Residual Disease Burden Among European Patients With Inflammatory Bowel Disease: A Real-World Survey.

BACKGROUND: Understanding disease burden is imperative for improving inflammatory bowel disease (IBD) management. This real-world survey investigated residual disease burden and treatment satisfaction among European patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The Adelphi Real World IBD Disease Specific Programme was a multinational, cross-sectional survey with retrospective collection of patient- and physician-reported data on disease burden and management. Between October 2020 and March 2021, participating gastroenterologists recruited their next 7 (UC) and 8 (CD) eligible patients and reported demographics and clinical characteristics. Patients completed symptom, health-related quality of life (HRQoL), and treatment satisfaction questionnaires. Data were adjusted for confounding variables and compared between patients in remission (clinical remission, endoscopic remission, or both) and not in remission. RESULTS: Overall, 1040 patients (UC, n = 502; CD, n = 538) were included. Although most patients were in remission (UC, 66.1%; CD, 69.5%), most still reported symptoms (UC, 63.7%; CD, 74.1%), including flatulence, fatigue/tiredness, and abdominal pain/distension. In UC, there were no significant differences in the likelihood of experiencing 7 of 23 symptoms between patients in remission and not in remission. In CD, there was no significant difference in 19 of 23 symptoms between patients in remission and not in remission. Several symptoms were significantly associated with reduced HRQoL. HRQoL was significantly better among patients in remission than not in remission. CONCLUSIONS: Patients with IBD, both in remission and not in remission, experience residual symptoms that impair HRQoL. Comprehensive endpoints, incorporating HRQoL and patients' perspectives, and improved treatments are needed to address residual disease and patients' needs.

This real-world study investigated the residual burden of inflammatory bowel disease on European patients. We found that patients­including those in remission­experience significant symptomatic burden and impaired quality of life, highlighting gaps in current therapeutics and patients' unmet needs.

Rates of clinical remission and inadequate response to advanced therapies among patients with ulcerative colitis in Germany.

PURPOSE: Many patients treated for ulcerative colitis (UC) do not achieve clinical remission. This real-world study assessed clinical remission and inadequate response rates among patients with UC in Germany treated with advanced therapies. METHODS: This retrospective chart review included patients with UC newly initiating advanced (index) therapy (anti-TNFα agents, vedolizumab, tofacitinib) from January 2017-September 2019 (index date). Included patients had data for ≥ 12 months before (baseline period) and after the index date (follow-up period). Remission was defined as a partial Mayo score ≤ 1. Indicators of inadequate response were: index therapy discontinuation; therapy adjustments (index therapy dose escalation; augmentation with non-advanced therapies; corticosteroid [CS] use during maintenance therapy); CS dependency (use for ≥ 12 weeks); and UC-related hospitalisation, surgery or emergency department visit. Time to first remission and inadequate response were analyzed using Kaplan-Meier analyses. RESULTS: Among 149 patients with UC (median age: 40 years), 96 (64.4%) were biologic-naïve and 42 (28.2%) received CS at the index date. Within 12 months, 52 patients (47.2%) were in remission; of these, 13 patients (25.0%) received ≥ 1 therapy adjustment. At 12 months, 55 patients (37.6%) had ≥ 1 indicator of an inadequate response. Median time to remission was longer among biologic-experienced vs biologic-naïve patients (24 vs 7 months; p = 0.012). CONCLUSION: Over half of the patients were not in clinical remission after 12 months and more than one-third experienced inadequate response. One-quarter of patients in remission required therapy adjustments. Patients with UC require therapies that are more effective than those currently available to achieve better treatment outcomes.

The incidence of remission and indicators of inadequate response to advanced therapy in patients with ulcerative colitis: results from medical charts in the United Kingdom.

OBJECTIVE: A considerable proportion of patients with moderate-to-severe ulcerative colitis (UC) treated with advanced therapies do not achieve remission, even after 1 year of treatment, and suboptimal response to advanced therapies is frequently observed in clinical practice. This study aimed to analyze clinical practice data in the United Kingdom (UK) and assess the rates of clinical remission and inadequate response with advanced therapies among patients with UC. METHODS: This retrospective chart review included patients with UC who initiated a new advanced therapy (i.e. adalimumab, infliximab, golimumab, tofacitinib, or vedolizumab) between January 2017 and September 2019 from eight clinics across the UK. At least 12 months of data before and after starting an advanced therapy were required. Remission was assessed using components of the Mayo score. Inadequate response was defined by therapeutic adjustment or emergency treatment. RESULTS: Among 238 patients included (female: 46.6%; median age: 42.0 years; median follow-up: 28.8 months), 178 patients (74.8%) were biologic-naïve. At 12 months, 87 patients (53.9%) had achieved remission (median time to remission: 7.6 months), although 29 (33.3%) among them had required therapeutic modifications to achieve remission. At 12 months, 105 patients (44.3%) had at least one indicator of an inadequate response (median time to the first indicator of inadequate response: 18.0 months). CONCLUSIONS: Nearly half of the patients did not achieve remission, and almost half of the included patients had an inadequate response within 1 year after treatment initiation. More effective therapies are needed to effectively treat UC.

