Early Use of Biologics Reduces Healthcare Costs in Crohn's Disease: Results from a United States Population-Based Cohort.

BACKGROUND: Early initiation of biologics in moderate-to-severe Crohn's disease (CD) may significantly alter disease progression, resulting in better patient outcomes. Limited real-world data exist on the impact of early biologic use in patients with CD in the United States. AIMS: We aimed to characterize biologic initiation and subsequent healthcare resource utilization (HCRU) in adults with recently diagnosed CD. METHODS: Patients with CD who initiated biologic treatment within 2 years of diagnosis (index date) were identified from medical and pharmacy claims (Merative L.P. MarketScan Database from 2010 to 2016) and classified as early (≤ 12 months post-index) or late (> 12-24 months post-index) biologic initiators. Propensity score matching balanced patient characteristics up to 1 year post-index. Differences in HCRU frequency and costs 1-2 years post-index were compared between the matched groups. RESULTS: After propensity score matching, 672 pairs of early and late biologic initiators were identified. Patients who initiated biologics early had fewer outpatient visits (15.5 vs 19.8, 95% confidence interval [CI] for difference: 2.7, 6.1) and lower total medical costs ($13,646.20 vs $22,180.70, 95% CI for difference: 4748.9, 12,320.1) 1-2 years post-index than late biologic initiators. Early biologic initiators had higher medication costs 1-2 years post-index ($33,766.30 vs $30,580.70, 95% CI: 546.1, 5825.1) but lower combined medical and medication costs ($47,412.50 vs $52,761.50, 95% CI: 801.5, 9896.40). CONCLUSIONS: While biologic treatments are costly, patients initiating biologics sooner after diagnosis appear to have better HCRU outcomes and require fewer healthcare resources at 1-2 years post-index, potentially leading to overall cost savings.

Rectal Urgency Among Patients With Ulcerative Colitis or Crohn's Disease: Analyses from a Global Survey.

Background: Rectal urgency is a common but under-reported inflammatory bowel disease (IBD) symptom. The present study assessed the prevalence of rectal urgency and its association with disease activity and patient-reported outcomes (PROs) among patients with ulcerative colitis (UC) or Crohn's disease (CD) in a real-world setting. Methods: Data were drawn from the 2017-2018 Adelphi IBD Disease Specific Programme™, a multi-center, point-in-time survey of gastroenterologists and consulting adult patients with UC or CD in France, Germany, Italy, Spain, the United Kingdom, and the United States. Gastroenterologists completed patient record forms and patients completed self-reported forms. Analyses were conducted separately for patients with UC or CD. Patient demographics, clinical characteristics, disease activity, symptoms, and PROs were compared between patients with and without rectal urgency. Results: In total, 1057 patients with UC and 1228 patients with CD were included. Rectal urgency was reported in 20.2% of patients with UC and 16.4% with CD. Patients with rectal urgency were more likely to have moderate or severe disease (UC or CD: P < .0001), higher mean Mayo score (UC: P < .0001), higher mean Crohn's Disease Activity Index score (CD: P < .0001), lower Short IBD Questionnaire scores (UC or CD: P < .0001), and higher work impairment (UC: P < .0001; CD: P = .0001) than patients without rectal urgency. Conclusions: Rectal urgency is a common symptom associated with high disease activity, decreased work productivity, and worse quality of life. Further studies are needed to include rectal urgency assessment in routine clinical practice to better gauge disease activity in patients with UC or CD.

Identifying Measures of Suboptimal Healthcare Interaction (SOHI) to Develop a Claims-Based Model for Predicting Patients with Inflammatory Bowel Disease at Risk for SOHI.

