Overview of Biological Therapy in Ulcerative Colitis: Current and Future Directions

2015 ◽  
Vol 24 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Federica Furfaro ◽  
Cristina Bezzio ◽  
Sandro Ardizzone ◽  
Alessandro Massari ◽  
Roberto De Franchis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immunosuppressive Agents ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Proinflammatory Mediators ◽  
Experimental Drugs ◽  
New Treatments ◽  
Aggressive Clinical Course ◽  
Near Future

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

scholarly journals Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Kazuki Kakimoto ◽  
Minoru Matsuura ◽  
Takumi Fukuchi ◽  
Hitoshi Hongo ◽  
Tsuguhiro Kimura ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trial ◽  
Exploratory Study ◽  
Response Rate ◽  
Mucosal Healing ◽  
Prospective Clinical Trial ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Steroid Dependent ◽  
Adsorptive Apheresis

Abstract Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

scholarly journals Role of MicroRNAs in Human Osteosarcoma: Future Perspectives

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 463
Author(s):  
Lola Llobat ◽  
Olivia Gourbault
Keyword(s):  
Bone Cancer ◽  
Diagnostic Biomarkers ◽  
Regulate Gene Expression ◽  
High Death Rate ◽  
Different Types ◽  
High Death ◽  
New Treatments ◽  
Near Future ◽  
Cancer In Children

Osteosarcoma (OS) is a rare form of cancer with high death rate but is one of the most frequent forms of bone cancer in children and adolescents. MiRNAs are small endogenous RNAs that regulate gene expression post-transcriptionally. The discovery of miRNAs could allow us to obtain an earlier diagnosis, predict prognosis and chemoresistance, and lead to the discovery of new treatments in different types of tumors, including OS. Despite the fact that there is currently only one clinical trial being carried out on a single miRNA for solid tumors, it is very probable that the number of clinical trials including miRNAs as prognostic and diagnostic biomarkers, as well as potential therapeutic targets, will increase in the near future. This review summarizes the different miRNAs related to OS and their possible therapeutic application.

scholarly journals IMPORTANCE OF NANOCARRIERS AND PROBIOTICS IN THE TREATMENT OF ULCERATIVE COLITIS

2021 ◽  
pp. 77-85
Author(s):  
VANDANA THAKUR ◽  
BHUPENDRA SINGH ◽  
ANKITA SHARMA ◽  
NISHA KUMARI ◽  
INDER KUMAR ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Side Effects ◽  
Wide Spectrum ◽  
Gastrointestinal Diseases ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Bowel Distension ◽  
Inflammatory Reactions ◽  
Therapeutic Goals

Ulcerative colitis (UC) is an inflammatory chronic disease primarily affecting the colonic mucosa; the extent and severity of colon involvement are variable. Ulcerative colitis is identified by mucus diarrhea, tenesmus, bowel distension, and anemia. 5-aminosalicylic acid drugs, steroids, and immune suppressants are used for the therapy of ulcerative colitis. The mainchallenges in the management of thediseaseare drug-related side-effects and local targeting. To overcome these challengesprobiotics and micro and Nanoparticulate systemauspiciousapproaches to overcome drug-related adverse side effects and local targeting.Upon ingestion, the probiotics can result in beneficial health effects. Probiotics and micro and nanoparticulate approaches for suitable targeting and overcome the drug-associated side effect. Probiotics are mainly used as gut modulators but are also nowadays explored for their use in ulcerative colitis.The current therapeutic goals are to achieve clinical remission along with mucosal healing, avoidance of complications such as side effects of the drug and to improve the quality of life. The use of probiotics to increase the health of the intestine and used to block or manage intestinal disorders. They may prevent the induction of inflammatory reactions. Probiotics must be inspected for efficacy in the prevention and management of a wide spectrum of gastrointestinal diseases, like antibiotic-associated diarrhea.Micro and Nanoparticulate drug delivery system has been achieving huge importance for targeting of the drug to colon locally at a controlled and sustained rate.

