Association Between Smoking Status and the Efficacy and Safety of Tofacitinib in Patients with Ulcerative Colitis.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This analysis assessed the impact of cigarette smoking on tofacitinib efficacy and safety in the UC clinical program. Methods: Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in the phase (P)2 induction study (baseline demographics and safety only), P3 studies (OCTAVE Induction 1&2, OCTAVE Sustain, OCTAVE Open), and P3/4b RIVETING study. Results: This post hoc analysis included 1156 patients (ever smokers, n = 416 [36.0%; current smokers, n = 59 (5.1%); ex-smokers, n = 357 (30.9%)]; never smokers, n = 740 [64.0%]; median [range] treatment duration 654 [1-2712] and 615.5 [1-2850] days, respectively). Similar proportions of ever smokers and never smokers achieved efficacy endpoints. AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection (serious infections, 5.5%; herpes zoster [nonserious and serious], 10.8%; Clostridioides difficile infection, 12.0%; lower respiratory tract infection, 19.5%: corresponding values among never smokers were 53.1%, 3.9%, 6.8%, 8.5%, and 11.4%). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers and thromboembolism events (venous and arterial) in 1.0% of ever smokers and 0.9% never smokers. Deaths, malignancies (excluding non-melanoma skin cancer [NMSC]), and NMSC occurred infrequently in ever smokers (0.5%, 2.5%, and 3.7%, respectively) and never smokers (0.1%, 1.5%, and 1.0%, respectively). Colorectal cancer was reported in 0.6% of never smokers; no cases occurred in ever smokers. Conclusions: Efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. Overall, serious AEs and, as expected, infections were more frequent in ever smokers versus never smokers. This may inform treatment selection and monitoring strategies. ClinicalTrialsgov: NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304.

The Impact of the COVID-19 Pandemic on Patients with Ulcerative Colitis: Results from a Global Ulcerative Colitis Narrative Patient Survey.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created challenges related to disease management of patients with ulcerative colitis (UC). METHODS: The UC Narrative COVID-19 survey was conducted from August to December 2021 among adults with UC from the United States, Canada, Japan, France, and Finland. Patients were questioned on disease management, health care access and experience, and preferences for interactions with their doctor. Data were analyzed descriptively. RESULTS: In total, 584 patients qualified for and completed the survey. Compared with 2019, 25% experienced more flares during the pandemic (from early 2020). Most patients (88%) taking prescription medication were very/somewhat satisfied with their current treatment plan; 53% were hesitant to make changes during the pandemic. Factors that patients agreed helped control UC symptoms during the pandemic included fewer social outings (37%), working from home (29%), and less busy schedules (28%). Greater anxiety/stress (43%) and hesitancy to visit a hospital/office (34%) made the control of UC symptoms more difficult. Compared with 2019, more patients relied on certain alternative support systems during the pandemic. Patients who used in-person and virtual appointments were equally very satisfied/satisfied with the quality of care (both 81%). In-person appointments were preferred by 68% of patients when meeting a new doctor, 55% when experiencing a flare, and 52% for regular check-ups; 41% preferred virtual appointments for UC prescription refills. CONCLUSION: During the pandemic, most patients were satisfied with their current UC treatment plan and access to care; more patients relied on certain alternative UC management support systems, and many were impacted by anxiety/stress.

The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with ulcerative colitis. These challenges included managing symptoms, lifestyle changes, and access to health care. We asked patients with ulcerative colitis to answer questions about their experience during the pandemic to try to understand how the pandemic was affecting them. A total of 584 patients from the United States, Canada, Japan, France, and Finland took part. Patients were asked questions online. We asked them about their disease activity during the COVID-19 pandemic compared with before the pandemic and how their disease was managed, their access to health care, and their experience during the pandemic. We also asked them about their satisfaction with the types of appointments they had during the pandemic (for example, in-person or virtual meetings), and their interactions and preference for interactions with their doctors. We found that most patients were satisfied with their current treatment plan, their access to health care, and the quality of the care they received. However, many patients experienced greater stress or anxiety, and there was a negative impact on their emotional well-being. During the pandemic, more patients relied on alternative support systems such as online patient portals or virtual appointments, but patients preferred in-person appointments with their doctors in most cases except for refilling prescriptions. This information may help doctors understand the impact of the COVID-19 pandemic on patients with ulcerative colitis, and may help doctors and patients develop treatment plans that include both in-person and virtual appointments.

An Insight into Patients' Perspectives of Ulcerative Colitis Flares via Analysis of Online Public Forum Posts.