BACKGROUND: Understanding the demographic and clinical characteristics of patients with Inflammatory Bowel Disease (IBD) who are likely to experience poor disease outcomes may allow early interventions that can improve health outcomes. OBJECTIVES: To describe demographic and clinical characteristics of patients with ulcerative colitis (UC) and Crohn's disease (CD) with the presence of at least one Suboptimal Healthcare Interaction (SOHI) event, which can inform the development of a model to predict SOHI in members with IBD based on insurance claims, with the goal of offering these patients some additional intervention. METHODS: We identified commercially insured individuals with IBD between 01 January 2019 and 31 December 2019 using Optum Labs' administrative claims database. The primary cohort was stratified on the presence or absence of ≥ 1 SOHI event (a SOHI-defining data point or characteristic at a specific time point) during the baseline observation period. SOHI was deployed as the basis for the development of a model to predict which individuals with IBD were most likely to continue to have SOHI within a 1-year timeframe (follow-up SOHI) using insurance claims data. All baseline characteristics were analyzed descriptively. Multivariable logistic regression was used to examine the association of follow-up SOHI with baseline characteristics. RESULTS: Of 19,824 individuals, 6872 (34.7%) were found to have follow-up SOHI. Individuals with follow-up SOHI were more likely to have had similar SOHI events in the baseline period than those with non-SOHI. A significantly greater proportion of individuals with SOHI had ≥ 1 claims-based C-reactive protein (CRP) test order and ≥ 1 CRP lab results compared with non-SOHI. Individuals with follow-up SOHI were more likely to incur higher healthcare expenditures and resource utilization as compared with non-SOHI individuals. A few of the most important variables used to predict follow-up SOHI included baseline mesalamine use, count of baseline opioid fills, count of baseline oral corticosteroid fills, baseline extraintestinal manifestations of disease, proxy for baseline SOHI, and index IBD provider specialty. CONCLUSION: Individuals with SOHI are likely to have higher expenditures, higher healthcare resource utilization, uncontrolled disease, and higher CRP lab results as compared with non-SOHI members. Distinguishing SOHI and non-SOHI patients in a dataset could efficiently identify potential cases of poor future IBD outcomes.

We have developed a model for identifying suboptimal healthcare interactions (SOHI) at follow-up and used it to predict the individuals with inflammatory bowel disease (IBD) who are likely to suffer poor healthcare outcomes. Our study showed that the SOHI and non-SOHI cohorts had notable differences in clinical baseline characteristics. Compared with non-SOHI members, individuals with SOHI experienced poor IBD outcomes and incurred higher healthcare resource utilization and costs. Understanding baseline characteristics of patients with SOHI to predict follow-up SOHI can improve health outcomes by early identification of patients with IBD who are likely to experience it. This can help in targeting efforts toward additional care, resulting in greater chances of a well-managed disease.

Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn's disease and ulcerative colitis in the United States.

BACKGROUND: The purpose of this analysis was to assess the frequency of inadequate response over 1 year from advanced therapy initiation among patients with Crohn's disease (CD) or ulcerative colitis (UC) in the United States using a claims-based algorithm. Factors associated with inadequate response were also analyzed. METHODS: This study utilized claims data of adult patients from the HealthCore Integrated Research Database (HIRD®) from January 01, 2016 to August 31, 2019. Advanced therapies used in this study were tumor necrosis factor inhibitors (TNFi) and non-TNFi biologics. Inadequate response to an advanced therapy was identified using a claims-based algorithm. The inadequate response criteria included adherence, switching to/added a new treatment, addition of a new conventional synthetic immunomodulator or conventional disease-modifying drugs, increase in dose/frequency of advanced therapy initiation, and use of a new pain medication, or surgery. Factors influencing inadequate responders were assessed using multivariable logistic regression. RESULTS: A total of 2437 patients with CD and 1692 patients with UC were included in this analysis. In patients with CD (mean age: 41 years; female: 53%), 81% had initiated TNFi, and 62% had inadequate response. In patients with UC (mean age: 42 years; female: 48%), 78% had initiated a TNFi, and 63% had an inadequate response. In both patients with CD and UC, inadequate response was associated with low adherence (CD: 41%; UC: 42%). Inadequate responders were more likely to be prescribed a TNFi (for CD: odds ratio [OR] = 1.94; p < 0.001; for UC: OR = 2.76; p < 0.0001). CONCLUSION: More than 60% of patients with CD or UC had an inadequate response to their index advanced therapy within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD and UC appears useful to classify inadequate responders in health plan claims data.

Changes in health-related quality of life and associations with improvements in clinical efficacy: a Phase 2 study of mirikizumab in patients with ulcerative colitis.