scholarly journals Ulcerative colitis relapse after Helicobacter pylori eradication in a 12-year-old boy with duodenal ulcer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuji Fujita ◽  
Keiichi Tominaga ◽  
Takanao Tanaka ◽  
Takeshi Sugaya ◽  
Shigemi Yoshihara
Keyword(s):  
Ulcerative Colitis ◽  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Epigastric Pain ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Protective Role ◽  
Symptom Improvement ◽  
Aminosalicylic Acid ◽  
H Pylori

Abstract Background Helicobacter pylori (H. pylori) prevalence is lower in patients with inflammatory bowel disease (IBD) than in those without IBD, suggesting that H. pylori plays a protective role in IBD. It has been reported that IBD may occur due to H. pylori eradication; however, it is unclear whether H. pylori eradication increases the incidence of IBD. Moreover, the effect of H. pylori eradication on IBD activity is unclear. Case presentation An 11-year-old boy diagnosed with ulcerative colitis (UC) was in clinical remission, with treatment involving 5-aminosalicylic acid. Fecal calprotectin (FC) level had decreased to 33.2 mg/kg, indicating mucosal healing. At age 12, he experienced epigastric pain on an empty stomach, which was relieved with dietary intake. His FC level was elevated without UC symptoms, such as diarrhea and bloody stools. He was diagnosed with H. pylori duodenal ulcer. H. pylori eradication (clarithromycin and amoxicillin for 7 days and a proton-pump inhibitor) led to symptom improvement the day after treatment initiation. However, he developed diarrhea and his FC level remained high despite improvement in duodenal ulcer symptoms and endoscopic findings of H. pylori eradication. Colonoscopy results indicated UC relapse. Conclusions H. pylori eradication may worsen UC activity. However, further studies are required as this case report involved only one pediatric patient with increased UC activity after H. pylori eradication.

scholarly journals Mesalazine in Inflammatory Bowel Disease: A Trendy Topic Once Again?

2010 ◽  
Vol 24 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Marietta Iacucci ◽  
Shanika de Silva ◽  
Subrata Ghosh
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Peroxisome Proliferator ◽  
Aminosalicylic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission ◽  
Near Future

5-aminosalicylic acid (5-ASA) preparations (eg, mesalazine, mesalamine) are well-established preparations used in the management of inflammatory bowel disease. These drugs are most useful for the treatment of mild to moderate flares of ulcerative colitis and, especially, for maintenance of remission. Although most gastroenterologists are very familiar with these drugs, the interest in these drugs has undergone a resurgence, with new preparations offering convenience and high dosage, while preserving their customary safety. New dosage regimens are likely to become standard practice in the near future. There is also considerable interest in chemoprevention of colorectal cancer in the context of inflammatory bowel disease, and the role of long-term maintenance therapy with 5-ASAs in achieving such chemoprevention. A mechanism of action for such chemoprevention has been provided by the agonism of the peroxisome proliferator-activated receptor-gamma by 5-ASA, which unifies its efficacy as an anti-inflammatory and chemopreventive agent. In the future, even more effective agents based on 5-ASA are expected, based on more powerful agonism of peroxisome proliferator-activated receptor-gamma; 5-ASA preparations have become ‘trendy’ again.

scholarly journals Ketotifen Treatment of Active Colitis in Patients with 5-Aminosalicylate Intolerance

1998 ◽  
Vol 12 (4) ◽  
pp. 273-275 ◽  
Author(s):  
John K Marshall ◽  
E Jan Irvine
Keyword(s):  
Ulcerative Colitis ◽  
Mast Cell ◽  
Collagenous Colitis ◽  
Experimental Colitis ◽  
Aminosalicylic Acid ◽  
Mucosal Mast Cells ◽  
Active Colitis ◽  
Inflammatory Bowel ◽  
Allergic Disorders

Mast cell stabilizers are commonly used in the treatment of asthma and allergic disorders. Although the role of mucosal mast cells in the pathogenesis of inflammatory bowel disease remains uncertain, mast cell stabilizers have been shown in animal models to attenuate the severity of experimental colitis. The authors' experience with ketotifen in three patients - one each with Crohn's disease, ulcerative colitis and collagenous colitis - who had demonstrated allergy to, or intolerance of, 5-aminosalicylic acid is reported.

