Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn’s Disease Might Be Associated With Increased Rates of Stoma Construction.

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn’s disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results: Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions: Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors.post-print179 K

Circulating cytokines and cytokine receptors in infliximab treatment failure due to TNF-α independent Crohn disease

The inflammatory response at infliximab (IFX) treatment failure due to tumor necrosis factor (TNF)-α-independent Crohn disease activity is unknown. This is an exploratory, hypothesis-generating study based on samples collected in a clinical trial among patients failing conventional IFX dosages and treated with an intensified IFX regimen for 12 weeks. Patients with clinical response at week 12, as defined by a reduction of Crohn disease activity index by ≥70, were considered to suffer from nonimmune pharmacokinetic (PK) treatment failure (n = 18), and nonresponders had a presumed pharmacodynamic (PD) failure due to non-TNF-driven disease (n = 8). Patients failing IFX due to functional anti-IFX antibodies (n = 2) were excluded. The study population also comprised a group of 12 patients in long-term remission on IFX. A functional cell-based reporter gene assay was applied to measure IFX and anti-IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic protein 1. The IFX levels were similar between patients with IFX failure caused by nonimmune PK or PD at treatment failure (median 1.4 vs 2.4 μg/mL; P = 0.52), during treatment intensification (8.1 vs 5.6; P = 0.85), and after 12 weeks (8.8 vs 7.7; P = 0.93), congruent with nonresponders failing IFX due to predominantly TNF-α-independent signaling pathways in their disease. Cytokine and cytokine receptor levels were comparable between patients with nonimmune PK failure and PD failure at time of manifestation of IFX failure, but with higher IL-6 and sTNF-R2 levels among IFX treatment failures as compared with patients in remission (IL-6 median 3.6 vs <3.1 pg/mL; P = 0.03; sTNF-R2 3207 vs 2547 pg/mL; P = 0.01). IL-6 and sTNF-R2 were lower after 12 weeks in nonimmune PK failures than in PD failures (<3.1 vs 4.0; P = 0.02; 3209 vs 4740; P = 0.04, respectively), and were measured at levels comparable with patients in remission. Further, trends of decreased IL-6 and sTNF-R2 levels among nonimmune PK failures during IFX intensification (P < 0.05 and P = 0.12) were observed. These observations indicate that IL-6 and sTNF-R2 are of potential relevance in driving the inflammatory response in IFX refractory Crohn disease caused by TNF-α-independent disease activity

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn’s Disease Might Be Associated With Increased Rates of Stoma Construction

Crohn’s disease; Abscess; StomaMalaltia de Crohn; Abscés; EstomaEnfermedad de Crohn; Absceso; EstomaBackground Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn’s disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease

Background: One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors.Methods: Successive serum samples collected during IFX induction treatment (weeks 0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1H nuclear magnetic resonance (NMR) spectroscopy. Data were analysed with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB.Results: Metabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn's disease and controls, and quiescent Crohn's disease and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially distinct group based on their metabolic profile, although no applicable response biomarkers could be singled out in the current setting.Conclusion: 1H NMR spectroscopy of serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With its use, we provide unique insights into the metabolic changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD

Therapeutic drug monitoring in inflammatory bowel disease : implementation, utilization, and barriers in clinical practice in Scandinavia

Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p 10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.Peer reviewe

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results: Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P &lt; .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions: Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors

Efficacy and safety of methotrexate in the management of inflammatory bowel disease: a systematic review and meta-analysis of randomized, controlled trials

Background: The therapeutic role of methotrexate (MTX) for management of inflammatory bowel disease (IBD) remains unclear. Methods: We systematically reviewed randomized, controlled trials (RCTs) of MTX for induction and maintenance of remission in IBD until January 2020 in accordance with PROSPERO protocol (#CRD42018115047). Relative risk (RR) of maintenance of remission, induction of remission, endoscopic disease activity, and adverse events were combined in a meta-analysis. Findings: MTX monotherapy was not superior to placebo for induction of clinical remission in Crohn's disease (CD). However, MTX was superior to placebo in maintaining clinical remission of CD. Concomitant therapy with MTX and the TNF inhibitor infliximab (IFX) was not superior to IFX monotherapy in CD. In ulcerative colitis (UC), MTX monotherapy was not superior to placebo neither for induction of clinical remission, nor for maintenance of clinical remission. MTX did not result in superior endoscopic outcomes during induction or maintenance therapy compared with placebo. Regarding adverse events (AEs), our meta-analysis on CD studies showed a significantly higher risk of AEs when comparing MTX versus placebo in studies investigating induction of remission, but not in maintenance of remission. In UC, no such differences in AEs between MTX or placebo were observed. Interpretation: Current data support the efficacy of parenteral MTX monotherapy for maintenance of clinical remission in CD. MTX is not confirmed to be effective for treatment of UC or for induction of remission in CD. No evidence supports concomitant MTX to improve efficacy of IFX (no other biologics investigated)