scholarly journals DOP51 De-escalation of biological therapy in Inflammatory Bowel Disease patients following prior escalation

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S086-S086
Author(s):  
P Thomas ◽  
L Smits ◽  
M Te Groen ◽  
R West ◽  
M Russel ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Bowel Disease ◽  
Biological Therapy ◽  
Limited Data ◽  
Faecal Calprotectin ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
Biological Dose ◽  
Trough Levels

Abstract Background There are limited data available on de-escalation of biological therapy after prior escalation in inflammatory bowel disease (IBD) patients. The aim of this study was to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and evaluate which measures are used prior to de-escalation. Methods This multicentre, prospective, cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated at least once after prior biological escalation. Objective disease measures for de-escalation were defined as faecal calprotectin ≤ 200 µg/g and/or therapeutic or supratherapeutic trough levels and/or radiologic or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for ≥6 months after de-escalation. Results In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these, 34 (17%) patients on IFX, 18 (21%) patients on ADA and 8 (15%) patients on VEDO had received at least one subsequent de-escalation. De-escalation was successful in 91% of IFX patients, 89% of ADA patients and 100% of VEDO patients. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. De-escalation based on objective disease measures was performed in 67% of all de-escalations. Objective de-escalations were successful in 98% versus 80% of subjective de-escalations. Conclusion De-escalation after biological escalation is successful in the majority of patients. Objective markers of remission increase the likelihood of successful de-escalation.

scholarly journals P389 Post induction infliximab trough levels predict long-term endoscopic remission in paediatric patients with inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S362-S363
Author(s):  
K van Hoeve ◽  
E Dreesen ◽  
I Hoffman ◽  
M Ferrante ◽  
S Vermeire
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Drug Exposure ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Although higher infliximab (IFX) trough levels (TL) have been associated with better outcomes, the ideal predictive sampling time and cut-points to achieve endoscopic remission remain unclear in children with inflammatory bowel disease (IBD). Therefore, we evaluated the pharmacokinetics of IFX during induction to predict long-term outcome of IFX. Methods All children with Crohn’s disease (CD) or ulcerative colitis (UC) starting IFX therapy (5 mg/kg at weeks 0–2–6–12) for active luminal disease from May 2017 till May 2019 were followed prospectively. IFX levels were measured by Ridascreen IFX Monitoring ELISA (TL at weeks 2–6–12, peak at weeks 0–2–6 and intermediate at weeks 1–4). IFX levels and cumulative drug exposure (area under the curve (AUC) till week 12) were correlated with the outcome at month 6. Clinical remission was defined as PUCAI/PCDAI <10, biochemical remission as CRP ≤5 mg/l + ESR ≤20 mm/h, endoscopic remission as SES-CD <3 or Mayo endoscopic sub-score = 0 and deep remission if both clinical + endoscopic remission. Results were analysed using Mann–Whitney U-test (presented as median [IQR]). Results A total of 252 serum induction levels were included from 32 patients (20 CD and 12 UC; 38% male; median age at start of IFX 13.8 years [11.3–14.9]; 84% on concomitant thiopurines). Clinical remission was achieved in 24 (75%) patients and 18 (56%) were in endoscopic remission (all in deep remission) at month 6. Endoscopic remission at month 6 was associated with significantly higher median IFX TL at week 4 (38.8 µg/ml [24.3–46.0] vs. 23.5 µg/ml [10.5–36.6], p = 0.017), at week 6 (19.9 µg/ml [10.1–26.3] vs. 11.1 µg/ml [3.7–19.9], p = 0.031), at week 12 (9.6 µg/ml [5.5–11.9] vs. 3.5 µg/ml [2.7–7.2], p = 0.004; fig1.) and higher AUC week 0–12 (4574.7 µg*day/ml [3783.0–5160.8] vs. 3722.9 µg*day/ml [3102.2–3991.9], p = 0.008). Median IFX TL at week 12 were significantly higher in children with clinical remission (8.6 µg/ml [5.1–12.0] vs. 4.3 µg/ml [3.1–5.9], p = 0.033), but not for biological remission (6.7 µg/ml [4.0–12.0] vs. 4.3 µg/ml [1.2–7.2], p = 0.250; Figure 2) at month 6. ROC analysis identified an IFX TL at week 12 ≥ 5.0 µg/ml and an AUC weeks 0–12 ≥ 4056.0 µg*day/ml as minimal target to achieve endoscopic remission at mo. 6 (AUROC: 0.796 [95% CI: 0.62–0.97] and AUROC: 0.778 [95% CI: 0.61–0.94], respectively; Figure 3.). Height, haemoglobin and PCDAI score at start of IFX therapy, significantly correlated with week 12 IFX TL. Conclusion Adequate IFX exposure during induction in paediatric IBD patients is associated with significantly better clinical, endoscopic and deep remission rates at month 6. Model-informed precision dosing can assist physicians to achieve optimal exposure during induction more precisely (and rapidly) what is essential for an optimal outcome.

