scholarly journals P665 Which second-line biologic after anti-TNF failure during Crohn’s disease: Ustekinumab or vedolizumab, a multicentre retrospective study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S547-S547 ◽  
Author(s):  
C Rayer ◽  
X Roblin ◽  
D Laharie ◽  
B Caron ◽  
M Flamant ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Risk Model ◽  
Second Line ◽  
Faecal Calprotectin ◽  
Drug Survival ◽  
Cumulative Probabilities

Abstract Background Anti-TNF antibodies treatments are the only first-line reimbursed biologics for Crohn’s disease (CD) in several countries. Recently, Vedolizumab (VDZ) and Ustekinumab (UST) were added to the therapeutic armamentarium for CD refractory to a first anti-TNF antibody. However, studies comparing these two compounds remain unavailable. Our aim was to compare their efficacy in second-line treatment in CD after failure of one TNF antagonist. Methods All patients with CD refractory (primary or secondary non-responders) to first anti-TNF treatment and receiving UST or VDZ as a second biologic were included retrospectively in 10 French tertiary centres. The remission and clinical response were assessed at week 14. On the long-term, the cumulative probabilities of being in remission were estimated using the Kaplan–Meier method and the associated factors using a Cox proportional risk model. The drug survival to assess efficacy as well as side effects was assessed by actuarial analysis. Results 88 patients were included, 50 (57%) females (mean age: 41 ± 15 years), 61 (69%) being treated with UST and 27 (31%) with VDZ. The first anti-TNF was discontinued for primary or secondary non-response in 66 (75%) patients and for side effects in 22 (25%) patients, without any difference between the anti-TNF antibody previously used. Among the 55 patients with endoscopic data at baseline, 55 (98%) had ulceration, a CRP above 5mg/l for 33/71 (46%) patients and a faecal calprotectin > 250 µg/g for the 12 patients tested. At week 14, no difference was observed for clinical response and clinical remission according to the type of treatment: the rate of clinical response and remission were 74% (UST)/58% (VDZ) (p = 0.20) and 33% (UST)/26% (VDZ) (p = 0.56), respectively. The only factor associated with short-term remission was the lack of optimisation prior to anti-TNF discontinuation (p = 0.038) regardless of the type of second-line therapy (UST, p = 0.02; VDZ, p = 0.03). After a mean follow-up of 67 weeks, the cumulative probabilities of being in remission at 6 and 12 months were 16% and 34% for UST and 25% and 44% for VDZ, respectively (p = 0.24 for UST vs. VDZ). The drug survival was higher in the UST group as compared with the VDZ group (HR (UST vs. VDZ) = 2.36 [1.02–5.5], p = 0.04). Conclusion Our preliminary results suggest that VDZ and UST have similar efficacy in the short- and long-term response when used as a second-line biologic therapy in CD refractory to a first anti-TNF antibody. These results will be complemented for the congress by the inclusion of additional patients recruited into this registry.

scholarly journals The Reasons for Discontinuation of Infliximab Treatment in Patients with Crohn's Disease: A Review of Practice at NHS Teaching Hospital

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Lukasz Z. Krupa ◽  
Hugh J. Kennedy ◽  
Crawford P. Jamieson ◽  
Nicola Fisher ◽  
Andrew R. Hart
Keyword(s):  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Maintenance Treatment ◽  
University Hospital ◽  
Infliximab Treatment ◽  
Refractory Disease ◽  
Term Maintenance

Introduction. There is little information on the reasons for discontinuing infliximab treatment in patients with Crohn's disease. The aim of this study was to document these reasons to determine if any were preventable which would allow patients to continue the therapy. Aims & Methods. A review of the medical notes was conducted at the Norfolk and Norwich University Hospital on patients with Crohn's disease treated with infliximab between 2002–2008 to determine the reasons for stopping it. Results. A total of 65 patients were identified who had treatment with infliximab, of whom 23 (35.3%) had their therapy stopped. The reasons for discontinuation of infliximab in the 23 patients were: 47.8% side effects, 17.4% refractory disease, 13.0% achieved remission and did not receive long-term maintenance treatment, 4.34% pregnancy, 4.34% death, and unknown 13.0%. Conclusions. The main reasons for the discontinuation of infliximab were side effects rather than a lack of clinical response.

scholarly journals P389 Efficacy and safety of ustekinumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: real clinical practice

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S400-S401
Author(s):  
R M Saiz Chumillas ◽  
L Alba Hernández ◽  
I Chivato Martín-Falquina ◽  
E Badia Aranda ◽  
M L Arias García ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Real Life ◽  
Corticosteroid Treatment ◽  
Faecal Calprotectin ◽  
Biochemical Remission