OBJECTIVE: Mirikizumab, a monoclonal antibody targeting the interleukin-23 p19 subunit, was effective in a Phase 2 study (NCT02589665) of moderately-to-severely active ulcerative colitis (UC). We studied mirikizumab's impact on health-related quality of life (HRQoL). DESIGN: HRQoL was evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and 36-Item Short Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS). Mixed effects models for repeated measures compared score changes between mirikizumab and placebo groups. Additional analyses evaluated associations between HRQoL score changes and achievement of efficacy endpoints at weeks 12 and 52. RESULTS: At week 12, IBDQ improved compared with placebo for all mirikizumab groups except mirikizumab 50 mg (50 mg, p=0.073; 200 mg, p<0.001; 600 mg, p<0.001). SF-36 PCS was significantly higher in all mirikizumab groups at week 12 (50 mg, p=0.011; 200 mg, p=0.022; 600 mg, p=0.002); MCS was significantly higher in mirikizumab 200 and 600 mg groups compared with placebo (50 mg, p=0.429; 200 mg, p=0.028; 600 mg, p<0.001). Achievement of clinical response and remission were associated with greater HRQoL improvements at week 12. Improvements in HRQoL scores were sustained through week 52. Of the clinical symptoms evaluated, reduction in rectal bleeding was associated with greater improvements in IBDQ and SF-36 scores. CONCLUSION: Mirikizumab improved HRQoL in patients with moderately-to-severely active UC.

Qualitative interviews to evaluate content validity of the ACTIV-2 COVID-19 Symptom Diary (ACSD).

BACKGROUND: Patient-reported outcome measures are needed to assess the impact of treatments for COVID-19 on symptoms. The ACTIV-2 COVID-19 Symptom Diary (ACSD) is being used in the ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines-2 (ACTIV-2) platform clinical trial. The purpose of the current study was to conduct qualitative interviews to assess content validity of the ACSD. METHODS: Interviews were conducted with adults who had tested positive for SARS-CoV-2. The ACSD begins with global items, followed by a symptom checklist. Each interview began with concept elicitation focusing on participant experiences with COVID-19. Then, participants completed the ACSD, and cognitive interviews were conducted to evaluate the questionnaire. Interviews were recorded, transcribed, and coded following a qualitative content analysis. For the qualitative analysis, a coding dictionary was developed with a list of all potential codes and instructions for how the codes should be applied and combined. RESULTS: Interviews were conducted with 30 participants (mean age = 39 years; 57% female; 17% Latinx; 17% Black/African American; 40% meeting at least one criterion for classification as high risk of progression to severe COVID-19). Commonly reported symptoms included fatigue (reported by 100% of the sample), body pain/muscle pain/aches (87%), headaches (87%), cough (83%), loss of smell (73%), shortness of breath/difficulty breathing (70%), and chills (70%). The 13 symptoms most commonly reported in this study are included in the ACSD. After completing the ACSD, participants consistently reported that it was clear and easy to complete, and all items were generally interpreted as intended. Based on participants' input, the ACSD was edited slightly after the first 13 interviews, and the revised version was used for the final 17 interviews. Two additional items assessing "brain fog" and dizziness were recommended for addition to the ACSD in future research. CONCLUSIONS: This qualitative study supports the content validity of the ACSD for assessment of COVID-19 symptoms. Quantitative research with larger samples will be needed to examine the questionnaire's measurement properties.

This study focused on the ACTIV-2 COVID-19 Symptom Diary (ACSD), a questionnaire that assesses symptom severity of COVID-19. The ACSD begins with global items assessing overall symptom severity, followed by a symptom checklist focusing on individual symptoms. Interviews were conducted with 30 adults who had tested positive for COVID-19. The patients reported their experiences with COVID-19, completed the ACSD, and provided their opinions about the ACSD. Based on input from these patients, the ACSD appears to be clear and easy to complete, and it includes the most common and important symptoms of COVID-19. The ACSD was edited for clarity, and "brain fog" and dizziness were recommended additions for future research. This study suggests that the ACSD is a useful questionnaire for assessment of COVID-19 symptoms in clinical studies. Studies like this are important for ensuring that symptoms are measured appropriately and accurately in clinical trials. Future research with larger samples will be needed to further examine the questionnaire.

Burden of Fatigue Among Patients with Ulcerative Colitis and Crohn's Disease: Results from a Global Survey of Patients and Gastroenterologists.

