6%)	97 (53.3%)	P<0.001	221 (63.9%)
Preoperative biologic	98 (59.8%)	78 (42.9%)	P=0.001	176 (50.9%)
Biochemical inflammation* and/or steroid use <4 weeks prior to surgery	101 (61.6%)	89 (48.9%)	P=0.018	190 (54.9%)
ePOR (Rutgeerts >i1)	68 (41.5%)	98 (53.8%)	P=0.021	166 (48.0%)
Colonic endoscopic activity	30 (18.3%)	47 (25.8%)	P=0.032	77 (33.5%)
cPOR	29 (17.7%)	65 (35.7%)	P<0.001	94 (27.2%)
sPOR	11 (6.7%)	24 (13.2%)	P=0.046	35 (10.1%)

* CRP>10mg/L or fecal calprotectin ³250mcg/g

Conclusion

The retrospective PORCSE study provides evidence to support a proactive approach over a reactive approach in terms of prevention of not only endoscopic but also clinical and surgical postoperative recurrence after first ileocecal resection for Crohn’s disease.

Disclosure

Authors have nothing to disclose related to this project

Introduction

In patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous (IV) steroids, the most effective treatment regimen is unknown. The benefit of early infliximab (IFX) therapy remains to be established in this indication.

Aims & Methods

In this French multicentre, parallel group, open-label randomised controlled trial, thiopurine and biologics-naïve adults admitted for ASUC defined by a Lichtiger score >10 were included between December 2016 and June 2021 if they responded to IV steroids. Response to IV steroids was defined according to the absence of Oxford criteria. They were randomly assigned to receive an early combination therapy with IFX (5 mg/kg IV at week 0, 2 and 6 and then every 8 weeks) and azathioprine (AZA) (2 and 2.5 mg/kg/day) with a quick steroid discontinuation of AZA (2 and 2.5 mg/kg/day) and standardized steroid tapering regimen (AZA arm). Steroids use was prohibited after day 7 in the IFX+AZA arm and after week 14 in the AZA arm.
The primary endpoint was treatment failure at week 52 (w52), defined as absence of steroid-free clinical remission according to total Mayo Clinic score (≤2 with no individual subscore >1) at w52, absence of endoscopic response (Mayo endoscopic subscore of 0 or 1 according to local reading) at w52, or use of a prohibited treatment for relapse (partial Mayo score >5), severe adverse event leading to interruption of any of the allocated treatment, colectomy or death during the study period.
A sample size of 73 patients per group was calculated to detect 24%-difference between both group with a 1:1 randomization ratio, a 80% power and a 5% two-sided alpha risk. Due to challenges in recruiting patient, the steering committee decided to prematurely terminate the study in September 2019 blindly of any study results, after including 64 patients.

Results

64 were randomised (32 males, median age of 34.5 [IQR 26.3-50.3] years, 38% with pancolitis, Lichtiger score of 13.0 [95%CI 12-14], CRP of 29.0 [12.8-96.8] mg/L and serum albumin of 31.2 [27.7-35.6] g/L at baseline): 32 were assigned to IFX+AZA arm and 32 to AZA arm. Components of the composite primary endpoint are given in table 1.

	IFX + AZA arm (n=32)	AZA arm (n=32)
Death	0	0
Colectomy	0	0
use of a prohibited treatment for relapse	6 (18.8%)	10 (31.2%)
severe adverse event leading to interruption of any of the allocated treatment	5 (15.6%)	3 (9.4%)
Retracted consent	1 (3.1%)	0
Absence of steroid-free clinical remission at w52	5 (15.6%)	8 (25.0%)
Mayo endoscopic subscore ≥2	6 (18.8%)	8 (25.0%)

In the ITT population, treatment failure at w52 was observed in 81.5% in the AZA arm versus 53.3% in the IFX+AZA arm (OR 3.85, 95%CI [1.15-12.88], p=0.03). In the PP population, treatment failure at week 52 was observed in 81.5% (22/27) in the AZA arm versus 50.0% (13/26) in the IFX + AZA arm (OR 4.40, 95%CI [1.28-15.18], p=0.02). In total 121 treatment emergent adverse events (AE) were reported in 40 patients including 23 serious AE in 18 patients (11 in the IFX + AZA arm vs 7 in the AZA arm, p=0.24). Serious AE included infectious AE in 6 cases (1 vs 5, p=0.20) and UC relapse in 9 (4 vs 5, p=0.60). No deaths were reported.

Conclusion

At w52, combination therapy with IFX + AZA and quick steroids discontinuation was more effective than AZA with standard steroids tapering regimen to prevent treatment failure in patients with ASUC responding to IV steroids. In routine practice, pre-emptive use of early combination therapy with IFX + AZA should be encouraged in ASUC patients responding to IV steroids (EudraCT 2014-005212-42).

Disclosure

this study was funded by Pfizer