OBJECTIVESEvaluate the clinical utility of a precision-guided dosing test for infliximab (IFX) and its impact on treatment decision-making for inflammatory bowel disease (IBD).STUDY ...DESIGNProspective, multisite, clinical experience program.METHODSHealth care providers were given access to PredictrPK IFX, a precision-guided dosing test, for their patients with IBD on maintenance IFX therapy. Blood samples were drawn 20 to 56 days post infusion. A Bayesian data assimilation tool used clinical and serologic data to generate individual pharmacokinetic profiles and forecast trough IFX. Results were reported to providers to aid in-therapy management decisions and the decision-making process was assessed through questionnaires. Relationships between forecasted IFX concentration, disease activity, and therapy management decisions were analyzed by logistic regression.RESULTSPredictrPK IFX was used for 275 patients with IBD by 37 providers. In 58% of cases, providers modified treatment plans based on the results, including dose modifications (41%; of these, one-third decreased dose) and discontinuation (8%) of IFX. Of the 42% where treatment was not modified, 97.5% had IFX levels of 5 µg/mL or greater. Patients with IFX concentrations less than 5 µg/mL were 3 and 7.3 times more likely to have active disease or discontinue IFX, respectively. There was unanimous agreement among providers who completed a postprogram survey that PredictrPK IFX was beneficial in guiding treatment decisions and added more value to their practice than routine therapeutic drug monitoring.CONCLUSIONSPredictrPK IFX enables earlier and more precise dose optimization of IFX in patients with IBD, exerting a substantial impact on treatment decisions that may result in improved health outcomes and overall cost savings.
Pediatric inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), can result in significant morbidity requiring frequent health care utilization. Although it ...is known that the overall financial impact of pediatric IBD is significant, the direct out-of-pocket (OOP) cost burden on the parents of children with IBD has not been explored. We hypothesized that affected children with a more relapsing disease course and families in lower income strata, ineligible for need-based assistance programs, disparately absorb ongoing financial stress.
We completed a cross-sectional analysis among parents of children with IBD residing in California using an online HIPAA-secure Qualtrics survey. Multicenter recruitment occurred between December 4, 2013 and September 18, 2014 at the point-of-care from site investigators, informational flyers distributed at regional CCFA conferences, and social media campaigns equally targeting Northern, Central, and Southern California. IBD-, patient-, and family-specific information were collected from the parents of pediatric patients with IBD patients younger than 18 years of age at time of study, carry a confirmed diagnosis of CD or UC, reside in and receive pediatric gastroenterology care in California, and do not have other chronic diseases requiring ongoing medical care.
We collected 150 unique surveys from parents of children with IBD (67 CD; 83 UC). The median patient age was 14 years for both CD and UC, with an overall 3.7 years (SD 2.8 yr) difference between survey completion and time of IBD diagnosis. Annually, 63.6%, 28.6%, and 5.3% of families had an OOP cost burden >$500, >$1000, and >5000, respectively. Approximately one-third (36.0%) of patients had emergency department (ED) visits over the past year, with 59.2% of these patients spending >$500 on emergency department copays, including 11.1% who spent >$5000. Although 43.3% contributed <$500 on procedure and test costs, 20.0% spent >$2000 in the past year. Families with household income between $50,000 and $100,000 had a statistically significant probability (80.6%) of higher annual OOP costs than families with lower income <$50,000 (20.0%; P < 0.0001) or higher income >$100,000 (64.6%; P < 0.05). Multivariate analysis revealed that clinical variables associated with uncontrolled IBD states correlated to higher OOP cost burden. Annual OOP costs were more likely to be >$500 among patients who had increased spending on procedures and tests (odds ratio OR, 5.63; 95% confidence interval CI, 2.73-11.63), prednisone course required over the past year (OR, 3.19; 95% CI, 1.02-9.92), at least 1 emergency department visit for IBD symptoms (OR, 2.84; 95% CI, 1.33-6.06), at least 4 or more outpatient primary medical doctor visits for IBD symptoms (OR, 2.82; 95% CI, 1.40-5.68), and history of 4 or more lifetime hospitalizations for acute IBD care (OR, 2.60; 95% CI, 1.13-5.96).
Previously undocumented, a high proportion of pediatric IBD families incur substantial OOP cost burden. Patients who are frequently in relapsing and uncontrolled IBD states require more acute care services and sustain higher OOP cost burden. Lower middle income parents of children with IBD ineligible for need-based assistance may be particularly at risk for financial stress from OOP costs related to ongoing medical care.