Abstract Background The efficacy of ustekinumab in patients with Crohn’s disease (CD) refractory to anti-TNF is worse than in anti-TNF naïve patients. Methods Retrospective study of patients with CD refractory or intolerant to TNF initiating ustekinumab between January 2013 and March 2020, with a minimum follow-up of 12 months, and without corticosteroid treatment. Our aim was evaluated clinical response (reduction of CDAI >100), clinical remission (CDAI <150) and biochemical remission (CDAI <100 and CRP <1 mg/L and faecal calprotectin <100 µg/g) in short and long term. Results A total of 49 patients with a medium follow-up of 28 months (IQR:13-37) were included. Patients baseline characteristics are reflected in Table 1. In 20% patients the induction was made subcutaneous (90 mg/week for 4 weeks). At week 52, clinical response, clinical remission and biochemical remission was 93%, 82% and 54% respectively (Figure 1). In the long term (3 years), 62% had clinical response, 52% remained in clinical remission, and 48% showed biochemical remission. 1/3 of patients needed intensification every year. Ustekinumab treatment discontinuation was observed in 13 patients (27%) mainly due to lack of response (6[12%]: primary, 7[14%]: secondary). No serious adverse effects have been reported. Conclusion About 50% of the patients are in clinical and biochemical remission at week 152 in a real-life cohort of anti-TNF-exposed CD patients. With a harder remission definition including biochemical parameters, our results in real life are similar to pivotal studies at week 152. Nevertheless, at week 52 our remission rates were higher.

scholarly journals P537 Early predictors of long term clinical response to adalimumab in Crohn's disease

2013 ◽  
Vol 7 ◽  
pp. S225-S226
Author(s):  
M. Martinato ◽  
T. Slongo ◽  
M. Piovanello ◽  
M. Rigato ◽  
A. Ugoni ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Early Predictors

scholarly journals P528 Response to biologic therapy in operated Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S454-S454
Author(s):  
A C Georgieva ◽  
A Atanassova ◽  
M Mirchev
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Biological Treatment ◽  
Biological Therapy ◽  
Surgical Intervention ◽  
Mean Value ◽  
Subsequent Treatment ◽  
Time Interval ◽  
Faecal Calprotectin

Abstract Background About 70% of Crohn’s disease (CD) patients undergo surgery due to disease complication. According to the ECCO consensus, in such cases, the tumour necrosis factor-α (TNF-α) antagonists are a means of choice to prevent post-operative relapse. Methods The aim is to evaluate endoscopic, clinical and biochemical outcomes in CD patients, who have undergone surgery, in the course of the subsequent treatment with anti-TNFα mono/combination therapy—anti-TNFα + AZA. Among patients with CD who are undergoing biological treatment, we performed a retrospective analysis of the data of those who underwent surgical intervention associated with Crohn’s disease and subsequently started biological therapy. Results Of the 69 CD patients on biological therapy, surgical intervention was performed in 44.92% (n = 31) of cases prior to the initiation of the treatment. The prevalence of patients with right-sided hemicolectomy with subsequent ileotransverse anastomosis was 54.80%, followed by incision and abscess cavity drainage 22.6%, fistula excision 19.4% and left-sided hemicolectomy 3.2%. In 22 patients (71.0%) there was a clinical response (CDAI decline ≤ 100 points), with 66.66% of them achieving clinical remission (CDAI ≥ 150) (p = 0.001, strong correlation r = 0.596, p = 0.001). During the course of treatment, 23.80% lost clinical response after 18 months of treatment. We compared the mean value of the faecal calprotectin (FCP) before starting, and during the course of the biological treatment, we found that the FCP values decreased 1.5 times: 516.78 ± 273.93, (range 100 – 857)/330.46 ± 432.25, (range 5.32–1800). The activity of the disease measured by CDAI decreases twice during the course of the biological treatment: CDAI 378.00 ± 92.89 (range 258–695)/177.93 ± 116.38 (range 34–414) and CRP values decrease over four times: CRP 59.65 ± 64.52 (range 0.9–225)/13.14 ± 23.59 (range 0.13–116.10). During the course of the biological treatment, intestinal complications were observed in 33.33%, and 9.67% of the patients who had both progression and presence of intestinal complications had a subsequent surgery. In 33.33% of cases, the treatment was intensified. 16.70% of them had to switch to another biological drug. Perianal disease prior to biological treatment in operated patients is twice as common (x2 = 3.82, p = 0.050), which in turn appears to be a risk factor for surgical treatment (OR = 3.47 (0.953–12.685)). Conclusion In the follow up of the relationship between the occurrence of a clinical response and the onset of biological therapy, we found that the time interval was essential. The earlier the anti-TNFα therapy begins, the greater the likelihood of achieving a clinical and biochemical response (r = 0.326, p < 0.05).