Treatment of ulcerative colitis (UC) follows a stepwise approach that considers disease severity and disease activity. It has the goal of achieving and maintaining steroid-free remission and healing of the gut lining. Treatment options for UC include several conventional and advanced therapies. However, suboptimal response to treatment has been reported in previous observational studies. This results in treatment adjustments, such as therapy discontinuation, dose intensification, and addition of conventional therapies, as well as lengthy concurrent use of corticosteroids.This retrospective chart review evaluated clinical practice data from eight clinics across the United Kingdom. This was done to assess rates of clinical remission and indicators of suboptimal response to advanced therapies among patients with UC. The analysis included data from January 2017 to September 2019.Nearly half of the patients did not have clinical remission within 1 year after starting advanced therapies. Optimization of advanced therapies was often seen, even in patients in remission. The most common indicators of suboptimal therapy were therapy discontinuation, dose escalation of advanced therapy, and the addition of conventional therapies. Our findings suggest that the efficacy of advanced therapies to treat UC remains insufficient in clinical practice. Thus, there is a need for more effective treatment alternatives to achieve better outcomes for patients with UC.

Filgotinib Improved Health-Related Quality of Life and Led to Comprehensive Disease Control in Individuals with Ulcerative Colitis: Data from the SELECTION Trial.

BACKGROUND AND AIMS: Ulcerative colitis [UC] impacts patients' health-related quality of life [HRQoL]. We assessed HRQoL and an exploratory patient-level composite endpoint ('Comprehensive Disease Control' [CDC]) in individuals receiving filgotinib [an oral JAK1 preferential inhibitor] in the SELECTION trial. METHODS: In SELECTION [NCT02914522], a double-blind, randomized, placebo-controlled, phase 2b/3 trial, adults with moderately to severely active UC received once-daily filgotinib 200 mg, filgotinib 100 mg or placebo for 11 weeks in Induction Study A [biologic-naïve] or B [biologic-experienced]. Filgotinib responders [week 10 clinical remission/response] were re-randomized to their filgotinib regimen or placebo for the 48-week Maintenance Study. We assessed week 10 and week 58 SF-36, EQ-5D, WPAI and IBDQ scores. Achievement of CDC (patient-level partial Mayo Clinic Score [pMCS] remission [pMCS ≤2, no individual rectal bleeding, stool frequency or physician's global assessment subscore >1], endoscopic improvement [endoscopic subscore ≤1], faecal calprotectin <150 µg/g and IBDQ score ≥170) and its association with HRQoL and histological outcomes were also explored. RESULTS: Analyses included 382 biologic-naïve and 404 biologic-experienced patients. Filgotinib 200 mg induced and maintained improvements vs placebo in SF-36, EQ-5D, WPAI and IBDQ scores, and restored HRQoL by week 10. Proportionally more filgotinib 200 mg- than placebo-treated patients achieved CDC at weeks 10 and 58 [p < 0.01]. CDC was associated with clinically important improvements in HRQoL and histological remission over both periods. CONCLUSIONS: Filgotinib 200 mg results in short- and long-term improvements in HRQoL. High-level improvement of HRQoL relates to a stringent composite endpoint suggesting meaningful disease control in a subset of filgotinib-treated individuals.ClinicalTrials.gov identifier: NCT02914522.