INTRODUCTION: To assess the prevalence of fatigue and its association with disease activity and patient-reported outcomes among patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: Data from a cross-sectional survey conducted with gastroenterologists and their consulting adult patients with UC or CD were analyzed. Data were collected via gastroenterologist-completed patient record forms and patient-self completion forms. Patient demographics, clinical characteristics, disease activity and medication use were reported by the gastroenterologist, while current symptoms (fatigue, rectal urgency, abdominal pain, sleep disturbance), work productivity and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) were reported by the patient. Logistic regression models were used to identify measures associated with fatigue and expressed as odds ratio (OR) with 95% confidence interval. p < 0.05 was considered statistically significant. RESULTS: A total of 1057 patients with UC and 1228 patients with CD were included in this analysis. Fatigue was reported in 22.6% of UC and 26.0% of patients with CD. Higher proportion of patients with UC and fatigue had moderate/severe disease activity (p = 0.0001), had a higher Mayo score (5.0 vs. 4.0, p < 0.0001) and were unemployed (5.6% vs. 3.9%, p = 0.0149) compared to those without fatigue. In patients with CD reporting fatigue, a higher proportion were female (55.9% vs. 48.2%, p = 0.0193), were unemployed (5.8% vs. 4.9%, p = 0.0069), had moderate/severe disease (p < 0.0001) and had a higher mean Crohn's Disease Activity Index score (145.0 vs. 96.2, p < 0.0001) than patients without fatigue. Patients with UC and fatigue had higher mean level of pain (p < 0.0001) and sleep disturbance (p < 0.0001), whereas patients with CD and fatigue had lower SIBDQ scores (p < 0.0001) and greater work impairment (p = 0.0015) than patients without fatigue. Abdominal pain (OR: 2.01, p = 0.001) and use of immunomodulators (OR: 1.69, p = 0.006) increased the odds of having fatigue in patients with UC. In patients with CD, abdominal pain (OR: 2.29, p < 0.001) and use of biologics or biosimilars (OR: 2.02, p = 0.003) increased the odds of having fatigue. CONCLUSION: Fatigue is a common symptom among patients with UC or CD that is associated with higher levels of disease activity and decreased work productivity and is driven by various factors. A multidisciplinary approach may be needed to manage fatigue.

Exploring Disease Remission and Bowel Urgency Severity Among Adults with Moderate to Severe Ulcerative Colitis: A Qualitative Study.

Purpose: Achieving and maintaining symptom control is a key treatment goal in ulcerative colitis (UC). Bowel urgency is an important symptom of UC, thus measurement of urgency is critical. This research explored the patient experience of UC and "remission" in UC, with a focus on urgency, and cognitively debriefed the Urgency Numeric Rating Scale (NRS), including score interpretation and examination of meaningful improvement. Patients and Methods: Semi-structured hybrid concept elicitation and cognitive debriefing interviews with adults with moderately-severely active UC were conducted to explore experiences of UC and urgency, as well as examine meaningful improvement and score interpretation of the Urgency NRS. Purposive sampling was used to identify 20 eligible adult participants with UC. Concept elicitation data were analyzed using thematic analysis, and a deductive approach was used to analyze cognitive debriefing data. Thematic analysis was also applied to meaningful change-related data. Results: Twenty participants were interviewed (average age = 42.6 years old, 50% male); 14 with moderately active (70.0%) and 6 with severely active UC (30.0%). Disease remission was not consistently defined by participants and description varied in terms of definition (absence vs not complete absence of symptoms), duration (months vs days) and key symptoms to consider. Urgency was a prominent symptom for all participants, with 8 (40.0%) identifying it as the most bothersome aspect of UC. No issues were identified with the Urgency NRS. Participants were able to define different levels of urgency severity, describe how they relate to daily life impacts, and score them differently on the Urgency NRS. Participants were also able to reflect urgency improvement on the NRS and discuss how small changes in numeric ratings of urgency can reflect meaningful change in the symptom burden of their UC. Conclusion: The Urgency NRS is a content valid and interpretable measure to assess bowel urgency severity.

Medication use among patients with Crohn's disease or ulcerative colitis before and after the initiation of advanced therapy.

BACKGROUND: Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC. METHODS: This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database (HIRD®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test. RESULTS: Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, P < 0.001 in CD; 91.4% vs. 74.3%, P < 0.001 in UC), opioids (49.4% vs. 41.5%, P = 0.004 in CD; 40.8% vs. 36.5%, P = 0.194 in UC), and NSAIDs (23.1% vs. 15.0%, P < 0.001 in CD; 20.9% vs. 15.8%, P = 0.035 in UC), while the use of neuromodulators significantly increased (29.3% vs. 33.7%, P = 0.007 in CD; 29.5% vs. 35.7%; P = 0.006 in UC). CONCLUSIONS: The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies.

Bamlanivimab and Etesevimab Improve Symptoms and Associated Outcomes in Ambulatory Patients at Increased Risk for Severe Coronavirus Disease 2019: Results From the Placebo-Controlled Double-Blind Phase 3 BLAZE-1 Trial.

