scholarly journals Pharmacokinetics, Pharmacodynamics, and Safety of Etrolizumab in Children With Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease: Results from a Phase 1 Randomized Trial

2021 ◽  
Author(s):  
Wenhui Zhang ◽  
Astrid Scalori ◽  
Franklin Fuh ◽  
Jacqueline McBride ◽  
Gaohong She ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase 1 ◽  
Receptor Occupancy ◽  
Clinical Activity ◽  
Active Ulcerative Colitis ◽  
Open Label ◽  
Proportional Increase ◽  
Dose Proportional

Abstract Background Etrolizumab, a humanized anti-β7 antibody, has not been studied in children. Here, we evaluate the pharmacokinetics, pharmacodynamics, and safety of etrolizumab in children with inflammatory bowel disease. Methods Patients age 4 to 17 years with moderately to severely active ulcerative colitis or Crohn’s disease were randomized 1:1 to receive 1.5mg/kg of etrolizumab subcutaneously every 4 weeks (q4w) or 3.0mg/kg every 8 weeks (q8w) for 16 weeks in this open-label phase 1 trial. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed. Results Of the 24 patients treated, 21 completed the study. In the groups of 1.5mg/kg q4w and 3.0mg/kg q8w, respectively, mean (SD) maximum concentration (Cmax) was 9.8 (4.86) µg/mL and 18.1 (6.25) µg/mL; and mean (SD) area under the curve within a dosing interval (AUCtau) was 167 (86.9) and 521 (306) μg·day/mL after the last dose. The Cmax increased dose proportionally. The AUC over an 8-week period was slightly higher in the 3.0mg/kg q8w dose group. Median half-life was similar for both dosing regimens. Median numbers of free β7high gut-homing T and B cell subsets declined below 10% of baseline, confirming β7 target engagement and complete/near-complete receptor occupancy. Adverse events were consistent with the safety profile in adults. Approximately 60% of patients achieved a clinical response. Conclusions Etrolizumab showed a dose-proportional increase in Cmax and a slightly greater than dose-proportional increase in AUCtau. Both regimens achieved complete/near-complete β7 receptor occupancy, with a similar relationship to concentration as adults. Etrolizumab was well tolerated and demonstrated clinical activity in children.

Psychologic Stress in Crohn's Disease an Ulcerative Colitis: Role of Gender and Clinical Activity of the Disease

2011 ◽  
Vol 140 (5) ◽  
pp. S-787
Author(s):  
Marta Iglesias-Rey ◽  
Manuel Barreiro-de Acosta ◽  
Isabel Vazquez ◽  
Maria Piñeiro ◽  
Adolfo Figueiras ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Activity ◽  
Psychologic Stress

The Effect of Mesalamine and Nicotine in the Treatment of Inflammatory Bowel Disease

1997 ◽  
Vol 31 (7-8) ◽  
pp. 907-913 ◽  
Author(s):  
Charles R. Bonapace ◽  
David A. Mays
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Relapse Rate ◽  
Bowel Disease ◽  
Therapeutic Agent ◽  
Active Ulcerative Colitis ◽  
Steroid Dependence ◽  
Inflammatory Bowel

OBJECTIVE: To characterize the usefulness of mesalamine and nicotine in the treatment of active ulcerative colitis and inactive Crohn's disease. DATA SOURCES: Citations were selected from the MEDLINE database. Only those involving human subjects, inflammatory bowel disease, and available in English were selected. STUDY SELECTION: Selection criteria consisted of clinical trials and review articles assessing the effects of mesalamine and nicotine in active ulcerative colitis or inactive Crohn's disease and the utility of reducing steroid dependence or relapse rate. Less than 20% of the articles identified met the selection criteria. DATA SYNTHESIS: In patients with inactive Crohn's disease, mesalamine 2 g/d significantly reduced the risk of relapse in high-relapse-risk patients compared with placebo, reducing the relapse rate from 71% to 55%, but was ineffective in preventing recurrence of inactive Crohn's disease following surgical resection. Mesalamine 4 g/d was effective in decreasing weaning failure due to steroid dependence by 67%, although the relapse rate was not significant compared with placebo at the end of 12 months. Following surgical resection, mesalamine was unable to significantly reduce the incidence of recurrence compared with placebo at the end of 1 year. In patients with active ulcerative colitis, oral mesalamine 2 and 4 g/d was superior to placebo in inducing remission compared with placebo. Among patients with prior steroid or sulfasalazine treatment, rectal mesalamine 4 g hs achieved a remission rate of 78% in more than 12 weeks of therapy. Other studies have not found a dose—response relationship with lower dosages of mesalamine. Whereas nicotine 15–25 mg/d administered as a transdermal patch produced greater symptomatic improvement in active ulcerative colitis compared with placebo, nicotine 15 mg/16 h produced results no different from those with placebo in maintaining remission in inactive ulcerative colitis. Nicotine appears to have an adverse effect on the course of Crohn's disease and is not recommended. CONCLUSIONS: Mesalamine has demonstrated clinical effectiveness as a therapeutic agent in the treatment of active ulcerative colitis and inactive Crohn's disease. Although its relationship to inflammatory bowel disease has been known for many years, the usefulness of nicotine for the treatment of active ulcerative colitis requires further exploration before it can be recommended as a therapeutic agent.

