scholarly journals P362 Prospective study of phArmaCokinetics of InFliximab during induction in patients with Crohn’s disease and ulcerative colitis (PACIFIC)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S343-S344
Author(s):  
C Liefferinckx ◽  
P Bossuyt ◽  
D Thomas ◽  
J F Rahier ◽  
E Louis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Prospective Study ◽  
Clinical Remission ◽  
Drug Level ◽  
Individual Variability ◽  
Sustained Remission ◽  
Faecal Calprotectin ◽  
Affinity Capture

Abstract Background Loss of response (LOR) to infliximab (IFX) remains a challenge in routine management of IBD patients. We evaluated IFX high-resolution pharmacokinetics (PK) during induction with intermediate and peak PK levels. Methods This is a prospective, multicentre (n = 9), interventional study approved by EC (P2017/484). Fourteen blood samples were collected per patient from baseline to week 30. All patients were IFX naïve with active disease according to clinical, biological and endoscopy criteria. The primary outcome evaluated the inter-individual variability of IFX PK during induction and correlation with remission at week 30. In addition to trough levels (TLs), intermediate (ILs) and peak levels (PLs) were also measured and defined as drug level between two infusions and drug level early on after infusion (+2h), respectively. Remission was defined as having a Harvey Bradshaw Index (HBI) ≤ 4 and C-Reactive Protein (CRP) ≤5 for Crohn’s disease (CD), and as a clinical Mayo score ≤2 and faecal calprotectin <250 µg/g for ulcerative colitis (UC). IFX samples were measured by ELISA (Apdia) while a drug-tolerant affinity capture elution anti-infliximab assay was used to measure anti-infliximab antibodies (ATI) at weeks 6, 22 and 30. Results Demographic and baseline data of the study population are presented in Table 1. Among the 62 patients enrolled, 33.9% of patients (n = 21/62) were in remission at week 30. Eight patients dropped out due to disease worsening. Median TLs at week 6 were higher among patients in clinical remission at week 30 (p = 0.02) confirming previous observations. However, ILs at day 3 as well as PLs after the third infusion were also significantly higher in patients in clinical remission at week 30 (Figure 1a–c). ATI were detected as soon as week 6. At week 2, infliximab levels were significantly lower among patients in which ATI developed at a later time point (p = 0.006) and this observation was confirmed when measuring ILs at day 17 (p = 0.002), TLs at week 6 (p = 0.002) and ILs at week 10 (p = 0.001). Conclusion This multicentre prospective study demonstrates that intermediate levels as early as day 3 predict remission at week 30 in IBD patients. Low IFX levels during induction were correlated to future ATI development. PK modelling may allow to better select patients early on for sustained remission with infliximab.

scholarly journals DOP67 Comparison of the pharmacokinetics of CT-P13 between Crohn’s Disease and Ulcerative Colitis in biologic-naïve patients; a prospective multi-center observational study of the KASID

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S101-S102
Author(s):  
E S Kim ◽  
D I Park ◽  
H J Kim ◽  
Y J Lee ◽  
J S Koo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Observational Study ◽  
Clinical Outcomes ◽  
Clinical Remission ◽  
Repeated Measures ◽  
Hazard Analysis ◽  
Drug Level ◽  
Intention To Treat

Abstract Background We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes. Methods This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose. Results 267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p<0.001) and clinical response (75.6% vs. 47.5%, p<0.001) at 54-week were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to 14-week (2-week, 19 vs. 15, p<0.001; 6-week, 13 vs. 9, p<0.001; 14-week, 3 vs. 2, p=0.001, Fig 1). The median ADA level (AU/mL) was significantly lower in CD than in UC at 2-week (6 vs. 7, p=0.046), 30-week (8 vs. 12, p=0.007) and 54-week (9 vs. 12, p=0.032, Fig 1). The difference in drug and ADA levels between CD and UC remained significant after adjustment for confounders in repeated measures analysis. Cox proportional hazard analysis showed that CD over UC (adjusted hazard ratio (aHR) 0.78, 95% confidence interval (CI) 0.62–0.95, p=0.016, Fig 2) and no immunomodulator (aHR 1.55, 95% CI 1.07–2.25, p=0.02) were independent risk factors for the development of ADA. The development of ADA at 2-week (adjusted odds ratio (aOR) 0.12, 95% CI 0.03–0.6, p=0.009) and CD over UC (aOR 1.85, 95% CI 1.33–2.56, p=0.0002) were independent predictors of clinical remission at 54-week. Conclusion CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.