scholarly journals P318 Association between faecal calprotectin values and infliximab trough levels in inflammatory bowel disease patients

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S261-S262
Author(s):  
L Rodriguez Alonso ◽  
K Serra ◽  
E Santacana ◽  
N Padullés ◽  
C Arajol ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Faecal Calprotectin ◽  
Inflammatory Bowel ◽  
Trough Levels

scholarly journals A157 THE EFFECTIVENESS OF A STANDARDIZED BIOLOGIC CARE PATHWAY IN THE MANAGEMENT AND TREATMENT OF INFLAMMATORY BOWEL DISEASE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 21-22
Author(s):  
N Willett ◽  
C Heisler ◽  
N Nazer ◽  
B Currie ◽  
K Phalen-Kelly ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Combination Therapy ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Multivariate Analyses ◽  
Care Pathway ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
The Mean

Abstract Background Inflammatory Bowel Disease (IBD) is a class of chronic immune-mediated diseases. Biologics have revolutionized the treatment of IBD. Existing literature suggests significant variation exists in the use of biologic treatment among physicians, from provider-specific prescribing to completion of the pre-biologic workup. These differences may influence the effectiveness of achieving and maintaining long-term remission. Clinical care pathways may serve to standardize the use of biologics in the treatment of IBD leading to improvements in patient outcomes and consistency of care provided from different specialists. Aims To determine if the use of biologics to treat IBD managed within a standardized biologic care pathway (BCP) is safer and more effective compared to the current standard of care. Methods This was a retrospective, real-world cohort study of a prospectively implemented evidence-based BCP at the Nova Scotia Collaborative IBD (NSCIBD) program between 2015 and 2019. Patient inclusion criteria consisted of any adult with a diagnosis of IBD (including Crohn’s Disease, ulcerative colitis, IBD-Unclassified) aged 18 years or older who was managed within the NSCIBD program. Preliminary descriptive analyses of the data are presented. Data collection is ongoing and multivariate analyses will be presented in full at CDDW. Results In total 249 patients were included in the cohort study (111 BCP patients, 138 non-BCP patients). The mean age was 49 years (range of 17–86 years). Sixty-nine percent (171/249) of patients were diagnosed with CD, 28% (70/249) with UC, and 3% (8/249) with IBD-U. The mean duration of disease was 13 years (range of 0–36 years). Use of combination therapy was similar between the cohorts with 64% of BCP patients (n=102) and 63% of non-BCP patients (n=123) on combination therapy. Thirty-eight percent of the BCP cohort required dosing interval changes vs. 29% in the non-BCP cohort (0.24 fold higher in BCP cohort). Seventy-one percent of the BCP patients were exposed to TDM vs. 41% of the non-BCP cohort (0.40-fold more TDM in pathway cohort). Although 34% of BCP patients and 38% of non-BCP cohort patients reached clinical remission (n=103 and 125, respectively), 38% of BCP patients and 21% of non-BCP patients achieved endoscopic remission (0.5-fold lower in the non-BCP cohort), (n=29 and 53, respectively). Conclusions Preliminary analyses suggest patients managed within a BCP have their biologic management guided more often by the results of TDM and objective biomarkers than those not managed within a BCP. Although clinical remission was observed to be similar between the cohorts, attainment of endoscopic remission was more likely amongst patients managed within the BCP. Additional multivariate analyses will be presented at CDDW with a larger cohort size. Funding Agencies None

scholarly journals OP20 The gut microbiota during biological therapy for inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S016-S018
Author(s):  
C Caenepeel ◽  
S Viera-Silva ◽  
B Verstockt ◽  
K Machiels ◽  
N A Davani ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Biological Therapy ◽  
Longitudinal Impact ◽  
Faecal Microbiota ◽  
Faecal Calprotectin ◽  
Cell Counts ◽  
Inflammatory Bowel ◽  
Associated Variables

