Tu1846 PHASE 2A PROOF OF CONCEPT PLACEBO CONTROLLED STUDY WITH ORAL ABX464 50MG QD IN ULCERATIVE COLITIS SHOWS ENDOSCOPIC IMPROVEMENT WITH LOSS OF MICROSCOPIC DISEASE ACTIVITY IN MOST ENDOSCOPIC RESPONDERS

2020 ◽  
Vol 158 (6) ◽  
pp. S-1185
Author(s):  
Gert De Hertogh ◽  
Jean-Marc Steens ◽  
Julien Santo ◽  
Paul Gineste ◽  
Severine Vermeire
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Controlled Study ◽  
Proof Of Concept

scholarly journals A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis

2021 ◽  
Vol 8 (1) ◽  
pp. e000680
Author(s):  
Kathy Weisel ◽  
Nicola Scott ◽  
Scott Berger ◽  
Susanne Wang ◽  
Kurt Brown ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ulcerative Colitis ◽  
Disease Activity ◽  
Controlled Study ◽  
Experimental Medicine ◽  
Open Label ◽  
Double Blind ◽  
Treatment Groups ◽  
To Receive

ObjectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.DesignIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.ResultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.ConclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC.Trial registration numberNCT02903966.

scholarly journals P146 Comparison of three histologic indices in ulcerative colitis: Evaluation from the Phase 2 study of upadacitinib (U-ACHIEVE)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S210-S211
Author(s):  
V Jairath ◽  
W J Lee ◽  
W Zhou ◽  
G Heap ◽  
J Butler ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Financial Support ◽  
Missing Values ◽  
Mucosal Inflammation ◽  
Controlled Study ◽  
Physician Global Assessment ◽  
Double Blind ◽  
Faecal Calprotectin ◽  
Reactive Protein

Abstract Background Several histologic indices are available for evaluating mucosal inflammation activity in ulcerative colitis (UC), although there is no consensus regarding which is the most appropriate for evaluating disease activity in clinical trials. Methods The correlation of three histologic indices, the Geboes Score (GS, range of major grade 0 to 5), Robarts Histopathology Index (RHI, range 0 to 33), and Nancy Index (NI, range grade 0 to grade 4) were evaluated in a Phase 2b, multicenter, randomised, double-blind, placebo-controlled study of upadacitinib in patients with moderately to severely active UC. Biopsy data were collected and centrally read using GS at Baseline and week 8; scores of RHI1 and NI2 were derived based on GS. Descriptive statistics, correlational analyses, and stratified analyses were performed in the pooled study population using as observed data. Results Among 250 UC patients enrolled at Baseline, 224, 214, 209 patients with non-missing values of GS, RHI and NI were observed, respectively. At week 8, the GS, RHI, and NI correlated strongly to each other (r = 0.90 to 0.98), and these 3 indices correlated highly with the subgrade of lamina propria neutrophils, erosion or ulceration, neutrophils in the epithelium, and chronic inflammatory infiltrate (Table 1). The Mayo endoscopic subscore (r = 0.62) was found to have higher correlation with GS, RHI and NI, followed by physician global assessment subscore (r = 0.48 to 0.51), rectal bleeding subscore (r = 0.36 to 0.39) and stool frequency subscore (r = 0.31 to 0.33). Faecal calprotectin (r = 0.47 to 0.50) and C-reactive protein (0.36 to 0.39) and total IBDQ score (r = 0.34 to 0.38) were moderately correlated with GS, RHI, and NI. Over 50% of patients with Mayo endoscopic subscore ≤1 were observed among patients scoring GS = 0 (24/41, 59%), GS = 1 (8/15, 53%), GS = 2 (13/26, 50%), RHI≤3 (45/82, 55%), and NI = 0 (40/69, 58%) at week 8. Conclusion In a moderately to severely active UC population, GS, RHI and NI correlate strongly with each other. Higher correlations were found between histologic scores and endoscopic activity than symptom-related disease activity. Further studies are warranted to evaluate the relationship between histological inflammation and long-term clinical outcomes. References Acknowledgements and Funding statement: Design, study conduct, and financial support for the study were provided by AbbVie; Financial support for the study was provided by AbbVie. AbbVie participated in interpretation of data, review, and approval of the abstract. All authors contributed to development of the abstract and maintained control over final content.