BACKGROUND: The knowledge of patients' perceptions of factors contributing to ulcerative colitis (UC) flares is limited; however, online patient communications could offer insight. This analysis aimed to identify the most frequent patient-reported triggers and symptoms of UC flares, which could highlight potential interventions for outcome improvement. METHODS: Online posts written pre- and postflare by patients with UC on 8 public forums in 6 countries between January 1, 2019, and February 14, 2021, were identified using flare-related keywords. Flare-related posts were captured and Netbase Quid™ artificial intelligence text analytics and natural language processing software were used to semantically map and identify commonly discussed themes and topics (subsets of themes). RESULTS: Of >27 000 patient posts, 12 900 were identified as flare related. The most frequent themes were treatment experiences and side effects (28.5% of posts), followed by flare symptoms (22.9% of posts). The most frequent topic was emotional/peer support (9.4% of posts), followed by experiences with mesalamine (and other oral/rectal formulations; 8.0% of posts), and dietary recommendations (6.0% of posts). Stress and anxiety were the most frequently reported flare triggers (37.9% of posts), followed by diet (28.4% of posts). Stress and anxiety were frequently identified as both triggers for, and general symptoms of, flare. Blood in the stool was the most discussed flare indicator (57.8% of posts). CONCLUSIONS: Frequently discussed patient-perceived triggers of UC flares included diet, stress, and anxiety. These results suggest that physicians could incorporate a broader and more holistic approach to UC monitoring and management than is currently practiced.

The patient-reported triggers of flares that were most frequently discussed in online forum posts are not routinely monitored during ulcerative colitis management, emphasizing the need for physicians to incorporate a broader, more holistic approach to ulcerative colitis management than currently practiced.

Health Care Disparities, Social Determinants of Health, and Emotional Impacts in Patients with Ulcerative Colitis: Results from a Global Ulcerative Colitis Narrative Patient Survey.

BACKGROUND: The Ulcerative Colitis (UC) Narrative global survey assessed aspects of living with UC. This analysis aimed to identify health care disparities, social determinants of health, and emotional impacts related to UC disease management, patient experience, and quality of life. METHODS: The survey was conducted by The Harris Poll from August 2017 to February 2018 among adults with UC. Responses from 1000 patients in the United States, Canada, Japan, France, and Finland were analyzed based on patient income, employment status, educational level, age, sex, and psychological comorbidities. Odds ratios (ORs) with significant P values (P < .05) from multivariate logistic regression models are reported. RESULTS: Low-income vs high-income patients were less likely to have participated in a peer mentoring (OR, 0.30) or UC education program (OR, 0.51). Patients not employed were less likely to report being in "good/excellent" health (OR, 0.58) than patients employed full time. Patients with low vs high educational levels were less likely to have reached out to patient associations/organizations (OR, 0.59). Patients aged younger than 50 years vs those aged 50 years and older were less likely to have visited an office within an inflammatory bowel disease center/clinic in the past 12 months (OR, 0.53). Males were less likely to be currently seeing their gastroenterologist than females (OR, 0.66). Patients with vs without depression were less likely to agree that UC had made them more resilient (OR, 0.51). CONCLUSIONS: Substantial differences in disease management and health care experience were identified, based on categories pertaining to patient demographics and psychological comorbidities, which may help health care providers better understand and advance health equity to improve patient care.

Patient-reported survey results revealed substantial differences in disease management and health care experience in patients with ulcerative colitis, based on categories pertaining to patient demographics and diagnosed psychological comorbidities, including income level, employment status, educational level, age, sex, depression, and anxiety.

Health-Related Quality of Life Outcomes With Tofacitinib Treatment in Patients With Ulcerative Colitis in the Open-Label Extension Study, OCTAVE Open.

BACKGROUND: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We report health-related quality of life (HRQoL) outcomes in patients with ulcerative colitis in the phase 3 open-label, long-term extension study, OCTAVE Open. METHODS: The Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQoL-5 Dimensions Health Questionnaire, and 36-Item Short Form Survey scores were analyzed up to month (M) 72 in 4 subpopulations: patients in remission at baseline (maintenance remitters) assigned tofacitinib 5 mg twice daily and patients not in remission at baseline (maintenance nonremitters, maintenance treatment failures, and induction nonresponders [IndNRs]) assigned tofacitinib 10 mg twice daily in OCTAVE Open. Data were analyzed overall and stratified by corticosteroid use at baseline, prior tumor necrosis factor inhibitor failure, and prior immunosuppressant failure. RESULTS: Among maintenance remitters and nonremitters, HRQoL outcomes were maintained up to M72: 80.0% and 100.0% of patients had an IBDQ total score ≥170, respectively. At baseline, 7.4% of maintenance treatment failures had an IBDQ total score ≥170, and this increased to 54.3% and 75.0% at M2 and M72, respectively. Corresponding values for IndNRs were 22.6%, 51.0%, and 86.0%. HRQoL outcomes were independent of treatment history. Among patients not in remission at baseline, improvement in EuroQoL-5 Dimensions Health Questionnaire and 36-Item Short Form Survey scores was maintained or achieved by M2, and steady to M72 or M33, with maintenance treatment failures and IndNR subpopulations undergoing the biggest improvements from baseline. CONCLUSIONS: A continued favorable impact on HRQoL was revealed with long-term tofacitinib treatment in OCTAVE Open, regardless of baseline remission status or treatment history. (ClinicalTrials.gov; number: NCT01470612).

