scholarly journals Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn’s Disease: A Pilot Study (ACROHNEM)

2019 ◽  
Vol 9 (1) ◽  
pp. 41 ◽  
Author(s):  
Monique Capron ◽  
Laurent Béghin ◽  
Céline Leclercq ◽  
Julien Labreuche ◽  
Arnaud Dendooven ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Therapeutic Option ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Open Label ◽  
Th17 Response ◽  
Clinical Recurrence

Despite the development of novel therapies, inflammatory bowel diseases remain an innovative treatment challenge. Helminth therapy is a new promising approach, and a key issue is the identification of helminth-derived anti-inflammatory mediators. P28 glutathione-S-transferase (P28GST), a protein derived from schistosomes, a trematode parasitic helminth, was shown to reduce intestinal inflammation in experimental colitis by down-regulating the Th1/Th17 response. In this multicenter, open-label, pilot Phase 2a study, we evaluated the safety of P28GST administered to patients with mild Crohn’s disease (CD). We enrolled 10 patients with a baseline Crohn’s disease activity index (CDAI) value <220. Eight patients received two to three subcutaneous injections of recombinant P28GST with adjuvant. This three-month treatment was followed by a nine-month monitoring period. The primary endpoints were the monthly rate and seriousness of adverse events (AEs). Secondary endpoints were clinical recurrence, assessed with the CDAI as well as the levels of immunologic and inflammatory blood and tissue markers. The most common AEs were local or regional events at the injection site and gastrointestinal disorders. At three months after the first injection, CDAI scores and blood calprotectin levels decreased in parallel. These results indicate that P28GST showed promise as a safe and new therapeutic option for treating CD.

Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
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 ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

scholarly journals Efficacy and Safety of Adalimumab in Canadian Patients with Moderate to Severe Crohn’s Disease: Results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn’s DiseaSe (ACCESS) Trial

2011 ◽  
Vol 25 (8) ◽  
pp. 419-425 ◽  
Author(s):  
Remo Panaccione ◽  
Edward V Loftus ◽  
David Binion ◽  
Kevin McHugh ◽  
Shamsul Alam ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Patient Reported Outcomes ◽  
Activity Index ◽  
Work Productivity ◽  
Clinical Effectiveness ◽  
Open Label ◽  
Adalimumab Therapy ◽  
Patient Reported ◽  
Fistula Healing

OBJECTIVE: To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.METHODS: Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada.RESULTS: Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (P<0.01; P<0.001 for both groups for all visits versus baseline). Fistula healing rates at week 12 were 48% for anti-TNF-naive patients, and 26% for infliximab-experienced patients. At week 24, fistula healing rates were significantly greater for the anti-TNF-naive group (60% versus 28%; P<0.01). Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients. Serious infections occurred in 2% of patients.CONCLUSIONS: Adalimumab therapy induced and sustained steroid-free remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.

Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

2018 ◽  
Vol 56 (10) ◽  
pp. 1267-1275 ◽  
Author(s):  
Angelika Hüppe ◽  
Jana Langbrandtner ◽  
Winfried Häuser ◽  
Heiner Raspe ◽  
Bernd Bokemeyer
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Inflammatory Bowel ◽  
Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

scholarly journals Experiência clínica com o uso de infliximab em 44 portadores de doença de Crohn

2003 ◽  
Vol 40 (3) ◽  
pp. 198-200 ◽  
Author(s):  
Flavio Steinwurz
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Crohn’S Disease Activity

RACIONAL - OBJETIVO: Avaliar a eficácia do infliximab no tratamento de pacientes com doença de Crohn ativa ou com fístulas. MÉTODOS: Quarenta e quatro portadores de doença de Crohn, refratários ao tratamento convencional, foram tratados com infliximab, na dose de 5 mg/kg, através de infusão endovenosa. RESULTADOS: Trinta deles (68,2%) obtiveram melhora dos sintomas, com regressão importante nos níveis de atividade da doença, medidos pelo CDAI (Crohn's Disease Activity Index). Oito (57,1%) de 14 portadores de fístulas também obtiveram bons resultados, com fechamento ou importante diminuição do fluxo destas. A tolerância à droga foi boa em todos os casos. CONCLUSÃO: O uso de infliximab nestes casos parece ser boa opção terapêutica, com baixos índices de efeitos colaterais.

scholarly journals Fluticasone Propionate in Inflammatory Bowel Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 417-419 ◽  
Author(s):  
Marta Carpani de Kaski ◽  
Humphery JF Hodgson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Long Term Treatment ◽  
Systemic Side Effects ◽  
Inflammatory Bowel

Although effective for both acute and often long term treatment of inflammatory bowel disease, systemically absorbed corticosteroids have a high incidence of side effects. This article briefly reviews the pharmacokinetics of corticosteroids and the strategics available for reducing systemic side effects. In particular, fluitcasone propionate is a fluorinated glucocorticoid, in which systemic side effects are absent or minimal due to its relatively low absorption and rapid first pass metabolism In an open trial in 12 patients with mild and moderately active Crohn's disease, administration of 20 mg fluitcasone propionate orally was associated with a significant fall in the Crohn's disease activity index and improvement in other parameters of inflammation, without change in either plasma cortisol levels or responsiveness to adrenocorticotropic hormone, suggesting that this drug is a promising therapy for Crohn's disease meriting evaluation against conventional corticosteroids.

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