scholarly journals A Double-Blind, Placebo Controlled, Multicentre Study of the Efficacy And Safety of 5-Aminosalicylic Acid Tablets in the Treatment of Ulcerative Colitis

1990 ◽  
Vol 4 (7) ◽  
pp. 463-467 ◽  
Author(s):  
LR Sutherland ◽  
M Robinson ◽  
G Onstad ◽  
M Peppercorn ◽  
N Greenberger ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Global Assessment ◽  
Activity Index ◽  
Disease Activity Index ◽  
Controlled Study ◽  
Active Ulcerative Colitis ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Double Blind Placebo

This double-blind, placebo controlled, multicentre, parallel trial assessed the efficacy of two oral doses of a new formulation of 5-aminosalicylic acid (5-ASA) targeted to release in the cecum which was given for six weeks to 136 patients with active ulcerative colitis. Seven centres participated (two Canadian, five American). Patients were randomly assigned to one of three treatment groups (4 g 5-ASA, 2 g 5-ASA or placebo). Medication was dispensed as 250 mg identically appearing tablets containing either 5-ASA or placebo to be taken four times a day. Subjects were assessed at baseline and after three and six weeks of treatment. Assessments included a disease activity index, physician's global assessment and flexible sigmoidoscopy. Compliance was assessed through pill count. A total of 136 patients participated ( 4 7 on 4 g 5-ASA, 45 on 2 g 5-ASA, and 44 on placebo). The three groups were similar in terms of age, weight, distribution of disease, extent of disease, and previous use of steroids or sulphasalazine. Ninety patients completed the six week study. Of the 46 dropouts, 38 (82.6%) left because of insufficient efficacy ( most on either place ho or 2 g 5-ASA), four (8.7%) had adverse reactions (all on 5-ASA), the remaining four (8.7%) left for reasons not related to their ulcerative colitis. The disease activity index represents a composite score ( maximum of 12) with categories for number of daily stools, presence of bleeding, abdominal pain and physician's assessment of disease activity. Patients who received 4 g 5-ASA daily demonstrated significant declines in disease activity index within three weeks of therapy and maintained improvement until the end of the stuuy. Although disease activity index declined for patients receiving 2 g 5-ASA daily, these changes did not reach statistical significance when compared to placebo-treated patients. On a five point scale (much improved, somewhat improved, unchanged, somewhat worse, much worse) the physician's global assessment mirrored the changes in disease activity index. Patients randomized to receive 4 g 5-ASA tablets were consistently noted as being either much or somewhat improved compared to placebo-treated patients. Side effects were few and minor and 52% (4 g 5-ASA), 42% (2 g 5-ASA) and 37% (placebo) of patients had no complaints. Headache was the most commonly cited adverse reaction for 6.9% (4 g 5-ASA) and 9.4% (2 g 5-ASA) of treated patients but 3.5% of placebo-treated patients also complained of headache. In conclusion in this randomized double-blind, placebo controlled study, patients with active ulcerative colitis randomized to 4 g 5-ASA per day noted improvement in disease activity as measured by disease activity index and physician's global assessment when compared to placebo-treated patients. ln contrast, patients who received 2 g 5-ASA daily did not demonstrate significant differences compared to the placebo group.