Health-related quality of life was assessed in patients with ulcerative colitis in an open-label, long-term extension study, OCTAVE Open. Patients had sustained beneficial effects on health-related quality of life with long-term tofacitinib treatment, regardless of treatment history/remission status at OCTAVE Open baseline.

Disease Activity and Health-related Quality of Life Relationships with Work Productivity in Patients with Ulcerative Colitis in OCTAVE Induction 1 and 2 and OCTAVE Sustain.

BACKGROUND: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis [UC]. We evaluated the relationship between Mayo/Inflammatory Bowel Disease Questionnaire [IBDQ] scores and Work Productivity and Activity Impairment-UC [WPAI-UC] components in patients with UC. METHODS: All available pooled data from three Phase 3 tofacitinib studies [OCTAVE Induction 1 and 2 and OCTAVE Sustain] were included. Relationships were estimated using repeated measures regression models with Mayo score/subscores or IBDQ total/domain scores as a separate anchor predictor and WPAI-UC components as the outcome. RESULTS: Evidence for linear relationships was confirmed between Mayo/IBDQ scores and WPAI-UC components. Robust relationships between total Mayo score/IBDQ total score and WPAI-UC presenteeism, work productivity loss, and activity impairment were observed; relationships with absenteeism were weak. Total Mayo scores of 0 and 12 corresponded, on average, to WPAI-UC component scores of < 15% and ≥ 60%, respectively, and IBDQ total scores of 224 and 32 corresponded, on average, to WPAI-UC component scores of < 6% and ≥ 90%, respectively. Presenteeism, work productivity loss, and activity impairment [all 0-100%], respectively, improved on average by 14.7, 13.6, and 16.4 percentage points for every 3-point improvement in total Mayo score, and by 8.1, 7.9, and 8.8 percentage points for every 16-point improvement in IBDQ total score. CONCLUSION: Robust relationships between Mayo/IBDQ scores with WPAI-UC presenteeism, work productivity loss, and activity impairment suggest that patient productivity and non-work activities are strongly associated with disease activity and HRQoL. The weak relationships with absenteeism suggest that patients attend work regardless of their disease activity/poor HRQoL. ClinicalTrials.gov: NCT01465763;NCT01458951;NCT01458574.

Notable gaps between patients' and physicians' perspectives on communication and disease management in Japan: multifaceted ad hoc analyses of the global Ulcerative Colitis Narrative Survey for further optimal care.