M1234 Faecal Calprotectin Cannot Predict Early Crohn's Disease Relapse in Infliximab Responders: A Prospective Study

2010 ◽  
Vol 138 (5) ◽  
pp. S-360
Author(s):  
David Laharie ◽  
Samir Mesli ◽  
Farid El-Hajbi ◽  
Edouard Chabrun ◽  
Clement Subtil ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Prospective Study ◽  
Disease Relapse ◽  
Faecal Calprotectin ◽  
A Prospective Study

scholarly journals 863 Higher Dietary Fiber Intake is Associated With Lower Risk of Crohn's Disease but Not Ulcerative Colitis - a Prospective Study

2012 ◽  
Vol 142 (5) ◽  
pp. S-148 ◽  
Author(s):  
Ashwin N. Ananthakrishnan ◽  
Hamed Khalili ◽  
Punyanganie S. de Silva ◽  
Joshua R. Korzenik ◽  
Leslie M. Higuchi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Prospective Study ◽  
Dietary Fiber ◽  
Lower Risk ◽  
Fiber Intake ◽  
Dietary Fiber Intake ◽  
A Prospective Study

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

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.

scholarly journals P415 The anti-IL-23/IL-12 agent Ustekinumab is an effective and safe induction therapy in patients with Crohn’s disease refractory or intolerant to anti-TNF: a multicentre Italian study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S379-S379
Author(s):  
A Gubbiotti ◽  
B Barberio ◽  
F Zingone ◽  
R D’Incà ◽  
L Bertani ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Previous Treatment ◽  
Categorical Variables ◽  
Biologic Agent ◽  
Chi Square ◽  
Faecal Calprotectin ◽  
Chi Square Test

Abstract Background There are limited real-life studies in medical literature evaluating the efficacy and safety of Ustekinumab, an Anti-IL-23/Anti IL-12 agent, in patients with Crohn’s disease (CD) who required treatment because of refractoriness or intolerance to previous biological treatments. Thus, the aim of this study was to assess the effectiveness and tolerability of Ustekinumab in anti-TNF refractory or intolerant CD patients. Methods All CD patients who completed induction with Ustekinumab in three Italian IBD Units (Padua, Santorso, and Pisa) were enrolled. Patients were evaluated after induction (first intravenous dose followed by a subcutaneous dose at 8 weeks) and clinical (Harvey- Bradshaw-Index) and biochemical data, including faecal calprotectin (FC) and C-reactive protein (CRP) were collected. Information on the need of optimisation (every 12 or 8 weeks) and adverse events were also collected. Continuous and categorical variables were expressed as mean with standard deviation (sd) and frequency with percentages, respectively. Comparisons between variables were conducted using paired t-test and chi-square test. Data were analysed using STATA11.1 software. Results Sixty-three patients were included (41 males, mean age 43 ± sd 13.2 years). All of them had previously been treated with at least one biologic agent and 95.2% with oral steroids. The main indications for starting therapy were: previous treatment failure (77.2%) and pharmacological intolerance (17.5%). At the time of the induction, 28.6% patients were under steroid treatment. Post induction, clinical remission was obtained in 63.5% patients, while steroid-free clinical remission in 52.4%. Moreover, a statistically significant reduction of FC (from 916 μg/l to 444 μ/l, p < 0.001) and normalisation of CRP (n = 14, 33.3%; p < 0.001) were observed. After induction, 3 adverse effects were reported, and in two treatment discontinuations was necessary (i.e. 1 case of pyelonephritis and 1 case of a re-activation of entero-cutaneous fistula). Finally, among 63 patients enrolled, 51 (80.9%) were optimised with a maintenance regimen of 8 weeks sub-cutaneous doses. Conclusion Our study shows that Ustekinumab seemed is effective in achieving clinical remission and steroid-free clinical remission after induction in the majority of CD patient despite the refractoriness to anti-TNF treatment. Moreover, the drug appeared safe and well tolerated. On the other hand, treatment optimisation to 8 weeks was adopted in most of the patients, in order to guarantee a better outcome.