Background: In the phase 2/3 BLAZE-1 trial, bamlanivimab and etesevimab together reduced coronavirus disease 2019 (COVID-19)-related hospitalizations and any-cause mortality in ambulatory patients. Herein, we assess the impact of bamlanivimab and etesevimab treatment on the severity and length of symptoms and health outcomes among patients at increased risk for severe COVID-19. Methods: In the phase 3 portion of BLAZE-1 (NCT04427501), symptomatic patients with increased risk for severe COVID-19 were randomized (2:1) to a single infusion of 700 mg bamlanivimab and 1400 mg etesevimab or placebo. Hospitalization events, vital signs, and symptomatology were monitored throughout the trial. Results: Overall, 769 patients were randomized to bamlanivimab and etesevimab together (n = 511) or placebo (n = 258). The time to sustained symptom resolution was significantly shorter among patients who received bamlanivimab and etesevimab compared with placebo (8 vs 10 days; P < .01). The median time to first sustained symptom resolution of body aches and pain, chills, fatigue, feeling feverish, headache, and shortness of breath was significantly different in patients receiving bamlanivimab and etesevimab compared to placebo (P < .05). The proportion of patients who experienced COVID-19-related hospitalization by day 29 was significantly reduced among the bamlanivimab and etesevimab group compared with placebo (0.8% vs 5.4%; P < .01). The mean duration of hospital stay was numerically shorter among patients who received bamlanivimab and etesevimab (7.3 vs 13.5 days; P = .16), with fewer intensive care admissions. Conclusions: Patients receiving bamlanivimab and etesevimab together resolved their symptoms more rapidly than those receiving placebo. Bamlanivimab and etesevimab treatment was associated with reduced rates of hospitalizations and shorter hospital stays. Clinical Trials Registration: NCT04427501.

Incorporating patient experience into drug development for ulcerative colitis: development of the Urgency Numeric Rating Scale, a patient-reported outcome measure to assess bowel urgency in adults.

BACKGROUND: Bowel urgency, the sudden or immediate need to have a bowel movement, is a common, bothersome and disruptive symptom of ulcerative colitis (UC). UC treatment goals include control of urgency; however, it is not consistently assessed in UC clinical trials. The Urgency Numeric Rating Scale (NRS) is a new patient-reported measure to assess severity of bowel urgency in adults with UC developed in accordance with Food and Drug Administration guidelines. METHODS: Qualitative interviews were used to develop Urgency NRS. The scale asks patients to report the immediacy status of their UC symptom over the past 24 h on an 11-point horizontal numeric rating scale [0 (No urgency) to 10 (Worst possible urgency)]. Higher scores indicate worse urgency severity. A 2-week diary study assessed floor and ceiling effects, test-retest reliability (intraclass correlation coefficient (ICC) (2,1) between Week 1 and 2), and construct validity (Spearman correlation using Week 1 scores). Weekly scores were calculated as mean score over each 7-day period. RESULTS: Qualitative interviews with 16 UC patients (mean age 37.9 ± 11.6 years; 50% female; 56% White) confirmed relevance, content, and comprehensiveness. The 2-week diary study included 41 UC patients (mean age 44.2 ± 14.6 years; 51% female; 56% White). No ceiling or floor effects were identified. Test-retest reliability was high (ICC = 0.877). Average Urgency NRS and patient global rating of severity scores were highly correlated, with a moderate correlation between average Urgency NRS and stool frequency, demonstrating construct validity. CONCLUSIONS: Bowel urgency is a distinct symptom of UC. The Urgency NRS is a well-defined, content-valid, and reliable measurement of bowel urgency in adults with UC.

The impact of symptom severity on the humanistic and economic burden of inflammatory bowel disease: a real-world data linkage study.

OBJECTIVE: Few studies have examined the association between inflammatory bowel disease (IBD) severity, and humanistic, and economic burden. We addressed this gap using a unique real-world data source that links self-reported patient data from the US National Health and Wellness Survey (NHWS) to claims data. METHODS: This cross-sectional study linked the 2015-2018 US NHWS data with medical, and pharmacy claims. Patients (≥18 years) who self-reported a physician diagnosis of IBD (ulcerative colitis [UC], or Crohn's disease [CD]) in the NHWS, and had a medical or pharmacy claim indicating a possible diagnosis of IBD were included. Disease symptom severity was defined by a weighted symptom score and main outcomes include health-related quality of life (HRQoL), work productivity (WPAI), healthcare resource use (HRU), and associated costs. RESULTS: Overall, 687 patients with IBD were included, of which 347 were identified with UC and 340 with CD. Validation analysis showed that 94.7% of UC and 88.7% of patients with CD who self-reported diagnosis of CD or UC in NHWS had evidence of diagnosis and/or treatment patterns in claims. Patients with both UC and CD with moderate or severe symptoms had significantly lower HRQoL, increased work productivity loss, greater HRU, and associated costs compared with patients with mild symptoms. CONCLUSIONS: Patients with moderate/severe UC or CD experience substantial humanistic, and economic burden compared with patients with mild UC or CD. These factors should be considered within treatment goals for patients in order to provide holistic care beyond the treatment of objective markers or disease severity and symptoms alone.