Introduction: The patient-physician relationship is important in implementing appropriate management strategies. The Ulcerative Colitis (UC) Narrative Global Surveys examined patient and physician views on multiple aspects of living with UC. However, there are many other important undiscovered aspects of UC to consider for patients in Japan. Aim: The aim of these ad hoc analyses was to identify detailed practical issues for further optimal care. Methods: Patient and physician questionnaires covered broad aspects of living with UC and practical care. Results were compared to identify gaps. We conducted multifaceted ad hoc analyses on the responses from Japan. Results: In Japan, 210 patients with UC and 151 physicians were surveyed. Most (64%) patients felt they would be more successful if they did not have UC. Physicians were more likely to discuss treatment-related topics, including side effects as a proxy for medication satisfaction, than quality of life-related topics. Physicians underestimated the importance to patients of toileting accidents (28% vs 54%) and overestimated the importance of mucosal healing (59% vs 29%). Although 72% of patients felt comfortable raising concerns with their physician, 53% worried about asking too many questions, as they thought they would be seen as a difficult patient, and 66% wished they had talked more about medication fears. The majority (83%) of patients said they were honest with their physician when discussing their experiences with UC, although 45% regretted not telling them more. Some (26%) patients believed, and some (20%) were not sure, that if their symptoms were under control then their UC was not active. More positively, 65% of patients agreed that UC had made them more appreciative of the important things in life. Conclusion: This survey revealed notable gaps between patients' and physicians' perspectives. Consequently, the importance of patient-physician communication remains constant, even in the era of biologics and treat-to-target strategies. Plain Language Summary: Overlap and differences in views around communication and management of ulcerative colitis between patients and doctors It is important to discover the different ways that ulcerative colitis (UC) can impact individual patients, and to identify differences in views between people with UC and the doctors treating them, to improve patient care. The UC Narrative is a global survey (containing two questionnaires, one for patients, and one for doctors) that gathers information on how UC impacts patients. The survey aims to identify differences between patients' and doctors' views on communication and disease management.In this analysis, we report the results from 210 patients with UC and 151 doctors who completed the UC Narrative survey in Japan, between November 2017 and January 2018. Most patients (85%) were satisfied with their communication with their doctor. However, doctors underestimated patient satisfaction, as they believed that about 71% of their patients were satisfied with communication. Around two-thirds of patients (65%), and most doctors (82%), wanted more discussion about goals for managing or treating UC. Most patients (83%) said they were honest with their doctor when discussing their experiences with UC, although almost half of patients (45%) said they regretted not telling their doctor more. Three-quarters of doctors (75%) felt that their patients were honest with them. Doctors underestimated the importance of toileting accidents to patients and thought that healing the patients' intestine would be more important to the patients than toileting accidents. Some patients had misconceptions about treatment. For example, only 69% of patients knew that it was not OK to stop taking their UC medications once they felt better. This survey shows that even though treatment options for UC have developed, sufficient communication between patients and doctors is very important for overall patient care.

Validation of a claims-based algorithm to identify cases of ulcerative colitis in Japan.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) is increasing in Japan. Validated claims-based definitions are required to investigate the epidemiology of UC and its treatment and disease course in clinical practice. This study aimed to develop a claims-based algorithm for UC in Japan. METHODS: A committee of epidemiologists, gastroenterologists, and internal medicine physicians developed a claims-based definition for UC, based on diagnostic codes and claims for UC treatments, procedures (cytapheresis), or surgery (postoperative claims). Claims data and medical records for a random sample of 200 cases per site at two large tertiary care academic centers in Japan were used to calculate the positive predictive value (PPV) of the algorithm for three gold standards of diagnosis, defined as physician diagnosis in the medical records, adjudicated cases, or registration in the Japanese Intractable Disease Registry (IDR). RESULTS: Overall, 1139 claims-defined UC cases were identified. Among 393 randomly sampled cases (mean age 44; 48% female), 94% had received ≥ 1 systemic treatment (immunosuppressants, tumor necrosis factor inhibitors, corticosteroids, or antidiarrheals), 7% had cytapheresis, and 7% had postoperative claims. When physician diagnosis was used as a gold standard, PPV was 90.6% (95% confidence interval [CI]: 87.7-93.5). PPV with expert adjudication was also 90.6% (95% CI: 87.7-93.5). PPVs with enrollment in the IDR as gold standard were lower at 41.5% (95% CI: 36.6-46.3) due to incomplete case registration. CONCLUSIONS: The claims-based algorithm developed for use in Japan is likely to identify UC cases with high PPV for clinical studies using administrative claims databases.

Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial.

BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomised, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy. METHODS: Patients had received tofacitinib 10 mg BID for ≥ 2 consecutive years and been in stable remission for ≥ 6 months before enrolment. The primary endpoint was modified Mayo score remission at Month 6. Safety was assessed up to February 20, 2020 [data cut-off]. RESULTS: In all, 140 patients were randomised [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at Month 6 (adjusted difference 12.9%; 95% confidence interval [CI] 0.5-25.0). Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; -3.0-22.6, and 21.1%; -6.1-48.2, respectively], and in patients without versus with prior tumour necrosis factor inhibitor [TNFi] failure [9.5%; -6.6-25.6, and 17.4%; -1.6-36.3, respectively]. Adverse events [AE] and serious AE rates were similar across treatment groups; no deaths were reported. CONCLUSIONS: Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6 months; a longer duration of follow-up during RIVETING will further characterise the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.

Living with Ulcerative Colitis in Japan: Biologic Persistence and Health-Care Resource Use.

