Tu1862 BI 695501 DEMONSTRATES SIMILAR EFFICACY AND COMPARABLE SAFETY TO ADALIMUMAB REFERENCE PRODUCT IN PATIENTS WITH ACTIVE CROHN'S DISEASE: FINAL ANALYSIS OF THE PHASE III VOLTAIRE-CD STUDY

2020 ◽  
Vol 158 (6) ◽  
pp. S-1192-S-1193
Author(s):  
Stephen B. Hanauer ◽  
Stefan Schreiber ◽  
Sigrid E. Balser ◽  
Ekkehard Brockstedt ◽  
Viktoria Moschetti ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Reference Product ◽  
Final Analysis ◽  
Similar Efficacy ◽  
Phase Iii

Improvement of a ‘Leaky' Intestinal Barrier

2017 ◽  
Vol 35 (1-2) ◽  
pp. 21-24 ◽  
Author(s):  
Eduard F. Stange
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Barrier ◽  
Bacterial Attachment ◽  
Phase Iii ◽  
Colonic Disease ◽  
Mucus Layer ◽  
Tissue Destruction ◽  
Liquid Form ◽  
Mucus Production

In Crohn's disease, the mucus layer appears to be defective in terms of low defensin levels and lack of antibacterial activity. These deficiencies actually explain the Montreal phenotypes and the stable localization of disease in the terminal ileum with low α-defensins from Paneth cells and/or low β-defensins in colonic disease, respectively. Conversely, in ulcerative colitis (UC) the defensin production is normal or even induced, but the mucus layer is thinner and patchy, more in the liquid form and also chemically altered so that antibacterial peptides are not retained and lost into the luminal bacterial bulk. Therefore, both barrier problems allow slow bacterial attachment and invasion, ultimately triggering the massive response of adaptive immunity and tissue destruction. Therefore, leakiness should refer to the antibacterial barrier and not to the general barrier against small molecules, such as mannitol or lactulose, which are not antigenic. The most promising approach in UC seems to be the use of probiotics or the natural compound lecithin as a stabilizer of mucus structure to enhance the barrier. While a phase II study has yielded positive results, the results of the ongoing phase III study are eagerly awaited. It is quite possible that the protective effect of smoking in UC is related to mucus production in the colon also, but this is not an option. Another alternative would be to shift cell differentiation in the colon towards goblet cell; the relevant differentiation factors are known. In Crohn's disease, the direct oral application of defensins might be effective if release and binding to the mucus are achieved. In the experimental colitis model, this works quite well. In conclusion, in a situation where enthusiasm about so-called biologics is declining due to loss of response over time, searching for the primary defects in inflammatory bowel disease and treating them may well be worthwhile, although it is unlikely to provide rapid relief.

scholarly journals Levels of TB-IGRA may help to differentiate between intestinal tuberculosis and Crohn’s disease in patients with positive results

2020 ◽  
Vol 13 ◽  
pp. 175628482092200
Author(s):  
Yujie Zhao ◽  
Meilin Xu ◽  
Liang Chen ◽  
Zhanju Liu ◽  
Xiaomin Sun
Keyword(s):  
Weight Loss ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Tuberculosis ◽  
Clinical Manifestations ◽  
Final Analysis ◽  
Interferon Gamma Release Assay ◽  
Significant Difference ◽  
History Of ◽  
Diagnosis Criteria

Aim: The aim of this study was to investigate the significance of positive tuberculosis interferon gamma release assay (TB-IGRA) in the differential diagnosis of intestinal tuberculosis (ITB) and Crohn’s disease (CD) patients, and to find a suitable threshold to help distinguishing CD from tuberculosis (TB), so as to provide better recommendations for clinical treatment. Methods: A retrospective study was performed including 484 patients who underwent TB-IGRA testing for suspected CD or ITB treated in the Shanghai Tenth People’s Hospital of Tongji University between January 2015 and May 2018. According to the diagnostic criteria, 307 patients, including 272 CD and 35 ITB patients, were recruited for the final analysis. We comprehensively and systematically collected their clinical manifestations, and analyzed the influence of TB-IGRA values referring to diagnosis criteria, and the possible causes of false positives. The receiver operator characteristic (ROC) curve and the cut-off value were applied to distinguish between ITB and CD patients. Results: Of the 56 patients with suspected CD enrolled, 23 were finally diagnosed with CD and 33 with ITB. In patients with TB-IGRA ⩾ 100 pg/ml, 4 cases were CD and 29 cases were ITB, while 19 cases were CD and 4 cases were ITB in patients with TB-IGRA < 100 pg/ml ( p < 0.05). TB-IGRA ⩾ 100 pg/ml indicated a high possibility of TB infection, with a sensitivity of 88% and a specificity of 74%. Three out of the four CD patients with TB-IGRA ⩾ 100 pg/ml had a history of tuberculosis, while only 1 of the 19 CD patients with TB-IGRA < 100 pg/ml had a history of tuberculosis ( p < 0.05). The average duration of ITB was 7 months, and that of CD was 46.8 months, thus a significant difference ( p < 0.05) was observed. Perianal lesions such as anal fistula or abscess were found in all CD patients. Among ITB patients, 8 out of 15 patients with TB-IGRA ⩾ 400 pg/ml experienced weight loss, while only 1 out of 18 patients with TB-IGRA < 400 pg/ml underwent weight loss ( p < 0.05). Conclusion: Patients with CD have longer duration of disease, and perianal lesions are more common in CD. ITB patients with TB-IGRA ⩾ 400 pg/ml experience weight loss more readily, which indicates that TB-IGRA value may be correlated positively with the severity of ITB. In patients with CD and ITB, TB-IGRA = 100 pg/ml may be a cut-off value of TB-IGRA. For patients with TB-IGRA ⩾ 100 pg/ml, it is recommended to use diagnostic anti-TB treatment first. Comprehensive analysis and judgment are required for patients with TB-IGRA from 14 pg/ml to 99 pg/ml. TB-IGRA false positivity may occur in patients with a history of TB infection.

