P402 Normalized wall thickness at MRE predicts clinical remission in Crohn's disease after infliximab discontinuation: a 5 years follow-up

Abstract Background Stricturing Crohn’s disease (CD) constitutes a severe phenotype often associated with a high degree of morbidity (3). Surgical resection is first-line therapy for symptomatic strictures, but most patients relapse without subsequent medical therapy (4–5). Biologics are the mainstay for inducing and maintaining remission, but some cases are refractory despite maximum dosage of therapy. Reports of dual biological therapy (DBT) in refractory, stricturing CD are sparse, and prior case reports document only clinical remission (1). To contribute further knowledge regarding the use of DBT in stricturing CD, we present the case of a refractory CD patient who achieved deep remission with ustekinumab and vedolizumab. Case Presentation A 35 year old non-smoking, Caucasian male was referred to our clinic in 2014 for refractory CD complicated by multiple strictures. Prior to establishing care with us, he received two jejunal resections and a sigmoid resection. Previously failed therapies included azathioprine with infliximab, adalimumab, and certolizumab. He continued to progress under our care despite combination methotrexate/certolizumab, as well as methotrexate/golimumab. He underwent proctocolectomy with end ileostomy in 2015 and initiated vedolizumab q8weeks post-operatively. He reoccurred in 2018, when he presented with an ulcerated ileal stricture. He was switched from vedolizumab to ustekinumab q8weeks and placed on prednisone, but continued to progress, developing significant hematochezia requiring hospitalization and blood transfusions. Ileoscopy performed during hospital admission confirmed severe, ulcerating disease in the ileum with stricture. Ustekinumab dosing was increased to q4weeks, azathioprine was initiated, and he underwent stricturoplasty. Follow-up ileoscopy three months later revealed two ulcers in the neo- TI (Figure 1). Vedolizumab q8weeks was initiated in addition to ustekinumab q4weeks and azathioprine 125mg. After four months on this regimen the patient felt better, but follow-up ileoscopy showed two persistent ulcers in the neo-TI. Vedolizumab dosing interval was increased to q4weeks. After four months, subsequent ileoscopy demonstrated normal neo-TI (Figure 2). Histologic evaluation of biopsies confirmed deep remission of crohn’s disease. No adverse side effects have occurred with maximum doses of both ustekinumab and vedolizumab combination therapy. Discussion This case supports both the safety and efficacy of ustekinumab and vedolizumab dual biologic therapy for treatment of severe, refractory Crohn’s disease. While there are reports of DBT inducing clinical remission, this case supports efficacy for vedolizumab and ustekinumab combination therapy to induce deep histologic remission. Large practical clinical trials are needed to better investigate the safety and efficacy of DBT with vedolizumab and ustekinumab, but our case suggests this combination may be a safe and efficacious therapy for refractory CD patients.

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P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.187 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S75-S75

Author(s):

Scott D Lee ◽

Anand Singla ◽

Caitlin Kerwin ◽

Kindra Clark-Snustad

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Events ◽

Real World ◽

Clinical Remission ◽

Mucosal Healing ◽

Clinical Disease ◽

Endoscopic Remission ◽

Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with >3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

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Sa1194 Prospective, Multicenter Capsule Endoscopy Study of Small Bowel Crohn's Disease Patients in Clinical Remission: Long-Term Follow-Up and Correlation With Faecal Lactoferrin and Calprotectin Levels

Gastroenterology ◽

10.1016/s0016-5085(14)60798-8 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-225-S-226

Author(s):

Vipul Aggarwal ◽

Andrew S. Day ◽

Susan J. Connor ◽

Steven T. Leach ◽

Gregor J. Brown ◽

...

Keyword(s):

Crohn’S Disease ◽

Small Bowel ◽

Crohn's Disease ◽

Capsule Endoscopy ◽

Clinical Remission ◽

Long Term Follow Up

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P286 Ustekinumab for Crohn’s Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.411 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S319-S320

Author(s):