Epidemiology, healthcare utilization, and related costs among patients with IPF: results from a German claims database analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive form of fibrosing interstitial pneumonia with poor survival. This study provides insight into the epidemiology, cost, and disease course of IPF in Germany. METHODS: A cohort of incident patients with IPF (n = 1737) was identified from German claims data (2014-2019). Incidence and prevalence rates were calculated and adjusted for age differences compared with the overall German population. All-cause and IPF-related healthcare resource utilization as well as associated costs were evaluated per observed person-year (PY) following the initial IPF diagnosis. Finally, Kaplan-Meier analyses were performed to assess time from initial diagnosis to disease deterioration (using three proxy measures: non-elective hospitalization, IPF-related hospitalization, long-term oxygen therapy [LTOT]); antifibrotic therapy initiation; and all-cause death. RESULTS: The cumulative incidence of IPF was estimated at 10.7 per 100,000 individuals in 2016, 10.9 in 2017, 10.5 in 2018, and 9.6 in 2019. The point prevalence rates per 100,000 individuals for the respective years were 21.7, 23.5, 24.1, and 24.1. On average, ≥ 14 physician visits and nearly two hospitalizations per PY were observed after the initial IPF diagnosis. Of total all-cause direct costs (€15,721/PY), 55.7% (€8754/PY) were due to hospitalizations and 29.1% (€4572/PY) were due to medication. Medication accounted for 49.4% (€1470/PY) and hospitalizations for 34.8% (€1034/PY) of total IPF-related direct costs (€2973/PY). Within 2 years of the initial IPF diagnosis (23.6 months), 25% of patients died. Within 5 years of diagnosis, 53.1% of patients had initiated LTOT; only 11.6% were treated with antifibrotic agents. The median time from the initial diagnosis to the first non-elective hospitalization was 5.5 months. CONCLUSION: The incidence and prevalence of IPF in Germany are at the higher end of the range reported in the literature. The main driver for all-cause cost was hospitalization. IPF-related costs were mainly driven by medication, with antifibrotic agents accounting for around one-third of the total medication costs even if not frequently prescribed. Most patients with IPF do not receive pharmacological treatment, highlighting the existing unmet medical need for effective and well-tolerated therapies.

Inadequate Response, Treatment Patterns, Health Care Utilization, and Associated Costs in Patients With Ulcerative Colitis: Retrospective Cohort Study Based on German Claims Data.

BACKGROUND: Real-world data regarding response rates in ulcerative colitis treatment are rare, particularly for later lines of therapy. This study aimed to assess continuity of and changes to advanced therapies, as well as costs and specific indicators defining suboptimal therapy. METHODS: German claims data were retrospectively analyzed (January 2014 to June 2019). Patients with ulcerative colitis initiating an advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) were included. Inadequate response was indicated by therapy discontinuation, switch, escalation, augmentation, corticosteroid dependency, disease-related hospitalization, or surgery. Health care resource utilization (inpatient, outpatient, sick leaves, medication, aids, and remedies) and related costs were assessed from therapy initiation until discontinuation or loss to follow-up. RESULTS: Among 574 patients (median age, 39 years; female sex, 53.5%) who initiated advanced therapies, 458 (79.8%) received an antitumor necrosis factor therapy, 113 (19.7%) vedolizumab, and 3 (0.5%) tofacitinib. After 12 months, 75% had ≥1 indicator for suboptimal therapy. The median time to first indicated inadequate response was 4.8 months. Therapy discontinuation (38%), switching (26%), and prolonged use of steroids (36%) were common within the first year of treatment. In an unadjusted comparison, all-cause total costs per person-year were significantly higher in those who switched vs patients remaining on their therapy (€44,570 vs €36,807; P < .001). CONCLUSIONS: Our study indicates a high prevalence of inadequate response to advanced therapies. Only 25% of patients showed adequate response within 12 months after therapy initiation. Frequent dose and treatment changes were observed. The economic impact of suboptimal therapy in ulcerative colitis is substantial, highlighting the ongoing need for improved treatment strategies.

Validation of a derived version of the IPF-specific Saint George's Respiratory Questionnaire.

