Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis.

BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial. METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed. RESULTS: A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer. CONCLUSIONS: Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab. (Funded by Eli Lilly; LUCENT-1 and LUCENT-2 ClinicalTrials.gov numbers, NCT03518086 and NCT03524092, respectively.).

Use, Durability, and Risks for Discontinuation of Initial and Subsequent Biologics in a Large Pediatric-Onset IBD Cohort.

BACKGROUND: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic. METHODS: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation. RESULTS: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8-3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC ( P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date. CONCLUSIONS: Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.

Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Vedolizumab, a humanized monoclonal antibody against α4ß7 integrin, is used to treat adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). We investigated the time course of clinical response to vedolizumab in patients who were and were not previously treated with tumor necrosis factor (TNF) antagonists. METHODS: We performed a post-hoc analysis of data from phase 3, randomized, controlled trials of vedolizumab vs placebo in adult patients with UC (N = 374) or CD (N = 784). We collected data on patient-reported symptoms (rectal bleeding and stool frequency for patients with UC, abdominal pain and loose stool frequency for patients with CD) reported at weeks 2, 4, and 6 of treatment. We reported mean percentage score changes from baseline and proportions of patients who achieved predefined scores. We performed multivariate logistic regression analysis to identify factors associated with an early response (at week 2). RESULTS: In patients with UC (overall or naive to TNF antagonist therapy), a significantly greater percentage of patients given vedolizumab achieved the predefined composite symptom score at weeks 2, 4, and 6 compared to those given placebo. In patients with CD who were naive to TNF antagonists, a significantly greater percentage of patients given vedolizumab achieved the predefined score at weeks 2 and 4 compared to those given placebo. Among patients with UC given vedolizumab, 19.1% (overall) and 22.3% (TNF antagonist naive) achieved a composite score of rectal bleeding of 0 and stool frequency ≤1 at week 2 compared to 10% (overall) and 6.6% (TNF antagonist naive) of those receiving placebo. Among TNF antagonist-naive patients with CD, 15.0% of those given vedolizumab achieved an average daily composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 (compared to 7.9% given placebo), and 23.8% of those given vedolizumab achieved these by week 4 (compared to 10.3% given placebo). CONCLUSIONS: In a post-hoc analysis of data from phase 3 clinical trials, vedolizumab significantly improved patient-reported symptoms of UC and CD as early as week 2 of treatment, continuing through the first 6 weeks-especially when given as first-line biologic therapy. ClinicalTrials.gov no: NCT00783718, NCT00783692, NCT01224171.

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review.

OBJECTIVES: In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program proposed shifting the therapeutic focus on ulcerative colitis (UC) toward altering the natural history of the disease course by regularly monitoring objective measurements of disease activity and tailoring treatment accordingly. The therapeutic paradigm shift was well received in the research community and is often cited. However, new evidence on optimal UC treatment targets continues to accumulate since the time of the STRIDE guidelines. This systematic review summarizes the evidence accrued since the STRIDE UC recommendations, discusses the barriers for adoption of treat-to-target approaches in clinical practice in UC, and suggests directions for future research. METHODS: We systematically reviewed MEDLINE for studies from the time of the STRIDE systematic review up to March 31, 2018, that assessed the potential treatment targets identified by the STRIDE recommendations. RESULTS: Each potential treatment target literature search returned > 200 articles, which were then reviewed by 2 independent investigators for relevant studies. Selected studies of clinical factors, patient-reported outcomes, endoscopy, histology, imaging, and biomarkers and implications on treatment targets are summarized. CONCLUSIONS: It appears that the relative weight given to different therapeutic targets in the development and improvement of UC treatments could be optimized, with an increased emphasis on endoscopic and histological targets over clinical or symptomatic targets. For this evolution to occur, however, new research has to demonstrate that the treat-to-target approach will deliver on the promise of better long-term outcomes compared with current approaches.

Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes.

BACKGROUND AND AIMS: To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC]. METHODS: Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR. RESULTS: Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p <0.001], irrespective of prior biologic/tofacitinib failure [p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p <0.05]; ER at W12 was associated with clinical remission [CR] [p <0.05] and corticosteroid-free remission [CSFR] at W40 [p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [p <0.05]. CONCLUSIONS: Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.

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.

Psychometric evaluation of the Urgency NRS as a new patient-reported outcome measure for patients with ulcerative colitis.