T Straatmijer ◽

V B C Biemans ◽

F Hoentjen ◽

N K H de Boer ◽

A G Bodelier ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Real World ◽

Clinical Remission ◽

Prospective Cohort ◽

Upper Airway ◽

Fecal Calprotectin ◽

Regular Care ◽

Observational Cohort

Abstract Background Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin (IL)-12 and IL-23. It is registered for the treatment of Crohn’s disease (CD) and ulcerative colitis. We assessed the two-year efficacy and safety of ustekinumab in a real world, prospective cohort of CD patients. Methods CD patients who started ustekinumab in regular care were prospectively enrolled in the nationwide Initiative on Crohn and Colitis Registry. At week 0, 12, 24, 52 and 104, clinical remission (HBI ≤ 4 points), biochemical remission (fecal calprotectin (FC) ≤200 μg/g and/or CRP ≤5 mg/L), peri-anal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. Patients starting therapy less than two years ago were excluded for the current evaluation. The primary outcome was corticosteroid-free clinical remission at week 104. Results In total, 252 CD patient with at least two years of follow up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission at week 12, 24, 52 and 104 was 32.3% (81/251), 41.4% (104/251), 39% (97/249) and 34.0% (84/247), respectively. Of the 97 patients in corticosteroid free clinical remission at week 52, 58 (59.8%) were still in corticosteroid-free clinical remission at week 104. In patients with combined clinical and biochemical disease activity at baseline (n=122), the corticosteroid-free clinical remission rates were 23.8% (29/122), 35.2% (43/122), 40.0% (48/120) and 32.8% (39/119) at week 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks was 64.3% and 54.8%, respectively. There were no predictive factors associated with corticosteroid-free clinical remission at week 104 on univariate and multivariate analysis. Most common adverse events were headache, skin reaction and musculoskeletal complaints. Two patients stopped ustekinumab due to an infection after 8 and 30 weeks of treatment (mild fever syndrome and moderate upper airway infection, respectively). The main reason for discontinuing treatment after 52 weeks was loss of response (66.7%). Conclusion Ustekinumab was effective and relatively safe in our real world, prospective cohort of CD patients. After 104 weeks of ustekinumab treatment, one third of patients were in corticosteroid-free clinical remission.

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P568 Effectiveness of ustekinumab after vedolizumab failure in patients with anti-TNF-refractory Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.689 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S528-S528

Author(s):

N Dussias ◽

F Rizzello ◽

C Calabrese ◽

A Sanna Passino ◽

L Melotti ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Partial Response ◽

Clinical Remission ◽

Primary Outcome ◽

Symptom Control ◽

Primary Outcome Measure ◽

Referral Centre ◽

Single Centre Study

Abstract Background Both vedolizumab (VDZ) and ustekinumab (UST) are indicated in the treatment of Crohn’s disease (CD) when anti-TNF treatment fails. While there are some studies regarding the efficacy of these two drugs in this setting, data are lacking regarding the effectiveness of UST in the treatment of VDZ-refractory disease. We aim to address this particularly challenging clinical picture in a real-world single-centre study. Methods CD patients from a single tertiary IBD referral centre receiving treatment with UST after failure to VDZ with a minimum follow-up period of 6 months were included. All patients had previously failed anti-TNF treatment. The primary outcome measure was achievement of steroid-free clinical remission, defined as HBI < 5 at 6 months. We also assessed rates of partial response, defined as a reduction in HBI by ≥ 3 points and/or cessation of steroid treatment in patients who required corticosteroids at baseline for symptom control. Results A total of 32 patients (20 male, mean age ± SD 40.7 ± 14.2, range 21–75) receiving UST treatment after VDZ failure were analysed. Complete steroid-free clinical remission at 6 months from starting UST therapy was achieved in 19 patients (59.4%). Nine patients (28.1%) had partial response, while in the remaining 4 patients (12.5%) no response was achieved. No adverse events were recorded during the follow-up period. Conclusion Preliminary results suggest that UST is effective and safe in the treatment of VDZ-refractory CD.

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A228 EVOLUTION OF MRE FINDINGS IN PAEDIATRIC PATIENTS WITH SMALL BOWEL CROHN’S DISEASE ON MAINTENANCE METHOTREXATE

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.227 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 103-104

Author(s):

A Kellar ◽

N Carmen ◽

M Greer ◽

T Walters ◽

A Griffiths ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Remission ◽

Global Assessment ◽

Activity Index ◽

Severe Disease ◽

Clinical Findings ◽

Mild Disease ◽

Surgical History

Abstract Background Observational data in children and RCT data in adults indicate that methotrexate (MTX) is associated with induction and maintenance of clinical remission in luminal Crohn’s disease, but efficacy in achieving intestinal healing has not been examined. Aims To examine the evolution of MRE signs of inflammation in children treated with MTX. Methods In this retrospective cohort study, we reviewed paediatric CD patients on maintenance MTX monotherapy for >4 months who underwent serial MREs between July 2010 and October 2015. MREs were reviewed by a radiologist blind to clinical data. Overall inflammatory activity on each MRE was scored as minimal, mild, moderate or severe, informed by the presence of bowel wall thickness, wall enhancement, T2 hyperintensity, comb sign, mesenteric edema, penetrating disease, stricturing, diffusion restriction and motility. The radiologist’s global assessment of change from MRE 1 to MRE 2 was scored as improved, unchanged or worsened. Clinical findings, disease activity (assessed by weighted paediatric CD activity index [wPCDAI]) and surgical history were also extracted from medical records by a clinician blind to MRE results. Results Thirty-five patients were included (median age at diagnosis 12 [IQR 11–14] years; 77% male; 60% inflammatory (B1), 17% stricturing (B2), 23% penetrating (B3) disease). Between baseline and follow-up MRE, wPCDAI (median 15 [IQR 7–43] decreased to 8 [IQR 0–18]; p=0.006) and CRP (median 9 [IQR 2–36] decreased to 5 [IQR 5–9]; p=0.013) and 74% (N=26) were in clinical remission (wPCDAI < 12.5) at MRE 2. MRE features that significantly improved from MRE 1 to 2 were comb sign from 63% (N=37) to 38% (N=14) (p=0.02) and penetrating disease from 14% (N=8) to 0 (p=0.03). After a median of 17 months (IQR 13–23), 51% (N=18) of patients improved, 29% (N=10) worsened and 20% (N=7) had no change based on the radiologist’s global assessment. Of the 21 patients with moderate/severe disease at MRE 1, 33% (N=7) had minimal/mild disease by MRE 2. 66% (N=14/21) continued to have moderate/severe disease at MRE 2. Additionally, a further 14% (N=2/14) of those with minimal/mild disease at baseline MRE progressed to moderate/severe disease at MRE 2. Complete details of change between MRE 1 and MRE 2 are displayed in Figure 1. Conclusions Despite signs of clinical improvement, many paediatric CD patients on maintenance MTX therapy for >4 months have unchanged or worsened MRE findings. This underscores the need for follow-up imaging in these cases. Funding Agencies None

