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Randomised clinical study: discrepancies between patient-reported outcomes and endoscopic appearance in moderate to severe ulcerative colitis.

ABSTRACT: Associations between patient-reported outcomes and mucosal healing have not been established in ulcerative colitis (UC).To evaluate relationships of rectal bleeding and stool frequency with mucosal healing and quality of life (QoL) in patients with UC in two Phase 3 studies (ULTRA 1 and 2).Associations of patient-reported rectal bleeding and stool frequency subscores with mucosal healing (Mayo endoscopy subscore = 0 or 0/1) and QoL [inflammatory bowel disease questionnaire (IBDQ)] were assessed in adalimumab-randomised patients (160/80 mg at Weeks 0/2 followed by 40 mg biweekly or weekly) at Weeks 8 (n = 433) and 52 (n = 299), and in patients with mucosal healing [endoscopy subscore = 0 (n = 17); 0/1 (n = 52)] at Weeks 8 and 52.At Week 8, the positive predictive values (PPVs) of rectal bleeding subscore = 0, stool frequency subscore = 0 or both scores = 0 for endoscopy subscore = 0/1 were 69%, 84% and 90% respectively; all proportions increased at Week 52. Equivalent PPVs for these subscores in patients with endoscopy subscore = 0 were 26%, 37% and 46% respectively. Among patients with endoscopy subscore = 0 at Week 8, 87% reported no rectal bleeding, while only 29% reported normal stool frequency; these proportions had increased to 94% and 41% respectively, at Week 52. Among patients with mucosal healing, IBDQ scores trended highest for patients with both rectal bleeding and stool frequency subscores = 0.Absence of rectal bleeding and normal stool frequency are often predictive of mucosal healing and QoL, but complete normalisation of stool frequency is encountered rarely in patients with mucosal healing.

SUBMITTER: Jharap B

PROVIDER: S-EPMC5049645 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Randomised clinical study: discrepancies between patient-reported outcomes and endoscopic appearance in moderate to severe ulcerative colitis.

Jharap B B Sandborn W J WJ Reinisch W W D'Haens G G Robinson A M AM Wang W W Huang B B Lazar A A Thakkar R B RB Colombel J-F JF

Alimentary pharmacology & therapeutics 20150903 9

<h4>Background</h4>Associations between patient-reported outcomes and mucosal healing have not been established in ulcerative colitis (UC).<h4>Aim</h4>To evaluate relationships of rectal bleeding and stool frequency with mucosal healing and quality of life (QoL) in patients with UC in two Phase 3 studies (ULTRA 1 and 2).<h4>Methods</h4>Associations of patient-reported rectal bleeding and stool frequency subscores with mucosal healing (Mayo endoscopy subscore = 0 or 0/1) and QoL [inflammatory bow ...[more]

PMID: 26381802

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Project description:BackgroundTreatment targets for ulcerative colitis are evolving towards achievement of endoscopic improvement and remission in addition to symptom resolution. It remains to be accurately quantified what proportion of patients with symptom resolution have residual endoscopic activity that might warrant treatment modification.AimTo quantify the prevalence of endoscopic improvement and remission amongst ulcerative colitis patients with various permutations of patient-reported outcomes.MethodsIndividual participant data from active intervention and placebo arms of clinical trials of infliximab, golimumab, vedolizumab and tofacitinib were pooled to estimate the prevalence of endoscopic improvement (Mayo endoscopic sub-score [MES] 0 or 1) and remission (MES 0) scores with various permutations of the rectal bleeding sub-score (RBS) and stool frequency sub-score (SFS) of the Mayo score, following induction (6-8 weeks) and maintenance (30-54 weeks) therapy. Subgroup analyses were performed by year of publication and centrally read endoscopy scoring.ResultsData from 2586 trial participants were analysed. Using locally scored endoscopy, the prevalence of endoscopic improvement and remission was highest among participants with a RBS 0 + SFS 0 post-induction (MES 0/1:81%, [95% CI 78-84]; MES 0:29% [26-33]) and during maintenance (MES 0/1:91% [87-93]; MES 0:57% [52-62]). Prevalence estimates were lower for more recently performed trials (P < .01). In comparison to locally scored endoscopy, when using central endoscopy scoring, the prevalence of endoscopic improvement and remission was lower post-induction (MES 0/1 57% [50-64], P < .001; MES 0 15% [11-21], P = .09) and during maintenance (MES 0/1 74% [67-81], P = .001; MES 0 31% [24-38], P = .001) for participants achieving a RBS 0 + SFS 0.ConclusionsApproximately 8 of 10 patients with normalisation of rectal bleeding and stool frequency have improvement in endoscopic disease activity, whereas approximately only half of these patients have endoscopic remission.