Efficacy and Safety of Continued Treatment With Mirikizumab in a Phase 2 Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Mirikizumab is an antibody against the p19 subunit of interleukin 23 that has demonstrated clinical efficacy and was well tolerated following 12 weeks of induction treatment in a phase 2 trial of patients with moderate to severe ulcerative colitis. We present results of the open-label extended induction period in patients who did not initially respond to treatment with mirikizumab. METHODS: This study was a continuation of I6T-MC-AMAC, a double-blind trial, performed at 75 sites in 14 countries, in which patients with moderate to severe ulcerative colitis were randomly assigned to 12 weeks induction therapy with 50 mg, 200 mg, or 600 mg mirikizumab or placebo. Patients without a clinical response (a 9-point decrease in Mayo subscore of ≥2 points and ≥35% from baseline and either a decrease of rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1) at week 12 were offered the opportunity to participate in an open-label, extended induction study for another 12 weeks, in which they received either 600 mg intravenous mirikizumab (n = 20) or, following a protocol amendment, 1000 mg intravenous mirikizumab (n = 64) every 4 weeks. At week 24, patients with a clinical response continued the extension maintenance period and received 200 mg subcutaneous mirikizumab. Endpoints included clinical remission (Mayo subscores of 0 for rectal bleeding, 0 or 1 with a 1-point decrease from baseline), clinical response, endoscopic remission (Mayo endoscopic subscore of 0), or endoscopic improvement (endoscopic subscore of 0 or 1), at study weeks 24 and 52. Data were analysed for patients who received mirikizumab or placebo during the induction phase of the study. RESULTS: Among participants who did not respond to induction mirikizumab, 50.0% of those who received the 12-week extension of 600 mg mirikizumab and 43.8% who received the extension of 1000 mg mirikizumab achieved a clinical response; 15.0% and 9.4% achieved clinical remission, respectively. Endoscopic improvement was achieved by 20.0% of subjects in the 600 mg mirikizumab group and 15.6% subjects in the 1000 mg mirikizumab group. Among initial nonresponders to mirikizumab who had clinical response at study week 24 and continued into maintenance therapy, 65.8% maintained the clinical response, 26.3% achieved clinical remission, and 34.2% had endoscopic improvement at week 52. No new safety concerns were identified. CONCLUSIONS: Extended doses of mirikizumab (600 mg and 1000 mg) for an additional 12 weeks produce a clinical response in up to 50% of patients who did not have a clinical response to 12 weeks of induction doses (50 mg, 200 mg, or 600 mg). Most of the responders to the extended doses maintained clinical response for up to 52 weeks. Clinicaltrials.gov no: NCT02589665.

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease.

BACKGROUND: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). METHODS: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. RESULTS: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4-41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7-54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6-55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3-18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. CONCLUSION: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226.

Disease Burden and Patient-Reported Outcomes Among Ulcerative Colitis Patients According to Therapy at Enrollment Into CorEvitas' Inflammatory Bowel Disease Registry.

