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The American Journal of Gastroenterology Nov 2023Bowel urgency (BU), the sudden or immediate need for a bowel movement, is one of the most common and disruptive symptoms experienced by patients with ulcerative colitis... (Review)
Review
Bowel urgency (BU), the sudden or immediate need for a bowel movement, is one of the most common and disruptive symptoms experienced by patients with ulcerative colitis (UC). Distinct from the separate symptom of increased stool frequency, BU has a substantial negative impact on quality of life and psychosocial functioning. Among patients with UC, BU is one of the top reasons for treatment dissatisfaction and one of the symptoms patients most want improved. Patients may not discuss BU often due to embarrassment, and healthcare providers may not address the symptom adequately due to the lack of awareness of validated tools and/or knowledge of the importance of assessing BU. The mechanism of BU in UC is multifactorial and includes inflammatory changes in the rectum that may be linked to hypersensitivity and reduced compliance of the rectum. Responsive and reliable patient-reported outcome measures of BU are needed to provide evidence of treatment benefits in clinical trials and facilitate communication in clinical practice. This review discusses the pathophysiology and clinical importance of BU in UC and its impact on the quality of life and psychosocial functioning. Patient-reported outcome measures developed to assess the severity of BU in UC are discussed alongside overviews of treatment options and clinical guidelines. Implications for the future management of UC from the perspective of BU are also explored.
Topics: Humans; Colitis, Ulcerative; Quality of Life; Rectum; Patient Reported Outcome Measures
PubMed: 37436151
DOI: 10.14309/ajg.0000000000002404 -
Clinical Gastroenterology and... Aug 2023We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis...
BACKGROUND & AIMS
We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). Post hoc analyses were performed on pooled data from 2 replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH, to determine the earliest time point of efficacy onset.
METHODS
Diary entry data through 14 days from the first dose of placebo or upadacitinib 45 mg QD were analyzed for daily improvement in UC symptoms (stool frequency, rectal bleeding, abdominal pain, and bowel urgency). Changes in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin (FCP) were assessed at week 2 and quality of life (QoL) at weeks 2 and 8. Regression analysis determined the association between changes in UC symptoms and the likelihood of achieving clinical remission/response per Adapted Mayo score at week 8.
RESULTS
Overall, 988 patients (n = 328 placebo, n = 660 upadacitinib) were analyzed. Patients treated with upadacitinib demonstrated significant improvements vs placebo in all UC symptoms between days 1 and 3 and maintained through day 14. A >50% reduction from baseline in hs-CRP and FCP levels was achieved by 75.7% and 48.2% of patients, respectively (P < .001 vs placebo). Increased rates of clinical remission/response per Partial Mayo score from week 2 (26.9%/59.4% upadacitinib 45 mg QD vs 4.3%/22.3% placebo, P < .001) and significant improvements in QoL at weeks 2 and 8 were observed. Early improvement in stool frequency and bowel urgency by day 3 and reductions in hs-CRP and FCP by week 2 were significantly associated with clinical remission/response at week 8.
CONCLUSIONS
Upadacitinib 45 mg QD provided rapid relief of UC symptoms from day 1.
CLINICALTRIALS
gov: U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026).
Topics: Humans; Colitis, Ulcerative; Quality of Life; C-Reactive Protein; Heterocyclic Compounds, 3-Ring; Treatment Outcome; Double-Blind Method
PubMed: 36464141
DOI: 10.1016/j.cgh.2022.11.029 -
Annals of Gastroenterological Surgery Sep 2023Low anterior resection syndrome (LARS) is the distressful defecatory functional problem after sphincter-saving surgery for rectal cancer. Although the symptoms of fecal... (Review)
Review
Low anterior resection syndrome (LARS) is the distressful defecatory functional problem after sphincter-saving surgery for rectal cancer. Although the symptoms of fecal urgency, frequency, and incontinence may develop in most of the patients after surgery, there is no definitive treatments for LARS. Multifactorial etiologies and various risk factors have been identified, but the reduction of storage capacity in the rectum is one of the main reasons for LARS. Anal sphincter muscle or nerve damage during rectoanal resection or anastomosis construction, and intersphincteric resection for low-lying tumors or hand-sewing anastomosis, are the absolute risk factors for LARS. Preoperative radiotherapy, postoperative complications, such as anastomosis leakage, or longer duration of stoma, are also risk factors. The severity of LARS can be confirmed using the LARS score questionnaire. The questionnaire has been translated to numerous language versions including Korean and have been validated. Diverse empirical treatments, such as loperamide, fiber, probiotics, or enema, have been tried, but the safety and efficacy have not been verified yet. The 5-Hydroxytryptamine (5-HT) receptor antagonist, ramosetron, used for diarrhea-dominant irritable bowel syndrome, is one potential drug for relieving the symptoms of major LARS. A randomized-controlled trial suggested the use of ramosetron could be safe and efficacious for patients who have major LARS after sphincter-saving rectal cancer surgery. Novel techniques or drugs for relieving the symptoms of LARS should be developed more and further studies are necessary.