BACKGROUND: Health-related quality of life (HRQL) is impaired in patients with idiopathic pulmonary fibrosis (IPF). HRQL is often measured using the St. George's Respiratory Questionnaire (SGRQ) despite the development of an IPF-specific version (SGRQ-I). Using data from a real-world cohort of patients with IPF, we aimed to transform SGRQ into a derived version of SGRQ-I, SGRQ-Ider, to examine the cross-sectional and longitudinal validity of SGRQ-Ider and to compare SGRQ-Ider to SGRQ-I. METHODS: Based on results from SGRQ, SGRQ-Ider was derived applying the algorithm used to develop SGRQ-I. Of the 50 items in SGRQ, 34 items were retained in SGRQ-Ider. Response options for seven items were collapsed and minor adjustments were made to the weights of two items after correspondence with the developers of SGRQ-I. Cross-sectional validation, responsiveness and minimal clinically important difference (MCID) were assessed by comparison to other HRQL instruments, pulmonary function tests and 6-min walk test performed at baseline, 6 and 12 months. Furthermore, the association between SGRQ-Ider scores and mortality was examined. RESULTS: A total of 150 IPF patients participated and 124 completed follow-up at 12 months. SGRQ-Ider performed comparably to SGRQ-I with a high concurrent validity, good test-retest reliability and high known-groups validity. SGRQ-Ider was responsive to change in HRQL and physiological anchors. MCID of SGRQ-Ider for improvement and deterioration was 3.5 and 5.7, respectively. SGRQ-Ider scores were associated with mortality in both univariate (HR 1.82, 95% CI 1.42-2.34 per 20-point increase) and multivariate analyses (HR 1.57, 95% CI 1.20-2.05 per 20-point increase). CONCLUSIONS: The SGRQ-Ider is a valid, reliable and responsive HRQL instrument in patients with IPF and has psychometric properties comparable to SGRQ-I. Thus, SGRQ results can reliably be transformed into the SGRQ-Ider. The MCID estimates were calculated for improvement and deterioration separately. Increasing SGRQ-Ider score was associated with increased mortality.

Global incidence and prevalence of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive debilitating lung disease with considerable morbidity. Heterogeneity in epidemiologic studies means the full impact of the disease is unclear. METHODS: A targeted literature search for population-based, observational studies reporting incidence and/or prevalence of IPF from January 2009 to April 2020 was conducted. Identified studies were aggregated by country. For countries with multiple publications, a weighted average was determined. Incidence and prevalence data were adjusted for between-study differences where possible. The final model included adjusted estimates of incidence and prevalence per 10,000 of the population with 95% confidence intervals. As prevalence estimates vary depending on the definitions used, estimates were based on a specific case definition of IPF. RESULTS: Overall, 22 studies covering 12 countries met the inclusion criteria, with 15 reporting incidence and 18 reporting prevalence estimates. The adjusted incidence estimates (per 10,000 of the population) ranged from 0.35 to 1.30 in Asia-Pacific countries, 0.09 to 0.49 in Europe, and 0.75 to 0.93 in North America. Unadjusted and adjusted incidence estimates were consistent. The adjusted prevalence estimates ranged from 0.57 to 4.51 in Asia-Pacific countries, 0.33 to 2.51 in Europe, and 2.40 to 2.98 in North America. South Korea had the highest incidence and prevalence estimates. When prevalence estimates were compared to country-specific rare disease thresholds, IPF met the definition of a rare disease in all countries except South Korea. There were notable geographic gaps for IPF epidemiologic data. CONCLUSIONS: Due to differences in study methodologies, there is worldwide variability in the reported incidence and prevalence of IPF. Based on the countries included in our analysis, we estimated the adjusted incidence and prevalence of IPF to be in the range of 0.09-1.30 and 0.33-4.51 per 10,000 persons, respectively. According to these prevalence estimates, IPF remains a rare disease. For consistency, future epidemiologic studies of IPF should take age, sex, smoking status, and the specificity of case definitions into consideration.

Integrating efficacy and safety of vedolizumab compared with other advanced therapies to assess net clinical benefit of ulcerative colitis treatments: a network meta-analysis.

Objectives: Because only one head-to-head randomized trial of biologics for moderate-to-severe UC has been performed, indirect treatment comparisons remain important. This systematic review and network meta-analysis examined efficacy and safety of biologics and tofacitinib for moderate-to-severe UC, using vedolizumab as reference.Methods: Relevant studies (N = 19) of vedolizumab, adalimumab, infliximab, golimumab, ustekinumab, and tofacitinib were identified. Study design differences were addressed by assessing efficacy outcomes conditional on response at maintenance initiation. Primary analysis used fixed-effect models to estimate odds ratios for efficacy and safety endpoints.Results: Compared with vedolizumab 300 mg, adalimumab 160/80 mg was associated with less clinical remission (odds ratio, 0.69 [95% credible interval, 0.54-0.88]), and infliximab 5 mg/kg was associated with more clinical remission (1.67 [1.16-2.42]) and response (1.63 [1.15-2.30]). Adalimumab 40 mg, golimumab 50 mg, and ustekinumab 90 mg Q12W had significantly lower clinical remission rates during maintenance (0.62 [0.45-0.86], 0.55 [0.32-0.95], and 0.59 [0.35-0.99]) versus vedolizumab 300 mg Q8W. Response results were similar. Tofacitinib 10 mg had the highest maintenance treatment efficacy estimates and highest infection risk.Conclusion: Network meta-analysis and novel integrated benefit-risk analysis suggest a potentially favorable efficacy-safety balance for vedolizumab vs adalimumab and other advanced UC therapies.