Background: To evaluate disease burden and patient-reported outcomes (PROs) of ulcerative colitis (UC) patients at enrollment into CorEvitas' Inflammatory Bowel Disease Registry by therapy class. Methods: Between May 3, 2017 and September 3, 2019, 773 UC registry patients were categorized by therapy class at enrollment: patients on 5-aminosalicylic acids (5-ASAs) only (n = 290), and patients on biologics/Janus kinase inhibitors (JAKi) alone or in combination with 5-ASAs or immunosuppressant therapies (BIO/JAKi) (n = 315). To quantify between group differences, the mean/proportional differences and corresponding 95% CIs were calculated. Results: Among 605 UC patients at enrollment, BIO/JAKi patients were younger (44.1 vs. 50.9 years) more were female (58.0% vs. 49.7%), had lower remission (45.4% vs. 60.0%), had more moderate/severe disease (16.5% vs. 7.1%), experienced less proctitis (10.5% vs. 22.1%), but more pancolitis (54.6% vs. 34.1%), more corticosteroid experience (70.8% vs. 44.5%), previous biologic experience (1 prior: 21.6% vs. 2.4%; 2+ prior: 12.1% vs. 0.3%), and shorter duration of current UC therapy (1.6 vs. 3.5 years) than 5-ASAs patients. BIO/JAKi patients had higher current employment than 5-ASAs patients (70.7% vs. 62.4%) and higher mean Work Productivity and Activity Impairment (WPAI) domains for absenteeism (7.3 vs. 2.8) and activity impairment (22.0 vs. 17.5). Conclusions: Among UC patients in a real-world setting, BIO/JAKi patients had less remission, more moderate-to-severe disease, and worse PROs than 5-ASAs patients. These results suggest that despite increased therapeutic options, patients with UC currently being treated with biologics or JAKi may still experience disease burden and continued unmet needs.

Impact of Bowel Urgency on Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis.

Background: Bowel urgency is commonly experienced by patients with ulcerative colitis (UC) and is associated with reduced health-related quality of life (QoL). Mirikizumab, a humanized monoclonal antibody directed against the p19 subunit of IL-23, significantly reduced bowel urgency in a double-blind, randomized, placebo-controlled Phase 2 clinical trial in patients with moderate-to-severe UC (NCT02589665). Methods: All patients (N = 249) reported symptoms including absence or presence of bowel urgency. Absence of urgency was defined as no urgency for the 3 consecutive days prior to each scheduled visit. Missing urgency data were imputed as present. After 12 weeks of induction treatment, patients who achieved clinical response continued maintenance mirikizumab treatment through Week 52. We assessed the relationship of urgency with QoL, clinical outcomes, and inflammatory biomarkers at Weeks 12 and 52. Results: Patients with absence of urgency demonstrated significantly greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores even after adjusting for rectal bleeding (RB) and stool frequency (SF), significantly higher rates of all clinical outcomes at Weeks 12 and 52, and a greater decrease in inflammatory biomarkers C-reactive protein and fecal calprotectin compared to those with presence of urgency. Absence of urgency at Week 12 was associated with improved IBDQ scores at Week 52, while Week 12 RB or SF status was not. Conclusions: Absence of urgency is strongly associated with improvement in QoL as well as clinical measures of UC disease activity. These findings suggest urgency may be a useful surrogate marker of disease activity and an important treatment target for UC.

Prevalence and Factors Associated With Fecal Urgency Among Patients With Ulcerative Colitis and Crohn's Disease in the Study of a Prospective Adult Research Cohort With Inflammatory Bowel Disease.

Background: In patients with ulcerative colitis (UC) and Crohn's disease (CD), this research examined the following: prevalence of fecal urgency (hereafter urgency), association of urgency with inflammatory bowel disease (IBD) symptoms and fecal calprotectin, and association between well-being and urgency. Methods: In this cross-sectional study from the Study of a Prospective Adult Research Cohort with IBD, urgency was categorized as none, mild, and moderate-severe. We examined the prevalence of urgency, association of urgency with IBD symptoms and fecal calprotectin (in a subset) using multinomial logistic regression, and association of well-being (not feeling well vs generally well) with urgency using logistic regression. Results: Among 576 UC patients, 31.4% reported mild and 28.1% moderate-severe urgency. Among 1330 CD patients, 33.8% reported mild and 31.4% moderate-severe urgency. In UC, moderate-severe urgency was associated with: increased average bowel movements/day [odds ratio (OR) 1.23; 95% confidence interval: 1.09, 1.23], increased stool frequency relative to normal (OR, 9.95; 95% CI: 3.21, 30.87), rectal bleeding (OR, 3.36; 95% CI: 1.79, 6.34), moderate-severe abdominal pain (OR, 17.5; 95% CI: 5.38, 56.89), and calprotectin ≥ 250 µg/g (OR, 4.36; 95% CI: 1.50, 12.66). In CD, moderate-severe urgency was associated with: increased average bowel movements/day (OR, 1.23; 95% CI: 1.14, 1.34), increased stool frequency relative to normal (OR, 7.57; 95% CI: 3.30, 17.34), rectal bleeding (OR, 1.77; 95% CI: 1.13, 2.78), and moderate-severe abdominal pain (OR, 7.52; 95% CI: 4.31, 13.14). Reduced well-being was associated with moderate-severe urgency in both UC (OR, 4.20; 95% CI: 1.69, 20.40) and CD patients (OR, 2.52; 95% CI: 1.51, 4.22). Conclusions: Urgency was common and associated with symptoms and biomarkers suggesting active IBD and reduced well-being.