The Role of Combining Biochemical Markers in Assessing the Endoscopic Activity in Ulcerative Colitis

2018 ◽  
Vol 69 (5) ◽  
pp. 1268-1271
Author(s):  
Mihaela Dranga ◽  
Catalina Mihai ◽  
Otilia Gavrilescu ◽  
Anca Cardoneanu ◽  
Mariana Floria ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Linear Regression ◽  
Biochemical Markers ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Reactive Protein ◽  
Mayo Score ◽  
Inflammatory Bowel ◽  
A Prospective Study

Ulcerative colitis (UC) isa chronic, idiopathic and recurrent inflammatory bowel disease (IBD), characterized by periods of activity and remissionwhose monitoring requires invasive explorations associated with discomfort for the patient and important costs. Mucosal healing became one of the most important therapeutic targets in UC. The aim of our study was to identify a score, made up of noninvasive, available, used in current clinical practice biochemical markers, which should correlate with endoscopic activity in UC. We conducted a prospective study on 114 patients with UC. All patients were assessed both for biological inflammatory markers: erythrocyte sedimentation rate (ESR),C- reactive protein (CRP), fibrinogen, platelets, albumin, fecal calprotectin (FC) and by colonoscopy to estimate the endoscopic activity using Mayo score. By linear regression, we tried to identify a biochemical score correlated with endoscopic activity. Out of the serological markers,ESR (p=0.014), CRP(p= 0.021) and fibrinogen (p=0.035) correlated with the endoscopic activity of the disease. The best sensitivity to determine the endoscopic activity was given by FC (96.05%) with a predictable negative value of 91.1% (p=0.001). The score determined by linear regression: 1 (ESR]15mm/1h) x 0.305 + 1(fibrinogen]340.5mg/dL) x 0.309+1 (CRP] 5 mg/L) + 1 (calprotectin]200 μg/g) had an increased positive predictive value compared to each and one biomarker, nevertheless, with a sensitivity and specificity inferior to that of FC. Up to now, it is the first attempt to achieve a score made up exclusively of biological markers. The obtained score, although with an increased accuracy, has proven to have a lower predictability in comparison with FC used individually and cannot entirely replace colonoscopy.

scholarly journals Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kazuhiko Uchiyama ◽  
Tomohisa Takagi ◽  
Katsura Mizushima ◽  
Mariko Kajiwara-Kubota ◽  
Saori Kashiwagi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mrna Expression ◽  
Real Time Pcr ◽  
Mucosal Healing ◽  
Histological Activity ◽  
Ifn Γ ◽  
Rectal Biopsies ◽  
Relapse Group

Abstract Background The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. Methods Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. Results The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). Conclusions Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

scholarly journals Role of Quantitative Fecal Immunochemical Test in Assessment of Mucosal Healing in Patients with Ulcerative Colitis

2018 ◽  
Vol 86 (March) ◽  
pp. 589-595
Author(s):  
AHMAD F. ABO EL-EZZ AHMED, M.Sc. MOHAMED M. EL-BEDEWY, M.D. ◽  
MOHAMED A.S. ATTIA, M.D. MAHMOUD F. SELIM, M.D.
Keyword(s):  
Ulcerative Colitis ◽  
Mucosal Healing ◽  
Fecal Immunochemical Test ◽  
Immunochemical Test

scholarly journals Increased Mucosal IL-12 Expression is Associated with Relapse of Ulcerative Colitis

2021 ◽  
Author(s):  
Kazuhiko Uchiyama ◽  
Tomohisa Takagi ◽  
Katsura Mizushima ◽  
Mariko Kajiwara-Kubota ◽  
Saori Kashiwagi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mrna Expression ◽  
Real Time Pcr ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Histological Activity ◽  
Rectal Biopsies ◽  
Relapse Group

Abstract Background: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse.Methods: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-g, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. Results: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P=0.0003) and IL-23 (P=0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P=0.015) but not IL-12 (P=0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P=0.0015, P=0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P=0.0002, IL-23: P=0.046).Conclusions: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

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