Efficacy of biologic therapies for biologic-naïve Japanese patients with moderately to severely active ulcerative colitis: a network meta-analysis.

BACKGROUND/AIMS: Several biologic therapies are approved in Japan to treat moderately to severely active ulcerative colitis (UC), but there are no published comparative efficacy studies in a Japanese population. We compared the efficacy of biologics approved in Japan (adalimumab, infliximab, golimumab, and vedolizumab) for treating biologic-naïve patients with UC at their approved doses. METHODS: A targeted literature review identified 4 randomized controlled trials of biologics for UC in biologicnaïve Japanese patients. For each study, efficacy outcome data from induction (weeks 6-12) and maintenance (weeks 30-60) treatment were extracted for analysis. Treatment effects on clinical response, clinical remission, and mucosal healing relative to the average placebo results across all trials were estimated using network meta-analyses followed by transformation into probabilities and odds ratios (OR). RESULTS: At the end of induction, the likelihood of clinical response and clinical remission was highest with infliximab (OR: 2.12 and 2.35, respectively) and vedolizumab (OR: 2.10 and 2.32, respectively); the likelihood of mucosal healing was highest with infliximab (OR: 2.24) and adalimumab (OR: 1.86). During maintenance, the likelihood of clinical response and clinical remission was highest with vedolizumab (OR: 6.44 and 4.68, respectively) and golimumab (OR: 5.13 and 3.84, respectively); the likelihood of mucosal healing was significantly higher than placebo with all biologics. CONCLUSIONS: All active treatments were efficacious compared with placebo. Infliximab and vedolizumab had the highest odds for induction of clinical response, remission, and mucosal healing. Golimumab and vedolizumab had numerically higher odds of achieving efficacy outcomes in the maintenance phase.

Risk of cardiac events with azithromycin-A prediction model.

Previous studies have suggested an increased risk of cardiac events with azithromycin, but the predictors of such events are unknown. We sought to develop and validate two prediction models to identify such predictors. We used data from Truven Marketscan Database (01/2009 to 06/2015). Using a split-sample approach, we developed two prediction models, which included baseline demographics, clinical conditions (Model 1), concurrent use of any drug (Model 1) and therapeutic class (Model 2) with a risk of QT-prolongation (CQT-Rx). Patients enrolled in a health plan for 365 days before and five days after dispensing of azithromycin (episodes). Cardiac events included syncope, palpitations, ventricular arrhythmias, cardiac arrest as a primary diagnosis for hospitalization including death. For each model, a backward elimination of predictors using logistic regression was applied to identify predictors in 100 random samples of the training cohort. Predictors prevalent in >50% of the models were included in the final model. A score for the Assessment of Cardiac Risk with Azithromycin (ACRA) was generated using the training cohort then tested in the validation cohort. A cohort of 20,134,659 episodes with 0.03% cardiac events were included. Over 60% included females with mean age of 40.1±21.3 years. Age, sex, history of syncope, cardiac dysrhythmias, non-specific chest pain, and presence of a CQT-Rx were included as predictors for Model-1 (c-statistic = 0.68). For Model-2 (c-statistic = 0.64), predictors included age, sex, anti-arrhythmic agents, anti-emetics, antidepressants, loop diuretics, and ACE inhibitors. ACRA score is available online (bit.ly/ACRA_2020). The ACRA score may help identify patients who are at higher risk of cardiac events following treatment with azithromycin. Providers should assess the risk-benefit of using azithromycin and consider alternative antibiotics among high-risk patients.

Comparison of Cardiac Events Associated With Azithromycin vs Amoxicillin.