scholarly journals P451 Short-and long-term effectiveness of ustekinumab in patients with Crohn’s disease: real-world data from a German IBD cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S405-S405
Author(s):  
A Kubesch ◽  
L Rueter ◽  
K Farrag ◽  
T Krause ◽  
K Stienecker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Treatment Options ◽  
Real World Data ◽  
Free Response ◽  
Faecal Calprotectin ◽  
Short And Long Term

Abstract Background The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, Real-World German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods Patients with CD receiving UST treatment in three hospitals and two outpatient centres were included and retrospectively analysed. Rates for short- and long-term remission and response were analysed with the help of clinical (Harvey–Bradshaw Index [HBI]) and biochemical (C-reactive protein [CRP], faecal calprotectin [fCal]) parameters for disease activity. Results Data from 180 patients were evaluated. One hundred six patients had a follow-up of at least 8 weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin. The median follow-up was 49.1 weeks (95% CI 42.03–56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 39 (41.9%) responded to UST, and 20 patients (21.5%) were in remission. Steroid-free response and remission at week eight were achieved by 30.1%, and 19.3% of patients. At week 48, 26.9% showed steroid-free response to UST, and 15.1% of the initial patient population was in steroid-free remission. Clinical response at week 16 was independently associated with remission at week 48. Conclusion Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment exposed patients.

scholarly journals P329 ECCO grant recipient: preliminary results of the HOT-TOPIC trial (Hyperbaric Oxygen Therapy for the Treatment Of Perianal fistulas In Crohn’s disease)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S318-S319
Author(s):  
C Lansdorp ◽  
K Gecse ◽  
C Buskens ◽  
M Löwenberg ◽  
J Stoker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Hyperbaric Oxygen ◽  
Activity Index ◽  
Perianal Disease ◽  
Faecal Calprotectin ◽  
Preliminary Results ◽  
Patient Reported

Abstract Background Beneficial effects of hyperbaric oxygen (HBO) therapy for perianal fistulising Crohn’s disease (pCD) have been suggested in previous publications. The HOT-TOPIC study was designed to further investigate its feasibility and therapeutic effect in 20 therapy-refractory patients with pCD. Here we present the preliminary results. Methods 17 patients with pCD refractory to conventional-therapy > 6 months (medical and/or surgical, no patients with deviating stoma) were treated with 40 sessions of HBO therapy (243–253 kPa, 110 min per session throughout 8 weeks). Medical treatment remained stable from screening, seton drain(s) were removed after 30 treatment. Co-primary outcomes were clinical response as measured by the perianal disease activity index (PDAI) and MRI improvement measured by the modified van Assche index. Secondary outcomes were clinical response as assessed by fistula drainage assessment (FDA), biochemical response and patient-reported outcomes. All outcomes were assessed at baseline and 2 months after HBO. Results 17 patients (6 female, median age 34 years, median duration of disease 13 years) were treated. Median PDAI scores decreased from 8 to 4 (p < 0.001) and MRI scores from 9.4 to 7.3 (p = 0.001). Defined as PDAI of 4 or less, 11 out of 17 patients had inactive perianal disease after treatment, with 3 patients also having a predominantly fibrotic tract on MRI. Of the 45 external openings draining at baseline, 22 were clinically closed after treatment (49%, assessed by FDA). Four patients, three with one external opening and one with five openings at baseline, had no remaining openings after treatment. Median C-Reactive Protein and faecal calprotectin levels decreased from 5.0 and 416 to 2.3 and 31 (p = 0.002 and p = 0.003), respectively. Median scores of the inflammatory bowel disease questionnaire (IBDQ) increased from 169 to 185 (p = 0.001) and VAS scores from the Euroqol-5-dimensions questionnaire increased from 65 to 75 (p = 0.07), higher scores reflecting better quality of life. When asked on a validated decision regret scale if patients regretted their decision to undergo HBO, the mean score was 12.5 (0–100, higher scores indicating higher regret). During follow-up, none of the patients needed new (experimental) medication, re-interventions or stoma. Seven out of 17 patients experienced trouble equalising middle ear pressure during HBO, with four patients showing signs of barotrauma after otoscopy. Three patients needed tympanostomy tubes. No other clinically relevant adverse events occurred, and no adverse events led to discontinuation of the treatment. Conclusion Based on preliminary data, HBO treatment is associated with significant improvement in pCD, as measured by clinical and MRI endpoints.