Project description:BackgroundUlcerative colitis (UC) and Crohn's disease (CD) are associated with a range of symptoms that adversely affect health-related quality of life. This research aimed to develop and validate two patient-reported outcome (PRO) tools to assess signs and symptoms in patients with moderate-to-severe UC or CD.MethodsPRO-UC and PRO-CD Diaries were developed in accordance with US Food and Drug Administration (FDA) recommendations. Data were collected from concept elicitation interviews (in which patients described their symptoms and experience of the disease) and further refined through cognitive interviews (in which patients assessed the relevance and clarity of questions in the tools).ResultsInterviews were conducted with 12 patients for each indication. Five symptoms (urgent bowel movements, abdominal pain, frequent bowel movements, bloody stools, diarrhea/watery stools) were reported by 83-100% of participants with UC and were included in the final 6-item PRO-UC Diary: stool frequency, rectal bleeding (2 items), diarrhea, rectal urgency, and abdominal pain. For CD, seven symptoms (abdominal pain, diarrhea/loose stools, urgent bowel movements, fatigue/tiredness/weakness, frequent bowel movements, bloody stools, nausea) were reported by 50-100% of participants. These, together with vomiting and incontinence (reported by 42% and 33% of participants, respectively), were included in the final 10-item PRO-CD Diary, covering abdominal pain (2 items), stool frequency, liquid/very soft stool frequency, rectal bleeding, rectal urgency, nausea, vomiting, bowel incontinence, and general well-being. Symptoms were consistently cited across both indications to have an impact on quality of life, with frequent complaints being the need to always be near a toilet and inability to leave home, as well as general pain, discomfort, and nausea. For both tools, questions were accurately interpreted, with at least 67% of participants in both indications stating that items were easy to answer/relevant to their condition and symptoms were easy to recall over the last 24 h.ConclusionsBoth the PRO-UC and PRO-CD Diaries were developed and validated in accordance with FDA recommendations, providing two new tools for use in clinical trials to assess response to treatment in patients with UC or CD. Psychometric analyses are warranted to fully evaluate their properties and value for use in clinical trials.

Project description:Background & aimsLittle is known about the association between rectal bleeding and increased stool frequency with endoscopic findings in patients with mild to moderate ulcerative colitis (UC). We evaluated the associations between rectal bleeding or stool frequency and endoscopic remission in this population.MethodsWe performed a post-hoc analysis of data from a phase 3 non-inferiority trial of 817 adults with mild to moderate UC who received treatment with mesalazine. We obtained information on rectal bleeding, stool frequency, and Mayo endoscopic subscores (MESs) at weeks 0, 8, and 38. The sensitivity, specificity, and positive and negative predictive values with which rectal bleeding and stool frequency identified patients with MESs of 0 and/or 1 were calculated at weeks 8 and 38 of treatment. The associations between change in rectal bleeding and stool frequency and change in MES after treatment were quantified using the Spearman's rank correlation coefficient.ResultsAmong patients with a MES of 0, 7/82 patients (9%) had a rectal bleeding score of 1 or more and 40/82 patients (49%) had a stool frequency score of 1 or more at week 8; at week 38, 6/167 patients (4%) had a rectal bleeding score of 1 or more and 63/167 patients (38%) had a stool frequency score of 1 or more. Among patients with MESs of 0 or 1, 50/310 patients (16%) had a rectal bleeding score of 1 or more and 162/310 patients (52%) had had a stool frequency score of 1 or more at week 8; at week 38, 18/363 patients (5%) had a rectal bleeding score of 1 or more and 141/363 patients (39%) had a stool frequency score of 1 or more. The Spearman rank correlation coefficients for change in rectal bleeding and stool frequency with change in MES at week 8 were 0.39 (95% CI, 0.32-0.45) and 0.34 (95% CI, 0.27-0.40), respectively. In patients with reduced MESs at week 8, 39/389 patients (10%) had unchanged or worsening rectal bleeding and 81/389 patients (21%) had unchanged or increasing stool frequencies.ConclusionsIn a post-hoc analysis of data from a phase 3 trial of adults with mild to moderate UC treated with mesalazine, we found absence of rectal bleeding to identify patients in endoscopic remission. However, many patients in remission still have increased stool frequency, indicating that it may not be a sensitive marker of disease activity in patients with mild to moderate UC.

Project description:A subset of patients with ulcerative colitis (UC) present with, or progress to, moderate to severe disease activity. These patients are at high risk for colectomy, hospitalization, corticosteroid dependence, and serious infections. The risk of life-threatening complications and emergency colectomy is particularly high among those patients hospitalized with acute severe ulcerative colitis. Optimal management of outpatients or inpatients with moderate to severe UC often requires the use of immunomodulator and/or biologic therapies, including thiopurines, methotrexate, cyclosporine, tacrolimus, TNF-? antagonists, vedolizumab, tofacitnib, or ustekinumab, either as monotherapy or in combination (with immunomodulators), to mitigate these risks. Decisions about optimal drug therapy in moderate to severe UC are complex, with limited guidance on comparative efficacy and safety of different treatments, leading to considerable practice variability. Therefore, the American Gastroenterological Association prioritized development of clinical guidelines on this topic. To inform the clinical guidelines, this technical review was completed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework. Focused questions in adult outpatients with moderate to severe UC included: (1) overall and comparative efficacy of different medications for induction and maintenance of remission in patients with or without prior exposure to TNF-? antagonists, (2) comparative efficacy and safety of biologic monotherapy vs combination therapy with immunomodulators, (3) comparative efficacy of top-down (upfront use of biologics and/or immunomodulator therapy) vs step-up therapy (acceleration to biologic and/or immunomodulator therapy only after failure of 5-aminosalicylates, and (4) role of continuing vs stopping 5-aminosalicylates in patients being treated with immunomodulator and/or biologic therapy for moderate to severe UC. Focused questions in adults hospitalized with acute severe ulcerative colitis included: (5) overall and comparative efficacy of pharmacologic interventions for inpatients refractory to corticosteroids, in reducing risk of colectomy, (6) optimal dosing regimens for intravenous corticosteroids and infliximab in these patients, and (7) role of adjunctive antibiotics in the absence of confirmed infections.

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Randomised clinical study: discrepancies between patient-reported outcomes and endoscopic appearance in moderate to severe ulcerative colitis.

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Randomised clinical study: discrepancies between patient-reported outcomes and endoscopic appearance in moderate to severe ulcerative colitis.

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