Full, Partial, and Modified Permutations of the Mayo Score: Characterizing Clinical and Patient-Reported Outcomes in Ulcerative Colitis Patients.

Background: Understanding ulcerative colitis disease activity assessed via the full, modified, or partial Mayo Score may help clinicians apply results from clinical trials to practice and facilitate interpretation of recent and older studies. Methods: Mayo Score variables were assessed in a cross-sectional study of 2608 ulcerative colitis patients. Results: Permutations of Mayo Scores were highly correlated, and models predicting the omitted variable from each permutation demonstrated significant agreement between predicted and observed values. Conclusions: Partial/modified Mayo Scores may be used to predict endoscopic and Physician's Global Assessment scores, and serve as proxies for the full Mayo Score in clinical practice/trials.

Patient's Perspective on Disease Burden, Remission Definition, and Symptoms Associated With Treatment Seeking: A Qualitative Study in Adult and Adolescent Patients With Crohn's Disease.

Background: Disease burden, a definition of remission, and symptoms that drive treatment seeking were explored in a Crohn's disease (CD) population. Methods: A qualitative semistructured interview guide was developed, informed by published literature. Clinicians identified adolescents and adult patients with CD. Face-to-face interviews were audio-recorded and transcribed. Two rounds of interviews were conducted with patients. Transcripts were analyzed using thematic methods facilitated by ATLAS.ti. Results: Twenty-four patients participated in the first round of interviews (n = 16 adults, mean age 50.3 years; n = 8 adolescents, mean age 15.6 years). Abdominal pain (n = 24), urgent bowel movements (n = 24), diarrhea (n = 23), and frequent bowel movements (n = 21) were the most frequently reported symptoms. CD affected patients' physical functioning, daily activities, emotional wellbeing, social functioning, work/education, and relationships. No major difference in disease burden was observed between adolescents and adults. Twenty-three patients (96%) reported they would seek or had sought medical treatment for at least one symptom including abdominal pain (n = 19), diarrhea (n = 12), and blood in stools/rectal bleeding (n = 9). On a 0-10 scale (0 = no symptom and 10 = symptom at its worst possible), most patients (87%, 20/23) answered they would seek/had sought treatment when the symptom's severity was at least 7. In the second round of interviews (n = 6 adults, mean age 51.5 years), 5/6 patients described that they did not require a complete absence of abdominal pain or loose/watery stools to consider their CD to be in remission. Conclusions: CD is associated with substantial disease burden. Worsening of some symptoms drives treatment seeking. To some patients, remission is not defined as a complete absence of symptoms.

Development of the Psoriasis Symptoms Scale (PSS) in patients with moderate-to-severe psoriasis: qualitative and quantitative analyses.

Background: Psoriasis is a chronic inflammatory skin disease.Objective: To establish content validity and assess psychometric properties of the Psoriasis Symptoms Scale (PSS) in patients with moderate-to-severe psoriasis (Ps).Methods: The PSS is an eight-item patient-completed questionnaire assessing symptoms (itch, pain, stinging, burning), signs (redness, scaling, cracking), and discomfort. Content validity was established during interviews of patients (n = 14) with Ps. PSS Symptoms and Signs domain scores were evaluated for reliability, construct validity, and responsiveness using data from a clinical study (NCT02899988) in Ps (n = 205).Results: Patients confirmed content validity; the PSS was understandable and relevant. Cronbach's alphas were 0.84 (Symptoms) and 0.86 (Signs), demonstrating internal consistency reliability. Test-retest reliability was confirmed in patients before receiving study drug (intraclass coefficient: 0.82 [Symptoms]; 0.81 [Signs]). Convergent and discriminant validity were demonstrated at baseline and Week 16 by large (≥0.50) correlations between PSS Symptoms and Signs domain scores and Dermatology Life Quality Index total and symptoms and feelings domain scores, and small (<0.30) correlations with Short Form-36 Mental Component Summary score, respectively. Symptoms and Signs scores responded to clinical changes (p < .001).Conclusions: The PSS Symptoms and Signs domains are valid and reliable assessments of patient-reported symptoms and signs, useful for assessing treatment efficacy.