Importance: Conflicting evidence exists on the association between azithromycin use and cardiac events. Objective: To compare the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data. Design, Setting, and Participants: This retrospective cohort study used data from Truven Health Analytics MarketScan database from January 1, 2009, to June 30, 2015. Patients receiving either amoxicillin or azithromycin and enrolled in a health care plan 365 days before (baseline period) the dispensing date (index date) were included in the study. Patients were matched 1:1 on high-dimensional propensity scores. Data were analyzed from October 1, 2018, to December 31, 2019. Exposures: New use of azithromycin compared with new use of amoxicillin. Main Outcomes and Measures: The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date. Logistic regression models were used to estimate odds ratios (ORs) with 95% CIs. Results: After matching, the final cohort included 2 141 285 episodes of each index therapy (N = 4 282 570) (mean [SD] age of patients, 35.7 [22.3] years; 52.6% female). Within 5 days after therapy initiation, 1474 cardiac events (0.03%) occurred (708 in the amoxicillin cohort and 766 in the azithromycin cohort). The 2 most frequent events were syncope (1032 [70.0%]) and palpitations (331 [22.5%]). The odds of cardiac events with azithromycin compared with amoxicillin were not significantly higher at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), and 30 days (OR, 0.98; 95% CI, 0.92-1.04). Among patients receiving any concurrent QT-prolonging drug, the odds of cardiac events with azithromycin were 1.40 (95% CI, 1.04-1.87) greater compared with amoxicillin. Among patients 65 years or older and those with a history of cardiovascular disease and other risk factors, no increased risk of cardiac events with azithromycin was noted. Conclusions and Relevance: This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently. Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.

Early Intervention With Vedolizumab on Longer Term Surgery Rates in Crohn's Disease: Post Hoc Analysis of the GEMINI Phase 3 and Long-term Safety Programs.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease that, with progression, may require surgical intervention. AIM: To determine whether vedolizumab treatment of CD earlier in the disease course (≤2 or ≤5 years disease duration) influences risk of CD-related surgery after accounting for probability of response. METHODS: Post hoc analyses of data from CD patients treated with vedolizumab in the GEMINI 2, GEMINI 3, and GEMINI LTS trials (N=1253) evaluated CD-related surgery (bowel resection or colectomy) with stratification by probability of response to vedolizumab (low/intermediate or high). Analyses used a previously validated clinical decision support tool and both logistic regression and Cox proportional hazard analyses. RESULTS: In total, 113 (9.0%) vedolizumab-treated patients required CD-related surgery. Surgical rates were 6.1% and 9.8% for the high and low/intermediate probability of response groups, respectively. Risk of surgery was lower for patients with a high probability of response versus those with a low/intermediate probability of response (HR 0.50; 95%CI 0.29 to 0.85). For patients with a low/intermediate probability of vedolizumab response, there was a consistent trend for association between earlier treatment (≤2 or ≤5 years since diagnosis) and a lower risk of surgery relative to later treatment (≤2 years versus >2 years: OR 0.77, 95%CI 0.38 to 1.58; ≤5 years versus >5 years: OR 0.61, 95%CI 0.37 to 1.00). CONCLUSIONS: Earlier intervention with vedolizumab may be associated with lower rates of surgery. Use of the clinical decision support tool may help identify patients most likely to benefit from earlier intervention with vedolizumab.

Prevalence of Cardiac Risk Factors in Patients Prescribed Azithromycin before and after the 2012 FDA Warning on the Risk of Potentially Fatal Heart Rhythms.

STUDY OBJECTIVE: To measure the prevalence of cardiac risk factors among patients prescribed azithromycin before and after the United States Food and Drug Administration (FDA) issued a warning on May 17, 2012, on the risk of potentially fatal heart rhythms associated with the drug. DESIGN: Retrospective cohort study using administrative claims data. DATA SOURCE: Truven Health Analytics MarketScan database. PATIENTS: A total of 12,971,078 unique patients with 23,749,652 azithromycin prescriptions dispensed between January 2009 and June 2015 were included. Patients had to be continuously enrolled in a health plan for at least 365 days (baseline) before the date of azithromycin dispensing (index date). Cohorts were assigned based on the index dates of the azithromycin prescriptions, either before (January 1, 2009-May 1, 2012) or after (June 1, 2012-June 30, 2015) the FDA warning was issued. MEASUREMENTS AND MAIN RESULTS: A cardiac risk factor included either a cardiac condition (heart failure or dysrhythmias) or concurrent use of drugs that prolong the QT interval. The unit of analysis was each prescription of azithromycin. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the prevalence of cardiac risk factors. Mean age of the patients was 40.1 ± 21.3 years old, with 60.8% females. Prior to the FDA warning, 11,596,022 (48.8%) azithromycin prescriptions were identified, and 12,153,630 (51.2%) were identified after the warning. The prevalence of a preexisting cardiac condition was 7.3% versus 7.9% (p<0.0001) before and after the FDA warning, respectively. Concurrent use of a QT-interval-prolonging drug was 23.3% versus 24.2% (p<0.0001) before and after the FDA warning, respectively. After controlling for confounders, the odds of having a cardiac risk factor after the FDA warning were significantly lower (odds ratio 0.938, 95% CI 0.936-0.940) compared with before the FDA warning. CONCLUSION: Despite the 2012 FDA warning, a nontrivial number of azithromycin prescriptions was prescribed concurrently in patients with preexisting a cardiac condition (1 of 12 azithromycin prescriptions) and in those using a QT-interval-prolonging drug (1 of 5 azithromycin prescriptions). After adjusting for confounders, the odds of cardiac risk factors being present in patients prescribed azithromycin were modestly lower after the warning; however, the prevalence remained essentially unchanged before and after the FDA warning was issued.