Abstract Background The expansion of therapeutic options in IBD brought forward a need to personalise treatment. Gut inflammation in inflammatory bowel disease (IBD) patients has been associated with reduced microbial richness and abundance of SCFA producers. We aimed to explore the longitudinal impact of treatment on the inflammatory burden and faecal microbiota in patients with CD and UC, treated with anti-tumour necrosis factor (anti-TNF) therapy, vedolizumab (VDZ) or ustekinumab (UST). Methods We analysed faecal samples from 349 IBD patients (112 UC, 237 CD) initiating biological therapy (anti-TNF; VDZ; UST), regardless baseline disease activity, between 2010 and 2019 at a tertiary referral centre. Samples were collected at week 0, 14 and 24. Microbiota phylogenetic profiling was conducted by 16S rRNA gene sequencing and faecal cell counts were determined using flow cytometry. Moisture levels were measured using lyophilisation. Disease activity and response were assessed by faecal calprotectin (FCal). Statistics were performed in R, v3.5.1. Enterotyping was based on the Dirichlet multinomial mixtures approach. Results Faecal microbiota profiles showed high diversity, with samples classified into all four enterotypes (Fig1), although Bact2 was 6- to 10-fold more prevalent in patients compared with controls (Fig2). The variation in faecal microbiota composition was explained (multivariate dbRDA) by diagnosis (R2 = 1.2%, p = 1.00E−04), timepoint (R2 = 0.52, p = 0.006), significantly by age, gender and faecal moisture. The full model only explained 2.85% of the microbiota variation. A slight non-significant decrease in the Bact2 enterotype prevalence was observed in the CD, but not in the UC cohort, during treatment. A significant decrease in FCal concentrations (w0 vs. 14, UC p = 5.12E-08, CD p = 2.56E−08; week 0 vs. 24: CD p = 4.86E-08) was observed with treatment, accompanied by a significant increase in cellcounts (w0 vs. 14: UC p = 0.024, CD p = 0.0022; week 0 vs. 24: CD p = 0.0201) (Figure 3). No significant change in Bact2 prevalence was found during treatment. Only treatment-associated variables—week of treatment (p = 2.4E−18), diagnosis (0.0005) and timepoint (p = 0.0073)—were significant predictors for response, while microbiota-associated variables (enterotype, cell counts and faecal moisture) not. Baseline samples were associated with higher FCal levels. This suggests that the response time of the microbiota to treatment may be higher than the host inflammatory response. Conclusion The prevalence of the inflammatory Bact2 enterotype was 5- to 10-fold higher in CD and UC patients as compared with controls. Although initiation of biological therapies leads to a decrease in inflammation levels as witnessed by faecal calprotectin and increase in microbial richness, a shift in enterotypes did not occur.

scholarly journals P480 Assessing primary response to biologic therapy in Inflammatory Bowel Disease - ‘the when and the how?’

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S470-S470
Author(s):  
A C Moore ◽  
S Peake
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Biological Therapy ◽  
Biologic Therapy ◽  
Clinical Symptoms ◽  
Primary Response ◽  
Mucosal Inflammation ◽  
Faecal Calprotectin ◽  
Blood Tests ◽  
Inflammatory Bowel