P113 STUDY OF THE PROTEOMIC PROFILE IN PATIENTS WITH ULCERATIVE COLITIS, ITS CORRELATION WITH DIAGNOSIS AND DISEASE ACTIVITY

2018 ◽  
Vol 154 (1) ◽  
pp. S58
Author(s):  
Salah Badr El-Din ◽  
Ezzat Ali ◽  
Doaa Header ◽  
Pacint Moez ◽  
Mohamed Ibrahim
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Proteomic Profile

Disease activity, pANCA and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis

2009 ◽  
Vol 47 (09) ◽  
Author(s):  
M Jürgens ◽  
R Laubender ◽  
F Hartl ◽  
M Weidinger ◽  
J Wagner ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Early Response

scholarly journals Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Öhman ◽  
Anders Lasson ◽  
Anna Strömbeck ◽  
Stefan Isaksson ◽  
Marcus Hesselmar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Temporal Dynamics ◽  
Fecal Microbiota ◽  
Disease Stage ◽  
Dietary Interventions ◽  
Microbial Composition ◽  
Fecal Samples ◽  
Specific Species

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

scholarly journals Mobile App-based documentation of patient-reported outcomes — 3-months results from a proof-of-concept study on modern rheumatology patient management

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jutta G. Richter ◽  
Christina Nannen ◽  
Gamal Chehab ◽  
Hasan Acar ◽  
Arnd Becker ◽  
...  
Keyword(s):  
Disease Activity ◽  
Disease Surveillance ◽  
Patient Management ◽  
Activity Index ◽  
Retention Rate ◽  
Likert Scale ◽  
Mobile App ◽  
Proof Of Concept ◽  
Concept Study ◽  
Patient Reported

Abstract Background Mobile medical applications (Apps) offer innovative solutions for patients’ self-monitoring and new patient management opportunities. Prior to routine clinical application feasibility and acceptance of disease surveillance using an App that includes electronic (e) patient-reported outcome measures (PROMs) warrant evaluation. Therefore, we performed a proof-of-concept study in which rheumatoid arthritis (RA) patients used an App (RheumaLive) to document their disease. Methods Accurate PROM reporting via an App in comparison to paper-based versions was investigated to exclude media bias. Sixty participants recruited from 268 consecutive RA outpatients completed paper-based and electronic PROMs (Hannover Functional Questionnaire/derived HAQ; modified RA disease activity index) using the App at baseline and follow-up visits. Between visits, patients used their App on their own smartphone according to their preferences. The equivalence of PROM data and user experiences from patients and physicians were evaluated. Results Patients’ (78.3% female) mean (SD) age was 50.1 (13.1) years, disease duration 10.5 (9.1) years, and paper-based HAQ 0.78 (0.59). Mean confidence in Apps scored 3.5 (1.1, Likert scale 1 to 6). ePROMs’ scores obtained by patients’ data entry in the App were equivalent to paper-based ones and preferred by the patients. After 3 months, the App retention rate was 71.7%. Patients' overall satisfaction with the App was 2.2 (0.9, Likert scale 1 to 6). Patients and physicians valued the App, i.e., for patient-physician interaction: 87% reported that it was easier for them to document the course of the disease using the App than “only” answering questions about their current health during routine outpatient visits. Further App use was recommended in 77.3% of the patients, and according to physicians, in seven patients, the App use contributed to an increased adherence to therapy. Conclusion Our study provides an essential basis for the broader implementation of medical Apps in routine care. We demonstrated the feasibility and acceptance of disease surveillance using a smartphone App in RA. App use was convincing as a reliable option to perform continuous, remote monitoring of disease activity and treatment efficacy. Trial registration ClinicalTrials.gov, NCT02565225. Registered on September 16, 2015 (retrospectively registered).

scholarly journals Switching from TNFα inhibitor to tacrolimus as maintenance therapy in rheumatoid arthritis after achieving low disease activity with TNFα inhibitors and methotrexate: 24-week result from a non-randomized, prospective, active-controlled trial

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Sang Youn Jung ◽  
Jung Hee Koh ◽  
Ki-Jo Kim ◽  
Yong-Wook Park ◽  
Hyung-In Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Maintenance Therapy ◽  
Disease Activity ◽  
Controlled Trial ◽  
Tumor Necrosis Factor Inhibitor ◽  
Controlled Study ◽  
Open Label ◽  
Low Disease Activity ◽  
Efficacy Analysis ◽  
Tnfα Inhibitor

Abstract Background Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). Methods This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. Results In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01–1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. Conclusion This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. Trial registration Korea CDC CRIS, KCT0005868. Registered 4 February 2021—retrospectively registered

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