Prevalence of anal fistula in the United Kingdom.

BACKGROUND: Anal fistula is a pathological connection between the anal canal and perianal skin, which most commonly develops from an infected anal crypt. While the majority of anal fistulas are idiopathic, they are also associated with Crohn's disease (CD) and other inflammatory conditions. The prevalence of anal fistula is estimated to be 1-2 per 10000 patients, but population-based studies on anal fistula epidemiology are limited and outdated. AIM: To assess the prevalence of anal fistula and relevant comorbidities, with and without CD in the United Kingdom and Europe. METHODS: A retrospective population-representative observational cohort study was performed in The Health Improvement Network (THIN), a United Kingdom primary care database. Mid-year point prevalence of anal fistula was calculated on the first of July for each year between 2014 and 2017. Estimates were calculated for anal fistula overall and by CD status and standardized to the United Kingdom and European population. Prevalence of relevant comorbidities including lymphogranuloma venereum, hidradenitis suppurativa, anal presentation of sexually transmitted diseases, diabetes mellitus, and radiation in the pelvic area was reported. RESULTS: The United Kingdom-standardized overall point prevalence of anal fistula was 1.80 (95%CI: 1.65-1.94) per 10000 patients in 2017, while the Europe standardized estimate was 1.83 (95%CI: 1.68-1.98) per 10000 patients. Both these standardized point prevalence estimates ranged from 1.89 to 2.36 between 2014-2016. The United Kingdom-standardized point prevalence of anal fistula without CD was 1.35 (95%CI: 1.23-1.48) per 10000 patients, while the Europe-standardized estimate was 1.39 (95%CI: 1.26-1.52) per 10000 patients. In contrast, the standardized point prevalence estimate of anal fistula with CD was lower for both United Kingdom and Europe (0.44; 95%CI United Kingdom: 0.37-0.52, 95%CI Europe: 0.37-0.51) per 10000 patients in 2017. In 2017, 19% of anal fistula patients without CD and 13% of anal fistula patients with CD had at least one relevant comorbidity. These results show that anal fistulas are infrequent in the general population. 24.5% of prevalent anal fistulas are associated with CD, but other potentially etiological comorbidities are rare. CONCLUSION: This real-world evidence study estimated the United Kingdom-standardized prevalence of anal fistula was 1.80 per 10000 patients in 2017. Approximately 25% of cases may be associated with CD, while other comorbidities are rare.

No increased risk of nephrotoxicity associated with 5-aminosalicylic acid in IBD: a population-based cohort and nested case-control study.

BACKGROUND: There is conflicting evidence about nephrotoxicity risk associated with 5-aminosalicylates for treatment of IBD. AIMS: To determine population-based temporal trends for 5-aminosalicylates and estimated risk of nephrotoxicity associated with 5-aminosalicylate use for ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Retrospective cohort and nested case-control study, using the Health Improvement Network primary care database linked to hospital discharge coding for patients in England, 1996-2017. Nephrotoxicity risk analysis was a first recorded renal impairment diagnosis adjusted for key variables and was assessed between 2008 and 2017. RESULTS: A total of 35 601 patients with prevalent UC or CD were included. The proportion of patients prescribed 5-aminosalicylates fell from 83% in 1996-1999 to 71% in 2012-2015 for UC patients and 64% to 45% for CD patients. Thirty per cent of patients had prolonged 5-aminosalicylate use. Between 2008 and 2017, the incident rate of nephrotoxicity was similar and stable for UC (12.6/1000 person-years) and CD (10.9/1000 person-years) patients. Multivariate analysis showed no evidence for association between current prescription of 5-aminosalicylate and nephrotoxicity in UC or CD patients, comparing ≤ 30 days prescription prior to index vs 31-≤180 days. However, active disease, disease duration, concomitant cardiovascular disease or diabetes and nephrotoxic drug use were independently associated with development of nephrotoxicity in UC and CD. CONCLUSIONS: Despite the paucity of evidence for their benefit, 5-aminosalicylates were prescribed to approximately half of CD patients (30% prolonged therapy). Nephrotoxicity was rare in this patient cohort, and was not associated with 5-aminosalicylate use, but rather with disease status, comorbidity and use of nephrotoxic drugs.