Sa1864 PROSPECTIVE STUDY OF PHARMACOKINETICS OF INFLIXIMAB DURING INDUCTION IN PATIENTS WITH CROHN'S DISEASE AND ULCERATIVE COLITIS (PACIFIC)

2020 ◽  
Vol 158 (6) ◽  
pp. S-456
Author(s):  
Claire Liefferinckx ◽  
Peter Bossuyt ◽  
Debby Thomas ◽  
Jean-Francois Rahier ◽  
Edouard Louis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Prospective Study

scholarly journals Comparison of Adalimumab Serum Drug Levels When Delivered by Pen Versus Syringe in Patients With Inflammatory Bowel Disease. An International, Multicentre Cohort Analysis

2019 ◽  
Vol 13 (12) ◽  
pp. 1527-1536
Author(s):  
Robert D Little ◽  
Isabel E Chu ◽  
Esmerij P van der Zanden ◽  
Emma Flanagan ◽  
Sally J Bell ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Cohort Analysis ◽  
Drug Level ◽  
Delivery Device ◽  
Faecal Calprotectin ◽  
Drug Levels ◽  
Significant Difference ◽  
The Impact

Abstract Background Adalimumab is administered via a pre-filled syringe or spring-loaded pen. In a previous study in Crohn’s disease, higher drug levels were observed in syringe users. The aim of this study was to evaluate the impact of delivery device on adalimumab drug levels in patients with Crohn’s disease. Methods Consecutive Crohn’s disease patients treated with maintenance adalimumab [40 mg fortnightly] were recruited from five centres. The first recorded drug level with matched clinical and biochemical markers of disease activity was compared between pen and syringe users. Results Of 218 patients, 64% used pen, with a median faecal calprotectin 110 μg/g and serum C-reactive protein 4 mg/L. In comparison to pen, syringe users had higher albumin [39 vs 42 g/L; p = 0.016], lower Harvey-Bradshaw Index [2 vs 1; p = 0.017], and higher rates of concomitant immunomodulation [54% vs 71%; p = 0.014]. Drug levels were equivalent between pen and syringe users [median 5.3 vs 5.2 μg/ml; p = 0.584], even after controlling for disease activity and immunomodulation. Syringe users at Alfred Health had higher drug levels than pen [6.1 vs 4.5 μg/ml; p = 0.039]; a greater proportion achieved therapeutic levels [75% vs 44%; p = 0.045]. A higher proportion of pen users from Saint-Étienne had therapeutic levels [79% vs 42%; p = 0.027], yet no significant difference in drug levels [7.9 vs 4.5 μg/ml; p = 0.119]. Conclusions Delivery device does not appear to significantly affect adalimumab drug levels. Given differences between study sites, studies evaluating administration education and technique are warranted.

Mo1690 A Prospective Single Centre Evaluation of the Intra-Individual Variability of Faecal Calprotectin in Quiescent Crohn's Disease Patients

2012 ◽  
Vol 142 (5) ◽  
pp. S-660
Author(s):  
Lyn A. Smith ◽  
Graham Naismith ◽  
Joanna I. Munro ◽  
Karen Rankin ◽  
Sarah Barry ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Individual Variability ◽  
Single Centre ◽  
Faecal Calprotectin

scholarly journals P603 Persistence of vedolizumab maintenance therapy: Findings from a Belgian registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S503-S504
Author(s):  
E Louis ◽  
V Muls ◽  
P Bossuyt ◽  
A Colard ◽  
A Nakad ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Disease Activity ◽  
Real World ◽  
Clinical Remission ◽  
Disease Activity Score ◽  
Activity Score

Abstract Background Clinical trials and observational studies have demonstrated the clinical efficacy of vedolizumab (VDZ) as maintenance therapy for Crohn’s disease (CD) and ulcerative colitis (UC). This report presents long-term data on persistence of VDZ maintenance therapy in real-world clinical practice in Belgium. Methods The Belgian VDZ Registry (ENCePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres across Belgium. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months after enrolment with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as the Harvey–Bradshaw Index (HBI) <5 or partial Mayo Score (pMS) <2. Missing value imputation (last observation carried forward) was used to partially account for missing disease activity scores. If a 6-monthly disease activity score was missing, the disease activity score from the previous 6-monthly assessment was used. Results The mean duration of VDZ therapy, including use prior to enrolment, was 31 months, with 68% of CD patients and 75% of UC patients using VDZ therapy for 48 months. Clinical remission rate after 42 months of VDZ therapy was higher in UC (84%) than CD (67%), and higher for patients without prior anti-TNF therapy (87%) than those with prior anti-TNF therapy (70%). Fifty-seven (29.4%) patients discontinued VDZ during follow-up, due to loss of response (n = 40), adverse event (n = 7), clinical remission (n = 4), pregnancy planning (n = 3), and patient choice (n = 3). Conclusion These real-world long-term Belgian data demonstrate a high persistence of VDZ maintenance therapy among both CD and UC patients, with highest clinical remission rates seen in patients with UC and those with no prior anti-TNF therapy.

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

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