Abstract Objectives Medical and surgical approaches toward children with ulcerative colitis (UC) vary and have differing implications for health care use. The goal of this study was to define ...hospital use and complications for children with UC before and after staged restorative proctocolectomy. Patients and Methods A retrospective study of the California Patient Discharge Dataset from 1999 to 2007 of children aged 2 to 18 years with UC who underwent colectomy was performed (N = 218). Surgical staging was determined alongside hospital type (children's vs non-children's) and surgical case volume. Postoperative complications and hospital length of stay were analyzed using multivariate regression. Results The cohort was mostly male (56%) and white (80%), had private insurance (78%), and underwent colectomy at a children's hospital (62%). Overall, 65% required a separate hospital admission before admission for colectomy. Single-, 2-, and 3-stage procedures were performed in 19 (9%), 144 (66%), and 38 (17%) children. The mean admissions per patient were 1.8 ± 2.4 before colectomy and 0.7 ± 1.6 after surgical completion. Surgical complications occurred in 100 (49%) children, with 39% being attributed to postoperative infection. Children with public insurance (odds ratio, 2.18; 95% confidence interval, 1.0-4.85) and those who underwent colectomy at a non–children's hospital (odds ratio, 2.53; 95% confidence interval, 1.0-6.37) had increased likelihood of surgical complications. Finally, nonwhite race, surgical staging, and undergoing colectomy at a low- or medium-volume hospital resulted in prolonged hospitalization ( P < .05). Conclusions Children with UC who undergo colectomy use a large number of hospital resources before surgery and exhibit decreased hospital use after surgical completion. Children undergoing colectomy at children's and high-volume hospitals experience fewer surgical complications and shorter hospitalization.
ABSTRACT
Purpose:
To evaluate tacrolimus in 3 situations: for the induction of remission in children with severe steroid‐resistant ulcerative colitis (UC); for steroid sparing in children with ...steroid‐dependent UC in whom treatment with other immunosuppressants fails; and for the maintenance of remission in children with steroid‐dependent and steroid‐resistant UC.
Patients and Methods:
We retrospectively evaluated 18 consecutive patients (13 with pancolitis) who were treated with oral tacrolimus at our institution from May 1999 to October 2005. Nine patients had steroid‐resistant UC and 9 patients were steroid‐dependent. We started patients initially on tacrolimus 0.2 mg/kg divided twice daily, with a goal plasma trough level of 10 to 15 ng/mL for the first 2 weeks, and then titrated doses to achieve plasma levels between 7 and 12 ng/mL after induction.
Results:
Of the 18 patients in this study, 17 showed a positive response to tacrolimus therapy (ie, cessation of diarrhea and other symptoms) and 5 showed a prolonged response to tacrolimus. The mean time from initiation of tacrolimus therapy until response was 8.5 days. The mean duration of response was 260 days. Eleven of 18 patients required colectomy, including all of the patients with steroid‐resistant UC, but only 2 of 9 who were steroid‐dependent. The mean time from initiation of tacrolimus until colectomy was 392 days.
Conclusions:
It is possible that tacrolimus may benefit selected patients with steroid‐dependent UC, including those who are intolerant of 6‐mercaptopurine or azathioprine. Conversely, patients with steroid‐resistant UC are unlikely to sustain a prolonged clinical response to tacrolimus and seem to require colectomy eventually. Careful considerations of risk versus benefit, as well as close monitoring for adverse effects, are essential in all patients.
ABSTRACT
Objectives:
Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical ...predictors associated with surgery in children with UC using a disease‐specific database.
Methods:
Children diagnosed with UC at age <18 years were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999 to November 2003 were extracted alongside incidence and surgical staging.
Results:
Review of the PediIBDC database identified 406 children with UC. Approximately half were girls (51%) with an average age at diagnosis of 10.6 ± 4.4 years in both boys and girls. Average follow‐up was 6.8 (±4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (interquartile range 4.9) years after initial diagnosis. Children presenting with weight loss (hazard ratio HR 2.55, 99% confidence interval CI 1.21–5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15–17.04) at time of diagnosis and children with a first‐degree relative with UC (HR 1.81, 99% CI 1.25–2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90–9.57) or tacrolimus (HR 3.66, 99% CI 1.60–8.39) also required earlier surgical management. Other symptoms, laboratory tests, and medical therapies were not predictive for need of surgery.
Conclusion:
Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC, and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis.
Probiotic strains of Lactobacillus are currently used in a variety of clinical practices with limited evidence to support their use. Lactobacillus species are a normal part of gastrointestinal flora, ...and bacteremia with probiotic strains of Lactobacillus is very uncommon. We describe a case of Lactobacillus bacteremia in a 17-year-old boy with ulcerative colitis managed with systemic corticosteroids and infliximab, who presented with fever to 102°F, flushing, and chills 1 week after starting Lactobacillus rhamnosus GG probiotics. Initial blood culture on day 2 of his fever was positive for Lactobacillus, however, subsequent blood cultures on day 3 and 5 were negative. He was treated empirically with antibiotics for 5 days and defervesced by day 8 of his illness. 16 S rRNA sequence analysis identified the organism from the patient’s blood culture and probiotic capsule as L. rhamnosus with a 99.78% match for both the strains. This case report highlights the potential risk of Lactobacillus bacteremia in immunosuppressed patients with severe active ulcerative colitis.
Summary Background Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk ...for complications are not available, and the effect of treatment on risk is unknown. Methods We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. Findings Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51–82) and specificity of 63% (55–71), with a negative predictive value of 95% (94–97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio HR 0·30, 95% CI 0·10–0·89; p=0·0296) but not stricturing complication (1·13, 0·51–2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12–2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%. Interpretation Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy. Funding Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
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