OBJECTIVE: The aim of the study was to improve understanding of adherence and persistence to biologics, and their association with health-care resource utilization (HCRU), in Japanese patients with moderate to severe ulcerative colitis (UC). METHODS: Data were from Medical Data Vision, a secondary care administrative database. A retrospective, longitudinal cohort analysis was conducted of data from UC patients initiating biologic therapy between August 2013 and July 2016. Data collected for 2 years prior (baseline) and 2 years after (follow-up) the index date were evaluated. Patients completing biologic induction were identified, and adherence/persistence to biologic therapy calculated. HCRU, steroid, and immunosuppressant use during baseline and follow-up were assessed. Biologic switching during the follow-up was evaluated. Descriptive statistics (e.g., means and proportions) were obtained and inferential analyses (from Student's t tests, Fisher's exact tests, χ2 tests, the Cox proportional hazard model, and negative binomial regression) were performed. RESULTS: The analysis included 649 patients (adalimumab: 265; infliximab: 384). Biologic induction was completed by 80% of patients. Adherence to adalimumab was higher than that to infliximab (p < 0.001). Persistence at 6, 12, 18, and 24 months was higher with infliximab than with adalimumab (p < 0.05). Overall, gastroenterology outpatient visits increased, and hospitalization frequency and duration decreased, from baseline to follow-up. UC-related hospitalizations were fewer and shorter, and endoscopies fewer, in persistent than in nonpersistent patients, although persistent patients made more outpatient visits than nonpersistent patients. Hospitalization duration was lower in persistent than nonpersistent patients. Approximately 50% of patients received an immunosuppressant during biologic therapy; 5% received a concomitant steroid during biologic therapy. Overall, 17% and 3% of patients, respectively, received 2nd line and 3rd line biologics. CONCLUSIONS: Poor biologic persistence was associated with increased non-medication-associated HCRU. Effective treatments with high persistence levels and limited associated HCRU are needed in UC.

Development and evaluation of the diffusive gradients in thin films technique for measuring nitrate in freshwaters.

A new diffusive gradients in thin films (DGT) technique, using Purolite A520E anion exchange resin, was developed and evaluated for the measurement of NO3N in freshwaters. Purolite A520E had a very high uptake efficiency (>98%) and elution efficiency (82.7% with 2 mol L(-1) NaCl as eluent) for NO3N. The 24 h mass vs. time validation experiments had excellent linearity (R(2) ≥ 0.997) and the intrinsic capacity of the binding layer for NO3N was 849 ± 24 µg. NO3N uptake was quantitative over a pH (3.5-8.5) range typical of most natural freshwaters. Several anions competed with NO3N to produce a lower effective binding capacity for NO3N in the following order of selectivity, Cl(-) > HCO3(-) > SO4(2-) > H2PO4(-), although NO3N measurements were quantitative at ionic strengths 0.0001-0.008 mol L(-1) as NaCl. NO2N did not adversely affect determination of NO3N at typical concentrations. Field deployments of DGT samplers with varying diffusive layer thicknesses validated the use of the technique in situ, allowed calculation of the diffusive boundary layer and accurate measurement of NO3N (CDGT/CSOLN 1.03-1.04). Reproducibility of the technique during field deployments was good (relative standard deviation < 3.2%). Limits of detection of A520E-DGT for NO3N were 13.15 µg L(-1) and 7.52 µg L(-1) (equivalent to 0.94 and 0.54 µmol L(-1)) based on 24 h and 48 h deployments, respectively. A520E-DGT determined NO3N concentrations during field deployments were very similar to the average values obtained from 0.45 µm filtered grab samples, which confirmed that the new DGT technique produced highly representative results.

The Effectiveness of Corticosteroid Injection for De Quervain's Stenosing Tenosynovitis (DQST): A Systematic Review and Meta-Analysis.

De Quervain's stenosing tenosynovitis (DQST) treatments include corticosteroid injection around the tendon sheath; however there is some ambiguity concerning the efficacy of this treatment. The aim of this systematic review and meta-analysis is to examine the totality of evidence relating to the use of corticosteroid injection in DQST when compared to placebo or other active treatments. A systematic literature search was conducted in July 2014. Only randomized control trials (RCTs) were included. Outcome measures included impairment, activity limitation and participation restriction. Five RCTs were identified with 165 patients, 88 in the treatment group and 77 in the control group.Patients who received corticosteroid injection (n=142) had a higher rate of resolution of symptoms [RR 2.59, 95% CI: 1.25 to 5.37, p=0.05, I2=62%]. This group reported greater pain relief as assessed by Visual Analogue Scale (VAS) at first assessment [mean difference -2.51, 95% CI: -3.11 to -1.90, p=0.0003, I2=65%] and demonstrated a statistically significant improvement in function (n=78) as measured by the DASH score and Dutch AIMS-HFF score [SMD -0.83, 95% CI: -1.54 to -0.12, p=0.02, I2=48]. This review confirms that corticosteroid injection results in a statistically significant increase in resolution of symptoms, pain relief and increased function in the treatment of DQST.