A New Type of Perinuclear Anti-Neutrophil Cytoplasmic Antibody (p-ANCA) in Active Ulcerative Colitis but not in Crohn's Disease

Immunobiology ◽  
1990 ◽  
Vol 181 (4-5) ◽  
pp. 406-413 ◽  
Author(s):  
Jörg A. Rump ◽  
Jürgen Schölmerich ◽  
Volker Gross ◽  
Michael Roth ◽  
Renate Helfesrieder ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Active Ulcerative Colitis ◽  
New Type

scholarly journals Dynamics of leukocytic blood parameters depending on the activity of inflammatory bowel disease in children

2021 ◽  
Vol 24 (3) ◽  
pp. 148-156
Author(s):  
Elena L. Semikina ◽  
Valeriya S. Tsvetkova ◽  
Alexander S. Potapov ◽  
Elena A. Kopyltsova ◽  
Andrey P. Fisenko ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Absolute Number ◽  
Blood Parameters ◽  
Clinical Activity ◽  
Inflammatory Bowel ◽  
The Absolute

Aim: to establish the patterns of changes in leukocyte blood parameters to determine their diagnostic significance in the different activity of Crohn’s disease (CD) and ulcerative colitis (UC) in children. Materials and methods. 370 5-18-year children (198 boys, 172 girls) with inflammatory bowel disease (IBD) were examined. Leukocytic blood parameters, concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), faecal calprotectin (FC) levels were determined. Changes in clinical activity in Crohn’s disease (CD) and ulcerative colitis (UC) cases were determined using pediatric activity indices: PCDAI and PUCAI, respectively. Analysis of endoscopic activity in 160 CD and UC patients was determined using the scales: SES-CD and UCEIS, respectively. Results. It was found that with an increase in the clinical activity of CD in children, the absolute numbers of leukocytes, lymphocytes and monocytes did not change significantly. In contrast, a significant increase in neutrophil reactivity was noted. In patients with high endoscopic CD activity an increase in the absolute number of monocytes and neutrophil reactivity was found. In patients with high clinical activity of UC, an increase in the number of leukocytes and the absolute number of neutrophils was found. At the same time, the granularity and reactivity of neutrophils increased from remission to moderate and high clinical activity of UC. In children with high endoscopic UC activity, the number of leukocytes, the absolute number of neutrophils and monocytes increased. At the same time, the granularity of neutrophils significantly increased as the endoscopic activity of UC increased from remission to moderate activity. Leukocyte parameters in UC patients correlated moderately with FC level, and the absolute number of neutrophils was closely related to its content. The granularity and reactivity of neutrophils positively correlated with ESR and CRP levels in children with CD and CRP concentrations in children with UC. Conclusion. The established patterns of changes in the quantitative composition of leukocytes and their functional properties (reactivity and granularity) are directly determined by the different activity of IBD in children and have diagnostic value

Use of helminth therapy for management of ulcerative colitis and Crohn's disease: a systematic review

Parasitology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Victoria Emma Shields ◽  
Jan Cooper
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Placebo Effect ◽  
Developed Countries ◽  
Cochrane Central Register ◽  
Open Label ◽  
Double Blind ◽  
Helminth Therapy

Abstract The incidence rate of inflammatory bowel diseases is increasing in developed countries. As such there is an increasing demand for new therapies. The aim of this systematic review was to investigate whether there is evidence to support the use of helminth therapy for the management of Crohn's disease and ulcerative colitis. Four databases (PubMed, Embase, Medline and the Cochrane Central Register of Control Trials) were searched for primary evidence in the form of clinical studies. Nine studies were suitable for inclusion: five double-blind randomized control trials and four open-label studies. This review divided the results of the studies into two categories: (a) the efficacy of helminth therapy and (b) the safety of helminth therapy. Results regarding the efficacy were mixed and a conclusive answer could not be reached, as there was not enough evidence to rule out a placebo effect. More research is needed, particularly studies with control groups to address the possibility of a placebo effect. Despite this, all nine studies concluded helminth therapy was safe and tolerable, and therefore there is currently no evidence against further exploration of this treatment option.

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