Medical therapy of ulcerative proctitis and proctosigmoiditis, including refractory disease

Bitton, Alain; Peppercorn, Mark A.

doi:10.1002/ibd.3780010308

Cited by 8 publications

(5 citation statements)

References 128 publications

(44 reference statements)

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“…The extension of ulcerative colitis (UC) is variable; it can be confined to the rectum (proctitis), can involve the colonic mucosa up to the left flexure (proctosigmoiditis), or can extend above the left flexure (extensive colitis). Colitis confined to the distal colon only is characterized by a milder clinical course, and the patients generally are more responsive to therapy than patients with extensive colitis 1. The factors determining the extension and degree of activity of the mucosal inflammation are largely unknown.…”

mentioning

confidence: 99%

Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity

Holmén

Lundgren

Lundin

et al. 2006

Inflammatory Bowel Diseases

163

124

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mentioning

confidence: 99%

Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity

Holmén

Lundgren

Lundin

et al. 2006

Inflammatory Bowel Diseases

163

124

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“…The daily dose is then reduced by 10 mg each week until it becomes a dose of 20 mg each day, at which time it is reduced by 5 mg per week until zero. 37 Table 1 is an algorithm for the treatment of ulcerative proctitis.…”

Section: Refractory Diseasementioning

confidence: 99%

Ulcerative Proctitis

Whitlow

2004

Clinics in Colon and Rectal Surgery

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Ulcerative proctitis is an idiopathic mucosal inflammatory disease involving only the rectum and is therefore an anatomically limited form of ulcerative colitis. Diagnosis is made based on clinical presentation, endoscopic appearance, and histopathology. Additionally, other etiologies of proctitis are excluded. The course of the disease is variable ranging from complete resolution to easily maintained remission to frequent relapses or refractory disease. Extension of inflammatory changes involving the proximal colon occurs in some cases. Rectal 5-aminosalicylic acid (5-ASA) or steroids are the initial treatments of choice with oral 5-ASA, sulfasalazine, or steroids used for treatment failures or patients unable to tolerate rectally administered drugs. Immunomodulators like azathioprine and 6-mercaptopurine have been used successfully in small groups of patients who have not responded to 5-ASA or steroids. Oral or rectal 5-ASA products maintain remission but long-term steroid use should be avoided. Rare cases may require surgical therapy.

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“…The dysregulated immune responses and inflammatory flares experienced in IBD result in severe abdominal pain, diarrhea, and rectal bleeding, which if left untreated can lead to malnutrition, increased risk of colorectal cancer, and the need for intestinal resection of fibrotic lesions. 8 -10…”

Section: Introductionmentioning

confidence: 99%

Nonclinical Toxicology and Toxicokinetic Profile of an Oral Lanthionine Synthetase C-Like 2 (LANCL2) Agonist, BT-11

Leber¹,

Hontecillas²,

Zoccoli-Rodriguez³

et al. 2019

Int J Toxicol

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BT-11 is an orally active, gut-restricted investigational therapeutic targeting the lanthionine synthetase C-like 2 pathway with lead indications in ulcerative colitis (UC) and Crohn disease (CD), 2 manifestations of inflammatory bowel disease (IBD). In 5 mouse models of IBD, BT-11 is effective at oral doses of 8 mg/kg. BT-11 was also efficacious at nanomolar concentrations in primary human samples from patients with UC and CD. BT-11 was tested under Good Laboratory Practice conditions in 90-day repeat-dose general toxicity studies in rats and dogs, toxicokinetics, respiratory, cardiovascular and central nervous system safety pharmacology, and genotoxicity studies. Oral BT-11 did not cause any clinical signs of toxicity, biochemical or hematological changes, or macroscopic or microscopic changes to organs in 90-day repeat-dose toxicity studies in rats and dogs at doses up to 1,000 mg/kg/d. Oral BT-11 resulted in low systemic exposure in both rats (area under the curve exposure from t = 0 to t = 8 hours [AUC0-8] of 216 h × ng/mL) and dogs (650 h × ng/mL) and rapid clearance with an average half-life of 3 hours. BT-11 did not induce changes in respiratory function, electrocardiogram parameters, or behavior with single oral doses of 1,000 mg/kg/d. There was no evidence of mutagenic or genotoxic potential for BT-11 up to tested limit doses using an Ames test, chromosomal aberration assay in human peripheral blood lymphocytes, or micronucleus assay in rats. Therefore, nonclinical studies show BT-11 to be a safe and well-tolerated oral therapeutic with potential as a potent immunometabolic therapy for UC and CD with no-observed adverse effect level >1,000 mg/kg in in vivo studies.

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Medical therapy of ulcerative proctitis and proctosigmoiditis, including refractory disease

Cited by 8 publications

References 128 publications

Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity

Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity

Ulcerative Proctitis

Nonclinical Toxicology and Toxicokinetic Profile of an Oral Lanthionine Synthetase C-Like 2 (LANCL2) Agonist, BT-11

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