Week 6 Calprotectin Best Predicts Likelihood of Long-term Endoscopic Healing in Crohn’s Disease: A Post-hoc Analysis of the UNITI/IM-UNITI Trials

2020 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Predictive Performance ◽  
Drug Level ◽  
Symptom Improvement ◽  
Faecal Calprotectin ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
The Relationship

Abstract Objectives There is need for biomarkers as predictors of outcome of medical treatment in Crohn’s disease. The purpose of this study was to evaluate the predictive performance of faecal calprotectin for short- and long-term clinical and endoscopic outcomes. Methods This post-hoc analysis of the UNITI/IM-UNITI studies [NCT01369329, NCT01369342, and NCT01369355; YODA #2019–4026] included 677 patients to evaluate the relationship of Week 6 calprotectin cut-offs and changes from baseline assessments in calprotectin for prediction of outcomes at Weeks 8, 32, and 52, using receiver operating characteristic curves with comparisons of areas under the curve [AUC]. The relationship between clinical and biomarker assessments at Week 6 and endoscopic remission [ER] at Week 52 was evaluated using multivariate logistic regression models adjusted for confounders. Results A Week 6 calprotectin <250 mg/kg demonstrated a significant ability to predict Week 52 ER (AUC 0.709, 95% confidence interval [CI] 0.566–0.852, p = 0.014) with fair accuracy, and performed better than other calprotectin cut-offs and deltas from baseline for prediction of Week 52 ER. When adjusted for covariates, patients with a Week 6 faecal calprotectin <250 mg/kg had 3.48 times [95% CI 1.31–9.28, p = 0.013] increased odds of Week 52 ER. No other Week 6 clinical assessment [clinical remission or clinical response] or biomarker [CRP <5 or drug level] had an association with Week 52 ER. Conclusions In summary, the results of this post-hoc analysis suggest that Week 6 calprotectin levels < 250 mg/kg can be predictive of future endoscopic healing and may be more informative than clinical symptom improvement. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

scholarly journals P587 Adalimumab in pediatric Crohn’s disease: A long-term multi-centre real-world experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S491-S492
Author(s):  
S Lawrence ◽  
H Huynh ◽  
W El-Matary ◽  
J DeBruyn ◽  
M Carroll ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Long Term Outcomes ◽  
Faecal Calprotectin ◽  
Significant Difference ◽  
Necrosis Factor

Abstract Background There is a paucity of data regarding long-term outcomes for adalimumab (ADA) in pediatric Crohn’s disease (CD). We describe the long-term effectiveness of ADA, in achieving clinical and biochemical remission in a Canadian multi-centre pediatric CD cohort. Moreover, we report the effects of prior anti-TNF exposure and use of a concomitant immunomodulator (IM) on durability of clinical and biochemical response. The primary outcome was 24-month corticosteroid (CS) free remission. Secondary objectives included biochemical and faecal calprotectin response over the study period. Methods Retrospective review of electronic records of all children aged 3–18 years with CD requiring ADA at 4 centres across Canada (Vancouver, Edmonton, Winnipeg and Calgary) between January 2005 and December 2017. Results One hundred and nine children (68% male; median age 13.07 [IQR 10.6–15.1]) with CD (L1 21.7%, L2 28.3%, L3 50%) were included with a median follow-up of 15.9 months [IQR 7.6–24]. Seventy-four patients (67.9%) were anti-tumour necrosis factor (TNF) naïve. Concomitant IM therapy was used in 51 (46.8%). CS free clinical remission at 24 months was observed in 45/66 (68%). Over time, the median PCDAI, CRP, ESR and faecal calprotectin significantly improved (Table 1). During follow-up, 36 (33%) patients discontinued ADA; 6 (5.5%) had primary non-response, 28 (25.7%) had secondary LOR and 2 (1.8%) had intolerance. At 24 months, clinical remission was achieved more frequently in patients who were Anti-TNF naïve (81% vs. 43.5% p 0.002). There was no significant difference in biochemical or faecal calprotectin outcomes between those who were bio-naive or experienced. There was no significant difference in the time to loss of response between those on monotherapy and combination therapy with an IM and ADA (HR 0.64 [95% CI 0.33–1.26] p0.2). Conclusion This study demonstrates that ADA is effective and durable in pediatric CD. Over 24 months, clinical, biochemical and faecal calprotectin improvement was seen. In our cohort, clinical response to ADA was greater in anti-TNF naïve compared with anti-TNF experienced patients; however,, biochemical and faecal calprotectin outcomes did not differ. ADA response appears durable with no significant difference in patients on monotherapy or combination therapy.

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