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

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.

Author(s):  
Wenhui Zhang ◽  
Astrid Scalori ◽  
Franklin Fuh ◽  
Jacqueline McBride ◽  
Gaohong She ◽  
...  

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.


2018 ◽  
Vol 107 (3) ◽  
pp. 189-196 ◽  
Author(s):  
T. Rasmussen ◽  
S. Fonnes ◽  
J. Rosenberg

Background and Aims: Appendectomy is a common surgical procedure, but no overview of the long-term consequences exists. Our aim was to systematically review the long-term complications of appendectomy for acute appendicitis. Materials and Methods: This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A protocol was registered on PROSPERO (CRD42017064662). The databases PubMed and EMBASE were searched for original reports on appendectomy with n ≥ 500 and follow-up >30 days. The surgical outcomes were ileus and incisional hernia; other outcomes were inflammatory bowel disease, cancer, fertility, and mortality. Results: We included 37 studies. The pooled estimate of the ileus prevalence was 1.0% over a follow-up period of 4.6 (range, 0.5–15) years. Regarding incisional hernia, we found a pooled estimate of 0.7% prevalence within a follow-up period of 6.5 (range, 1.9–10) years. Ulcerative colitis had a pooled estimate of 0.15% prevalence in the appendectomy group and 0.19% in controls. The opposite pattern was found regarding Crohn’s disease with a pooled estimate of 0.20% prevalence in the appendectomy group and 0.12% in controls. No clear pattern was found regarding most of the examined cancers in appendectomy groups compared with background populations. Pregnancy rates increased after appendicitis compared with controls in most studies. Mortality was low after appendectomy. Conclusion: Appendectomy had a low prevalence of long-term surgical complications. We did not find any significant other long-term complications, though the prevalence of Crohn’s disease was higher and the prevalence of ulcerative colitis was lower after appendectomy than in controls. Appendectomy did not impair fertility.


Author(s):  
Ricardo de Alvares Goulart ◽  
Sandra M. Barbalho ◽  
Vinícius Marinho Lima ◽  
Gabriela Achete de Souza ◽  
Julia Novaes Matias ◽  
...  

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
Geert R A M D’Haens ◽  
Neal Slatkin ◽  
Robert Israel ◽  
Zeev Heimanson

Abstract Background Anti-TNF agents are an established treatment modality for ulcerative colitis (UC); however, as many as 30% of patients do not respond to anti-TNF agents, and almost 50% of responders lose clinical benefits after a year of treatment. Furthermore, numerous safety concerns are associated with long-term use of anti-TNF agents. An alternative treatment in development for autoimmune-mediated diseases, including Crohn’s disease (CD) and UC, are sphingosine 1-phosphate receptor modulators such as amiselimod (AMS). Methods The safety and efficacy of oral AMS 0.4 mg/d in adults with moderate to severe active CD over 14 wks were evaluated in a multicenter, randomized, double-blind, parallel-group, placebo (PBO)-controlled (DBPC), phase 2a clinical trial, followed by an open-label extension (OLE) study with AMS for up to 36 wks. Patients had previously used anti-TNF-α agents, immunosuppressants, or corticosteroids. Safety data (adverse events [AEs]) were stratified by patients with and without prior anti-TNF treatment. Results Of the 78 patients randomized 1:1 to receive AMS (n=40) or PBO (n=38), 78% (n=61) completed the DBPC treatment phase. Of those patients continuing into the OLE, 26 patients (AMS/AMS [n=14]; PBO/AMS [n=12]) completed it. Oral AMS 0.4 mg for 12 wks did not have a significant effect on clinical disease activity in CD. Patients previously treated with anti-TNF agents had more serious AEs (SAEs) (27% AMS [n=22]; 4% PBO [n=25]) than did patients without prior anti-TNF treatment (0 AMS and 0 PBO patients). Relative numbers of treatment-emergent AEs (TEAEs) were similar between groups receiving prior anti-TNF agents (68% AMS [n=22]; 68% PBO [n=25]) and no prior treatment (65% AMS [n=17]; 31% PBO [n=13]). There was a trend toward more mild TEAEs and less severe AEs in patients not previously treated with anti-TNF agents compared to those previously treated. Conversely, in the OLE, patients not previously treated with anti-TNF agents had more AEs (100% AMS/AMS [n=11]; 67% PBO/AMS [n=9]) than those with prior treatment (60% AMS/AMS [n=10]; 87% PBO/AMS [n=16]). All of these TEAEs were mild or moderate. In the OLE, only 1 patient receiving AMS/AMS with no prior anti-TNF treatment had an SAE versus no patients with prior treatment. Conclusions Previous treatment with anti-TNF agents did not significantly affect the TEAEs associated with AMS. While SAEs appeared to be more common in previously treated patients in the DBPC, patients had fewer AEs during the OLE. This analysis suggests that previous treatment with anti-TNF agents should be considered when assessing the AE profile of AMS in future trials.


2012 ◽  
Vol 107 (S2) ◽  
pp. S240-S252 ◽  
Author(s):  
Eduard Cabré ◽  
Míriam Mañosa ◽  
Miquel A. Gassull

Background & Aim: Despite their well known anti-inflammatory actions, the clinical usefulness of omega-3 PUFA in inflammatory bowel disease is controversial. We aimed to systematically review the available data on the performance of omega-3 PUFA as therapeutic agents in these patients. Methods: Electronic databases were systematically searched for RCT of fish oil or omega-3 PUFA therapy in both active and inactive ulcerative colitis or Crohn's disease, without limitation on either the length of therapy or the form it was given, including nutritional supplements and enteral formula diets. Eligible articles were assessed for methodological quality on the basis of the adequacy of the randomisation process, concealment of allocation, blinding of intervention and outcome, possible biases, and completeness of follow-up. The five-point Oxford quality score was calculated. Results: A total of 19 RCT were finally selected for this review. Overall, available data do not allow to support the use of omega-3 PUFA supplementation for the treatment of both active and inactive inflammatory bowel disease. Negative results are quite consistent in trials assessing the use of omega-3 PUFA to maintain disease remission, particularly ulcerative colitis, and to a lesser extent Crohn's disease. Trials on their use in active disease do not allow to draw firm conclusions mainly because the heterogeneity of design (ulcerative colitis) or their short number (Crohn's disease). In most trials, the appropriateness of the selected placebo is questionable. Conclusion: The present systematic review does not allow to make firm recommendations about the usefulness of omega-3 PUFA in inflammatory bowel disease.


2017 ◽  
Vol 15 (11) ◽  
pp. 1684-1697.e11 ◽  
Author(s):  
Andrea Iannone ◽  
Marinella Ruospo ◽  
Germaine Wong ◽  
Mariabeatrice Principi ◽  
Michele Barone ◽  
...  

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