PubMed: 37663958
DOI: 10.1002/ags3.12695 -
Clinical Gastroenterology and... Jun 2023Fecal urgency, which is defined by the sudden need to rush to the bathroom to empty one's bowel, is one of the common and distressing symptoms experienced by patients... (Review)
Review
BACKGROUND & AIMS
Fecal urgency, which is defined by the sudden need to rush to the bathroom to empty one's bowel, is one of the common and distressing symptoms experienced by patients with inflammatory bowel disease.
METHODS
We performed a narrative review to investigate the definition, pathophysiology, and therapeutic management of fecal urgency.
RESULTS
Definitions of fecal urgency in inflammatory bowel disease, but also in irritable bowel syndrome, oncology, nononcologic surgery, obstetrics and gynecology, and in proctology, are empirical and heterogenous, lacking standardization. In the majority of these studies, nonvalidated questionnaires were used. When nonpharmacologic measures (dietary regimen, cognitive behavioral program) fail, medications such as loperamide, tricyclic antidepressants, or biofeedback therapy may become necessary. Medical management of fecal urgency may be challenging, in part because only limited data are available regarding the treatment of this symptom in randomized clinical trials of biologics in patients with inflammatory bowel disease.
CONCLUSIONS
There is an urgent need for a systematic approach to assessment of fecal urgency in inflammatory bowel disease. It is time to consider fecal urgency as an outcome in clinical trials to remedy this disabling symptom.
Topics: Pregnancy; Female; Humans; Inflammatory Bowel Diseases; Fecal Incontinence; Irritable Bowel Syndrome; Surveys and Questionnaires; Colitis, Ulcerative
PubMed: 36906079
DOI: 10.1016/j.cgh.2023.02.029 -
Journal of Crohn's & Colitis Oct 2023To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC].
METHODS
Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR.
RESULTS
Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p <0.001], irrespective of prior biologic/tofacitinib failure [p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p <0.05]; ER at W12 was associated with clinical remission [CR] [p <0.05] and corticosteroid-free remission [CSFR] at W40 [p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [p <0.05].
CONCLUSIONS
Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.
Topics: Humans; Female; Colitis, Ulcerative; Inflammation; Adrenal Cortex Hormones; Biological Products; Remission Induction; Sulfonamides; Antibodies, Monoclonal, Humanized
PubMed: 37057827
DOI: 10.1093/ecco-jcc/jjad050 -
The Korean Journal of Gastroenterology... Apr 2024Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD... (Review)
Review
Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1-2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.
Topics: Humans; Diarrhea; Bile Acids and Salts
PubMed: 38659249
DOI: 10.4166/kjg.2023.119 -
Inflammatory Bowel Diseases Nov 2023This post hoc analysis of a large, phase 3 program evaluated the effects of upadacitinib on fatigue, bowel urgency, and abdominal pain in patients with moderately to...
Upadacitinib Induction and Maintenance Therapy Improves Abdominal Pain, Bowel Urgency, and Fatigue in Patients With Ulcerative Colitis: A Post Hoc Analysis of Phase 3 Data.
BACKGROUND
This post hoc analysis of a large, phase 3 program evaluated the effects of upadacitinib on fatigue, bowel urgency, and abdominal pain in patients with moderately to severely active ulcerative colitis.
METHODS
Induction data were pooled from 2 identical studies, the U-ACHIEVE induction and U-ACCOMPLISH studies. Patients in these studies received upadacitinib 45 mg once daily or placebo as induction treatment. Responders to induction treatment were rerandomized in the U-ACHIEVE maintenance study to upadacitinib 15 mg once daily, upadacitinib 30 mg, or placebo. The percentage of patients reporting no abdominal pain and no bowel urgency daily via an electronic diary and a meaningful within-person change (≥5 points) in the Functional Assessment of Chronic Illness Therapy-Fatigue score were evaluated.
RESULTS
The results demonstrated a statistically significantly greater percentage of patients reporting no abdominal pain and absence of bowel urgency observed from week 2 (P < .001), with upadacitinib induction treatment and clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue score observed at week 8 (P < .001), when compared with placebo. The maintenance study showed that significant and meaningful improvements in abdominal pain, bowel urgency, and Functional Assessment of Chronic Illness Therapy-Fatigue score achieved during induction were sustained through 52 weeks of maintenance treatment in upadacitinib- vs placebo-treated patients.
CONCLUSIONS
The findings of this study support the additional benefit of upadacitinib in treating moderately to severely active ulcerative colitis by demonstrating a statistically significant impact on clinically meaningful symptoms of fatigue, bowel urgency, and abdominal pain.(U-ACHIEVE induction and maintenance studies; NCT02819635; U-ACCOMPLISH induction study; NCT03653026).
Topics: Humans; Abdominal Pain; Chronic Disease; Colitis, Ulcerative; Double-Blind Method; Heterocyclic Compounds, 3-Ring; Treatment Outcome
PubMed: 36790041
DOI: 10.1093/ibd/izad016