BACKGROUND: The Urgency Numeric Rating Scale (NRS) was developed as a content-valid single-item patient-reported outcome measure to assess severity of bowel urgency. Here, we evaluated the psychometric properties of the Urgency NRS. METHODS: Data were from a multicenter, randomized, placebo-controlled phase 3 trial in adults with moderately to severely active ulcerative colitis (NCT03518086). Patients completed the Urgency NRS using a daily electronic diary, from which weekly average Urgency NRS scores were calculated. Test-retest reliability, known-groups validity, construct validity, responsiveness, and score interpretation were assessed using the modified Mayo score, Inflammatory Bowel Disease Questionnaire (IBDQ), Patient Global Rating of Severity (PGRS), Patient Global Rating of Change (PGRC), and Geboes score. RESULTS: The study sample comprised 1,162 participants (40.2% female). Mean Urgency NRS score was higher (worse) at baseline than at week 12 (6.2 vs. 3.7). Test-retest reliability was strong, with intra-class correlation coefficients of 0.76-0.89. Baseline least-square mean Urgency NRS score was higher for participants with a PGRS score greater than the median (worse symptoms) than for those with a PGRS score less than or equal to the median (7.5 vs. 5.4; p < 0.0001), indicating good known-groups validity. Urgency NRS score was moderately correlated with IBDQ total and domain scores, PGRS, PGRC, and modified Mayo stool frequency, establishing its convergent validity. Correlations were weak for Geboes score and weak to moderate for modified Mayo endoscopic subscore and modified Mayo rectal bleeding, indicating that the Urgency NRS also had discriminant validity. Patients achieving clinical remission, clinical response, IBDQ remission, and PGRS score improvement showed significantly greater improvement on the Urgency NRS (p < 0.0001 for all), demonstrating responsiveness to change. A ≥ 3-point improvement in Urgency NRS score represented a meaningful improvement in bowel urgency and an Urgency NRS score of ≤ 1 point represented a bowel urgency remission threshold that was closely associated with clinical, endoscopic, and histologic remission. CONCLUSIONS: The Urgency NRS is a valid and reliable patient-reported outcome measure that is suitable for evaluating treatment benefits in clinical trials in patients with moderately to severely active ulcerative colitis.

Development and Validation of an Inflammatory Bowel Disease Severity Index Using US Administrative Claims Data: A Retrospective Cohort Study.

BACKGROUND: Clinical indices to characterize the severity of inflammatory bowel disease (IBD) are widely used in clinical trials and real-world practice. However, there are few validated instruments for assessing IBD severity in administrative claims-based studies. METHODS: Patients (18-89 years) diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and receiving ≥1 prescription claim for IBD therapy were identified using administrative claims data from the Optum Clinformatics, IMS PharMetrics, and Truven MarketScan databases (January 1, 2013-September 30, 2017). Regression modeling identified independent predictors of IBD-related hospitalization (inpatient stay or emergency department visit resulting in hospitalization), which were used to develop IBD severity indices. The index was validated against all-cause hospitalization and total cost and IBD-related hospitalization and total cost. RESULTS: There were 51,767 patients diagnosed with UC (n = 30,993) or CD (n = 20,774) who were initiated treatment with IBD therapy. Independent predictors of IBD-related hospitalization were Charlson Comorbidity Index score >1, anemia, weight loss, intravenous corticosteroid use, prior gastrointestinal-related emergency department visit and hospitalization, and unspecified disease location or more extensive disease. Female sex, renal comorbidities, intestinal fistula, and stricture were additional risk factors for patients with CD, whereas age <40 years was a UC-specific risk factor. Median IBD severity scores were 8 and 13 for UC and CD, respectively, from possible total scores of 51 and 37. Inflammatory bowel disease severity score correlated with significantly higher all-cause hospitalization and cost, all-cause total cost, IBD-related hospitalization cost, and total cost. CONCLUSIONS: These validated UC and CD severity indices can be used to predict IBD-related outcomes using administrative claims databases.

Risk of Infection and Types of Infection Among Elderly Patients With Inflammatory Bowel Disease: A Retrospective Database Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) treatment in the elderly is challenging in part because of increased risk of infections. The aim of our study was to determine the absolute and relative risk of infections among the elderly IBD patient population and to identify factors affecting the risk of infections in the overall IBD patient population. METHODS: A retrospective study of patients with IBD initiating corticosteroids, immunomodulators (IM), or biologic therapy (January 2010-December 2014) was conducted using the Truven Market Scan database. IM and biologic exposure were assessed in a time-dependent manner. ICD-9 codes identified infection during follow-up. A Cox proportional hazards model was fitted to gauge the association between age, other covariates, and infection risk. RESULTS: We identified 63,759 patients with IBD. We found 2664 infections (incidence rate [IR] = 16.95/100 person-years) among 8788 elderly patients with IBD and 10,515 (IR = 10.49/100 person-years) among the nonelderly group. Pneumonia (39.8%), sepsis (13.2%), and candidiasis (12.9%) were the most common infections in the elderly. Factors associated with a higher risk of infection included being elderly (HR: 1.27, P < 0.0001), anti-TNF therapy (HR: 1.64, P < 0.0001), IM therapy (HR: 1.32, P < 0.0001), and polypharmacy (HR: 1.32, P < 0.0001). CONCLUSIONS: Advanced age, anti-TNF (biologic) therapy, and IM therapy were associated with an increased risk of infection. Pneumonia was the most common infection among the elderly IBD population. Physicians should be mindful of these risks when prescribing medications for elderly patients with IBD, and ensure their patients are adequately vaccinated.