The number needed to treat and relevant between-trial comparisons of competing interventions.

The number needed to treat (NNT) is considered an intuitive as well as popular effect measure. The aims of this review were to 1) explain why we cannot compare trial-specific NNT estimates for the competing treatments evaluated in different randomized controlled trials (RCTs) and 2) outline the principles of how relative treatment effects of different trials can be compared and results can be presented as NNT, without violating the principles of valid between-trial comparisons. Our premise is that ratio measures for relative treatment effects of response outcomes are less prone to effect modification than absolute difference measures of response outcomes. Accordingly, any between-trial comparisons of the efficacy of competing interventions using the study-specific ORs are less likely to be invalid or biased than comparisons based on the study-specific NNT estimates. However, treatment-specific ORs obtained from a meta-analysis or taken directly from an individual study can be transformed into consistent treatment-specific NNT estimates that allow for credible comparisons of treatments when these ratio measures are applied to the same reference response estimate. The theoretical discussion is illustrated with a relevant indirect comparison of biologics for the treatment of ulcerative colitis. Between-trial comparisons directly based on the NNT of individual trials may result in erroneous conclusions and should be avoided. Treatment-specific NNT estimates need to be based on the same probability of response with the common reference treatment against which the interventions are compared.

Burden and outcomes for complex perianal fistulas in Crohn's disease: Systematic review.

AIM: To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn's disease (CD) patients with complex perianal fistulas. METHODS: PubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016). RESULTS: Of 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD. CONCLUSION: Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is refractory to treatment in one-half of patients. AIMS: To evaluate the occurrence of suboptimal therapy among patients with IBD treated with tumor necrosis factor antagonists (anti-TNFs). METHODS: A multinational chart review in Europe and Canada was conducted among IBD patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who initiated anti-TNF therapy between 2009 and 2013. The primary endpoint was the cumulative incidence of suboptimal therapy during a two-year follow-up period, defined by the presence of the following indicators: dose escalation, discontinuation, switching, non-biologic therapy escalation, or surgery. RESULTS: The study included 1195 anti-TNF initiators (538 UC and 657 CD). The majority of patients (64% of UC and 58% of CD) had at least one indicator of suboptimal therapy. The median time to suboptimal therapy indicator was 12.5 and 17.5 months for UC and CD patients, respectively. Among the 111 UC and 174 CD anti-TNF switchers, 51% and 56% had an indicator of suboptimal therapy, respectively. The median time to suboptimal therapy indicator with the second anti-TNF was 14.3 and 13.0 months for UC and CD patients, respectively. CONCLUSION: The majority of IBD patients showed suboptimal therapy with current anti-TNFs.

Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohn's disease in the United States.

This study assessed the occurrence of indicators for suboptimal biologic therapy among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the United States (US). Data from a large US claims database (2005-2013) were used to retrospectively identify patients with diagnosed with either UC or CD who were new biologic users. Indicators of suboptimal biologic therapy included: dose escalation during the maintenance phase, discontinuation of the initial biologic, switch to another biologic within 90 days following the last day of supply of the initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD-related surgery, UC- or CD-related urgent care, and development of fistula (for CD only). Kaplan-Meier analyses were used. A total of 1,699 UC and 4,569 CD patients were included. Among UC patients, 51.1% and 90.9% experienced ≥1 indicator of suboptimal biologic therapy within 6 months and 36 months of biologic therapy initiation, respectively. Among CD patients, 54.3% and 91.4% experienced ≥1 indicator of suboptimal biologic therapy within 6 and 36 months of biologic therapy initiation, respectively. For both UC and CD patients, the most frequent indicators of suboptimal biologic therapy were discontinuation, dose escalation and augmentation. In conclusion, this study found that the occurrence of suboptimal biologic therapy is common among patients with UC and CD, with approximately 90% of patients experiencing at least one indicator of suboptimal biologic therapy within 36 months of biologic treatment initiation.