scholarly journals Efficacy of JAK inhibitors in Crohn’s Disease

2019 ◽  
Vol 14 (Supplement_2) ◽  
pp. S746-S754 ◽  
Author(s):  
Gerhard Rogler
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Development ◽  
Phase Iii ◽  
Jak Inhibitor ◽  
Jak Inhibitors ◽  
Janus Kinases ◽  
Double Blinded

Abstract Inhibition of Janus kinases [JAKs] in Crohn’s disease [CD] patients has shown conflicting results in clinical trials. Tofacitinib, a pan-JAK inhibitor, showed efficacy in ulcerative colitis [UC] and has been approved for the treatment of patients with moderate to severe UC. In contrast, studies in CD patients were disappointing and the primary end point of clinical remission could not be met in the respective phase II induction and maintenance trials. Subsequently, the clinical development of tofacitinib was discontinued in CD. In contrast, efficacy of filgotinib, a selective JAK1 inhibitor, in CD patients was demonstrated in the randomized, double-blinded, placebo-controlled phase II FITZROY study. Upadacitinib also showed promising results in a phase II trial in moderate to severe CD. Subsequently, phase III programmes in CD have been initiated for both substances, which are still ongoing. Several newer molecules of this class of orally administrated immunosuppressants are being tested in clinical programmes. The concern of side effects of systemic JAK inhibition is addressed by either exclusively intestinal action or higher selectivity [Tyk2 inhibitors]. In general, JAK inhibitors constitute a new promising class of drugs for the treatment of CD.

scholarly journals P606 Exclusive enteral nutrition with a polymeric diet is efficacious in inducing remission in adults with active Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S505-S508
Author(s):  
P Kakkadasam Ramaswamy ◽  
R Mutsekwa ◽  
X Lan ◽  
Y Chen ◽  
R Angus ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Induction Therapy ◽  
Final Analysis ◽  
Adult Patients ◽  
Current Smoking ◽  
Exclusive Enteral Nutrition ◽  
Male Sex ◽  
Disease Location

Abstract Background Exclusive Enteral nutrition (EEN) is not routinely used as induction therapy for adults with active Crohn’s disease (CD)due to limited adherence and palatability. The aim of this study was to assess the efficacy, tolerability and safety of EEN in adult patients with CD. Methods Retrospective analysis of data from patients with active CD who underwent induction therapy with EEN at a single centre from January 2018 to July 2019. All patients who completed at least 4 weeks of polymeric EEN diet were included in the final analysis. Primary Endpoint (PE) was steroid-free clinical remission (CDAI ≤150) or response (100 point decrease in CDAI) at the end of therapy. Secondary endpoint (SE) was achievement of biochemical remission (CRP &lt;5 mg/l or Calprotectin &lt;150 μg/g) at 8–10 weeks. Results Sixty-three patients were initiated on EEN, 50 patients who completed at least 4 weeks of EEN were included in the final analysis. Mean age was 42.4 years, 25 (50%) were females. Mean CDAI score at baseline was 260. Forty per cent of patients were on concurrent biologics and 66.6% were on concurrent immunomodulators. At the completion of EEN, 72% (36/50) of patients achieved PE (29 remission, 7 response). SE was achieved in 65.7% (23/35) of patients. EEN duration ≥ 6 weeks was more likely to achieve PE (75% vs. 55.5%, OR 2.7, P 0.01) and SE (71% vs. 25%, OR 7.3, P 0.001).EEN duration &lt; 6 weeks and current smoking were less likely to achieve PE and SE. Patients with concomitant steroid use at baseline had PE of 77.7% (vs. 68.8% with EEN alone; OR 0.9, P 0.5), and SE of 66.6% (vs. 60.9% with EEN alone, OR 0.77, P 0.74). Disease location, behaviour, sex, disease duration, concurrent biologic use or concurrent immunomodulator use did not affect the PE or SE. Six patients reported adverse effects (3 nausea,2 diarrhoea,1 constipation). Male sex, ileal location, B2/B3 phenotype were more likely to complete a 6 week EEN course. Conclusion Polymeric EEN is well-tolerated, safe and efficacious in inducing remission in adults with active CD. EEN duration of ≥ 6 weeks has better outcomes. EEN alone or in combination with steroids induces remission in adult patients with active CD. Further controlled trials using polymeric EEN are necessary.

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