Retrospective Claims Analysis Indirectly Comparing Medication Adherence and Persistence Between Intravenous Biologics and Oral Small-Molecule Therapies in Inflammatory Bowel Diseases.

INTRODUCTION: Patients' adherence to and persistence on treatment for inflammatory bowel disease (IBD) can vary, depending on type and distribution of disease and treatment modality. We aim to identify differences in adherence and persistence with treatments with different administration routes (intravenous vs oral) in IBD. METHODS: A retrospective cohort analysis of a claims database of adult patients diagnosed with IBD or rheumatoid arthritis (RA) who began treatment with vedolizumab, tofacitinib, or infliximab from January 2015 through December 2015. Adherence evaluated by proportion of days covered (PDC) and cumulative days with gaps at least 20% beyond expected interval (CG20) using multivariable generalized linear equation models. Persistence assessed as time to treatment discontinuation over 12 months of follow-up using Kaplan-Meier estimates and Cox proportional hazards models; proportion of persistent patients determined via multivariable logistic regression. Indirect comparisons across disease states adjusted using infliximab data. RESULTS: After indirect adjustment by disease, mean PDC difference was significantly higher (difference of 4.7%; P = 0.0376) and mean CG20 was lower (difference of 15 days; P = 0.0646) but not statistically significant in vedolizumab/IBD than tofacitinib/RA. CONCLUSION: We describe a novel adjustment method for interdisease treatment differences using infliximab treatment patterns to bridge differences between IBD and RA. After adjustment, adherence was higher with infusions than oral medications, which may affect outcomes. Indirect comparisons between vedolizumab and tofacitinib are not generalizable and should be confirmed in tofacitinib-treated IBD patients. FUNDING: Takeda Pharmaceuticals U.S.A., Inc.

Infusion administration billing for vedolizumab and infliximab in inflammatory bowel disease.

AIMS: Increasing use of biologics has led to interest in treatment components with potential for cost savings. This study was aimed at comparing administration times and associated costs of infliximab and vedolizumab infusions for inflammatory bowel disease (IBD). MATERIALS AND METHODS: This study used claims data from the Symphony Health Integrated Dataverse to identify IBD patients using infliximab or vedolizumab between 20 May 2014 and 29 February 2016. Use of Current Procedural Terminology administration codes was evaluated and costs calculated using the 2016 Center for Medicare and Medicaid Services Physician Fee Schedule. Assessments included infusion times, associated costs, productivity loss using average wage estimates from the United States Bureau of Labor Statistics, and home infusion adoption. RESULTS: A total of 10,051 infliximab and 3114 vedolizumab patients with first-hour claims were identified; 52.0% were female and 64.5% had Crohn's disease. There were 48,377 infliximab first-hour claims (mean 4.8 infusions per patient); 46,462 (96.0%) had a second-hour claim. In comparison, there were 14,717 vedolizumab claims (mean 4.7 infusions per patient), with only 411 (2.8%) second-hour claims, resulting in vedolizumab cost savings of approximately $1.27 million. The difference in second-hour infusions resulted in 46,051 additional hours of productivity loss with infliximab, and lost wages averaging $1.18 million (range $0.68-$1.77 million). LIMITATIONS: Administration costs were inferred as charge costs and not directly assessed. Productivity loss assessed time spent on infusion only, and included a small proportion of patients beyond working age. CONCLUSIONS: Second-hour infusion billing was significantly lower with vedolizumab than with infliximab, corresponding to cost savings and reduced productivity loss.

Risk factors for postoperative infection after gastrointestinal surgery among adult patients with inflammatory bowel disease: Findings from a large observational US cohort study.