Abstract Background ECCO guidelines state that patients started on biologic therapy for Inflammatory Bowel Disease (IBD) should be reviewed between week 10 and 16 depending on the biologic used and response assessed using predefined objective criteria. The study aim was to ascertain, the time point, and by which methods patients with IBD are being assessed for primary response. Methods A retrospective chart review was conducted of 50 consecutive patients with IBD who had been started on biological therapy between October 2018 and June 2019 at a tertiary referral university teaching hospital in London, UK. Results Patients were started on 5 biologics; infliximab (20 patients), adalimumab (11 patients), vedolizumab (6 patients), ustekinumab (9 patients) and tofacitinib (4 patients). Twenty two patients had Ulcerative Colitis and 28 patients had Crohn’s Disease. All 50 patients were still receiving biological therapy at the time of their first assessment in a consultant led IBD clinic. On average, patients were assessed at week 13 for primary response. Figure 1 outlines the time to assessment of disease response, according to the biologic used. The most frequently used methods were clinical symptoms (49 patients, 98%) and blood tests (47 patients, 94%). Disease activity scores were rarely documented. Other methods of disease assessment were faecal calprotectin (13 patients, 26%), ileocolonoscopy (11 patients, 22%) and radiological studies (2 patients, 4%). Only 19 patients (38%) had either a faecal calprotectin or a colonoscopy ordered at their appointment. Thirteen patients (26%) had undergone an endoscopic assessment of their disease when the data was analysed in December 2019. Conclusion Patients are being assessed in a timely fashion for primary response to biological therapy, in line with current ECCO guidelines. Clinical symptoms and blood tests are being heavily relied on to assess for primary response to therapy. Patient-reported symptoms do not correlate well with mucosal inflammation in IBD1. Faecal Calprotectin, as a surrogate marker of mucosal inflammation, and colonoscopy are being underused. Potential reasons for the low rates of colonoscopy may include patient’s wishes and lack of endoscopy capacity. The importance of a mucosal healing assessment is imperative to be able to optimise treatment appropriately and improve long-term outcomes for our patients. Reference

scholarly journals P338 The effectiveness of a standardised biologic care pathway in the management and treatment of inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S325-S325
Author(s):  
N Willett ◽  
C G Heisler ◽  
N Nazer ◽  
B Currie ◽  
K Phalen-Kelly ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Combination Therapy ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Multivariate Analyses ◽  
Care Pathway ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
The Mean

Abstract Background inflammatory bowel disease (IBD) is a class of chronic immune-mediated diseases. Biologics have revolutionised the treatment of IBD. Existing literature suggests significant variation exists in the use of biologic treatment among physicians, from provider-specific prescribing to completion of the pre-biologic workup. These differences may influence the effectiveness of achieving and maintaining long-term remission. Clinical care pathways can standardise the use of biologics, improve patient outcomes, and increase consistency of care. The aim of the project was to determine whether the use of biologics to treat IBD managed within a standardised biologic care pathway (BCP) is safer and more effective compared with the current standard of care. Methods This was a retrospective, real-world cohort study of a prospectively implemented evidence-based BCP at the Nova Scotia Collaborative IBD (NSCIBD) program between 2015 and 2019. Patient inclusion criteria consisted of an adult with a diagnosis of IBD (including Crohn’s disease, ulcerative colitis, IBD-Unclassified) aged 18 years or older who was managed within the NSCIBD program. Preliminary descriptive analyses of the data are presented. Data collection is ongoing and multivariate analyses will be presented in full at ECCO. Results In total 249 patients were included in the cohort study (111 BCP patients, 138 non-BCP patients). The mean age was 49 years (range of 17–86 years). Sixty-nine per cent (171/249) of patients were diagnosed with CD, 28% (70/249) with UC, and 3% (8/249) with IBD-U. The mean duration of disease was 13 years (range of 0–36 years). Use of combination therapy was similar between the cohorts with 64% of BCP patients (n = 102) and 63% of non-BCP patients (n = 123) on combination therapy. Thirty-eight per cent of the BCP cohort required dosing interval changes vs. 29% in the non-BCP cohort (0.24 fold higher in BCP cohort). Seventy-one per cent of the BCP patients were exposed to TDM vs. 41% of the non-BCP cohort (0.40-fold more TDM in pathway cohort). Although 34% of BCP patients and 38% of non-BCP cohort patients reached clinical remission (n = 103 and 125, respectively), 38% of BCP patients and 21% of non-BCP patients achieved endoscopic remission (0.5-fold lower in the non-BCP cohort), (n = 29 and 53, respectively). Conclusion Preliminary analyses suggest patients managed within a BCP have their biologic management guided more often by the results of TDM and objective biomarkers than those not managed within a BCP. Although clinical remission was observed to be similar between the cohorts, attainment of endoscopic remission was more likely amongst patients managed within the BCP. Additional multivariate analyses will be presented at ECCO with a larger cohort size.

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