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Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa177 ◽

2020 ◽

Author(s):

Mathurin Fumery ◽

Laurent Peyrin-Biroulet ◽

Stephane Nancey ◽

Romain Altwegg ◽

Cyrielle Gilletta ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Events ◽

Multicentre Study ◽

Clinical Remission ◽

Intestinal Resection ◽

Serious Adverse Events ◽

Faecal Calprotectin ◽

Loss Of Response

Abstract Background The approved maintenance regimens for ustekinumab in Crohn’s disease [CD] are 90 mg every 8 or 12 weeks. Some patients will respond partially to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections. Methods All patients with active CD, as defined by Harvey–Bradshaw score ≥ 4 and one objective sign of inflammation [C-reactive protein > 5 mg/L and/or faecal calprotectin > 250 µg/g and/or radiological and/or endoscopic evidence of disease activity] who required ustekinumab dose escalation to 90 mg every 4 weeks for loss of response or incomplete response to ustekinumab 90 mg every 8 weeks were included in this retrospective multicentre cohort study. Results One hundred patients, with a median age of 35 years [interquartile range, 28–49] and median disease duration of 12 [7–20] years were included. Dose intensification was performed after a median of 5.0 [2.8–9.0] months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 [1.3–3.0] months. After a median follow-up of 8.2 [5.6–12.4] months, 61% of patients were still treated with ustekinumab, and 26% were in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission [no ulcers]. At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicentre study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.

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DOP80 Effectiveness of ustekinumab and vedolizumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: A multi-centre comparative study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.119 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S118-S120 ◽

Cited By ~ 1

Author(s):

H Alric ◽

A Amiot ◽

J Kirchgesner ◽

X Tréton ◽

M Allez ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Remission ◽

Propensity Scores ◽

Remission Rate ◽

University Hospitals ◽

Clinical Remission Rate ◽

Paris Area ◽

History Of

Abstract Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn’s disease (CD) refractory to anti-TNF. In France between May 2014 and November 2016, vedolizumab (and not ustekinumab) was reimbursed for patients who had failed anti-TNF. Then, between December 2016 and August 2018, ustekinumab (and not vedolizumab) was reimbursed for this category of patients. Since September 2018, both ustekinumab and vedolizumab are reimbursed in patients who are refractory to anti-TNF. The aim of this study was to compare effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF. Methods We studied all consecutive patients with active CD who were refractory to at least one anti-TNF, and were treated either with vedolizumab or ustekinumab, in five university hospitals of the Paris area, between May 2014 and August 2018. The primary endpoint was clinical remission rate at week 48. Adjustment according to propensity scores with inverse probability of treatment weighting was performed. Results 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. After propensity scoring with IPTW, there was no difference between the two groups (Figure 1). At week 48, the clinical remission rate was higher with ustekinumab than with vedolizumab (54.4% vs. 38.3%; OR =1.92, 95% CI [1.09–3.39]). At week 48, corticosteroid-free remission rate tended to be numerically higher with ustekinumab than with vedolizumab (44.7% vs. 34.0%; OR = 1.57, 95% CI [0.88–2.79]). Treatment persistence was significantly more frequent in the ustekinumab group (71.5% vs. 49.7%; OR = 2.54, 95% CI [1.40–4.62]). The dose optimisation rate at week 48 was higher with vedolizumab than with ustekinumab (53.5% vs. 30.1%; OR = 0.37, 95% Cl [0.21–0.67]). Subgroup analyses showed that ustekinumab was associated with higher clinical remission rates at week 48 in patients with ileal CD (OR = 3.49; 95% CI [1.33–9.17]), a penetrating phenotype (OR = 6.58; 95% CI [1.91–22.68]) and a history of perianal disease (OR = 2.48; 95% CI [1.04–5.93]). Regardless of treatment group, combotherapy was associated with a higher clinical remission rate at week 48 (OR = 1.93; 95% CI [1.09–3.43]). Conclusion This study suggests that, after 1 year of follow-up, ustekinumab is associated with a higher rate of clinical remission than vedolizumab in CD patients refractory to anti-TNF, particularly in those with ileal and penetrating disease.

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