BACKGROUND AND AIM: Postoperative infection (POI) is a major source of morbidity and prolongation of hospitalization in inflammatory bowel disease (IBD) patients. This large observational study was conducted to further describe risk factors and to quantify the proportion of POIs that are preventable. METHODS: We conducted a retrospective cohort analysis of the Optum US health insurance claims database. The study population included adults with ulcerative colitis (UC) or Crohn's disease (CD) who underwent lower gastrointestinal (GI) surgery of small intestine, colon, rectum, or anus during September 2014 to September 2016. Multiple logistic regression was used to identify and quantify risk factors and determine the proportion of infections that are preventable. RESULTS: A total of 3360 adult IBD patients with lower GI surgery were included in the study. Their mean age was 51 years, 52.5% were women, and 59.5% had CD. The 30-day POI incidence was 15.1% (95% confidence interval: 14.0-16.4%). We identified the following nonmodifiable or procedural risk factors: history of POI, open procedure, red blood cell transfusion within 6 months, preoperative hospital stay of at least 4 days, lower GI ostomy surgery, lower GI resection surgery, and a history of chronic obstructive pulmonary disease. Modifiable risk factors included corticosteroid use and anemia prior to surgery, but few infections were attributable to these modifiable factors. CONCLUSIONS: This large, observational, real-world evidence study from the US found that the majority of the observed risk factors were nonmodifiable or procedure-related. Corticosteroid use and anemia before surgery were identified as modifiable risk factors.

Efficacy of Vedolizumab in Fistulising Crohn's Disease: Exploratory Analyses of Data from GEMINI 2.

BACKGROUND AND AIMS: Medical management of fistulising Crohn's disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4ß7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692]. METHODS: Exploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates. RESULTS: At entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], -11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54-11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059-0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates. CONCLUSIONS: Our findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

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.

Risk of Malignancy in a Nationwide Cohort of Elderly Inflammatory Bowel Disease Patients.

BACKGROUND: Management of elderly inflammatory bowel disease (IBD) patients (≥ 65 years of age) is complicated due to many factors, including a higher risk of cancer, which may impact therapeutic decisions. OBJECTIVE: The aim of this study was to determine the risk of cancer among elderly IBD patients compared with younger IBD patients. Additionally, the absolute risk of malignancy and factors contributing to it were evaluated, and therapeutic patterns among the elderly were assessed. METHODS: This retrospective cohort study extracted data from the Truven Health Analytics MarketScan® database. Among adult IBD patients who were free of cancer before starting on corticosteroids, immunomodulators, or biologics, a Cox model for time to cancer was fitted that adjusted for several covariates, including time-dependent treatment. Baseline results were evaluated by age group, as were the incidence of cancer and the distribution of cancer subtypes. RESULTS: The elderly IBD cohort (n = 8788) had a higher prevalence of cancer and several other ailments before starting treatment, relative to the younger IBD cohort aged 18-64 years (n = 54,971). During follow-up, the elderly IBD cohort experienced a higher incidence of malignancy, confirmed by a hazard ratio (HR) of 3.04 (95% confidence interval [CI] 2.71-3.41) from the Cox model fit. The risk of cancer was also significantly associated with male sex (HR 0.82 female), duration of disease (HR 1.08), several comorbidities and corticosteroid use (HR 1.35), but not with the use of immunomodulators or biologics. Non-Hodgkin's lymphoma, urinary tract malignancy, and prostate, lung, and female breast cancers were observed more commonly in this elderly IBD cohort when compared with the same age group in the Surveillance, Epidemiology, and End Results (SEER) database. CONCLUSIONS: The elderly with IBD have a higher risk of malignancy when compared with younger IBD patients and the general age-matched population, with certain cancers being more common among these patients.

Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom.

Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts. We assessed PSC epidemiology and natural history within the UK Clinical Practice Research Datalink (CPRD).Incidence and natural history of PSC were evaluated in a retrospective cohort study using linkage of CPRD, Hospital Episode Statistics, and Office for National Statistics data. Data from age, sex, and general practice-matched population controls provided a context for the incident PSC patients. Liver disease other than PSC was defined as autoimmune hepatitis, hepatitis, hepatomegaly, liver failure, cirrhosis, portal hypertension, cholangiocarcinoma, or hepatobiliary cancer.The age-standardized incidence of PSC was 0.68 (95% confidence interval [CI] 0.45-0.99) per 100,000 person-years and the age-standardized prevalence was 5.58 (95% CI 4.82-7.35) per 100,000 during 1998 to 2014. In all, 250 incident PSC patients met the inclusion criteria and each was matched with 5 controls (mean age 54 ±â€Š18 years, men 63.2%). A higher percentage of PSC patients had a history of inflammatory bowel disease (54% vs 2%) and liver disease other than PSC (22% vs 1%) than controls (standardized differenceweighted >0.1). During a median follow-up of 5 years, PSC patients were more likely to develop adverse health outcomes. The mortality rate per 1000 person-years was 3-fold higher in PSC than population controls (49.5 vs 16.1; incidence rate ratio 3.1, 95% CI 2.2-4.2).The incidence and prevalence of PSC observed in the UK CPRD were either comparable with or higher than previous studies. Compared with the general population, PSC patients had worse health outcomes including PSC disease progression, complications, and higher mortality.