Search

Introduction: Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration. Methods: This phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect. Results: A total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference − 4 mm; 95% confidence interval: − 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed. Conclusions: The new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation. Trial Registration: ClinicalTrials.gov: NCT02986139. Funding: Amgen Inc, Thousand Oaks, CA USA. [ABSTRACT FROM AUTHOR]

Objective: Methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA) due to its effectiveness, tolerability, and cost. This study examines MTX prescribing practices in the US from 2009 to 2014.Methods: Symphony Health Solutions, which covers 274 million patients in the US, was used to identify patients diagnosed with RA who were naive to MTX in 2009 and 2012. Data were collected, including medication use and doses, demographics, and medical comorbidities.Results: Of the patients who had 5-year followup data available, oral MTX was started in 35,640 in 2009, and 44% continued taking this dose during the followup. Of the 20,041 patients who changed therapy during the study period, 87% had the addition of or switched to a biologic agent, while 13% were changed from oral to subcutaneous (SC) MTX. The mean oral dose prior to the start of a biologic agent was 15.3 ± 5 mg/week. A comparison of 2009 with 2012 showed a modest increase in the mean dose of oral MTX from 15.3 mg/week to 15.9 mg/week, as well as a small but statistically significant (P < 0.0001) increase in the use of SC MTX after failure of oral MTX from 13% to 16% of patients.Conclusion: MTX is underutilized in the treatment of RA with suboptimal dosing, inadequate duration of therapy, and failure to use SC administration. The comparison of MTX use between the 2009 and the 2012 cohorts demonstrates only a marginal increase in the dose of oral MTX and the use of SC MTX. [ABSTRACT FROM AUTHOR]

The author focuses on the exercise of theory construction in the books "Punishing the Poor" and "Prisons and Poverty" both by Loic Wacquant. He discusses the attempt of the author to warn European governments on the negative effects of U.S. policies. He explains the link of power to knowledge in the implementation of changes that exemplifies internal insecurity. He emphasizes the practice of think-tanks to circulate information on knowledge.

Background: Secondary stroke prevention guidelines recommend antithrombotic agents such as over-the-counter aspirin, prescription antiplatelet agents, or anticoagulant agents. Purpose: The study was designed to measure whether use of outpatient antithrombotic agents is increasing among stroke survivors. Methods: The sample consisted of 4168 people who self-reported cerebrovascular disease and who participated in the Medical Expenditure Panel Survey, an annual representative sample of the U.S., during the years 2000–2006. Use of antithrombotic agents was calculated from face-to-face interviews about the use of aspirin and from pharmacies about the use of prescription medications. Cochran–Armitage tests were used to detect temporal trends and multivariate models to identify predictors of use of antithrombotic agents. Results: Pooling results across the 7 years, it was found that 57% were taking aspirin, 66% were using any antiplatelet agent, and 75% were using any antithrombotic agent. After excluding people who said aspirin was unsafe, 81% were using any antithrombotic agent. During the study period, use of prescription antiplatelet agents increased (p<0.001) but there was no temporal change in use of antithrombotic agents overall. In multivariate models, being aged >65 years, male gender, non-Hispanic ethnicity, having a usual source of care, and poor or fair health status were associated with use of an antithrombotic agent (p<0.05). Conclusions: Although a high percentage of stroke survivors appear to use an antithrombotic agent, further research should investigate whether and how to improve care among the remaining 20% of stroke survivors, particularly among younger, female, and Hispanic patients. [Copyright &y& Elsevier]

To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis (OA) of the knee. A 6-week, randomized, parallel-group, double-blind, placebo-controlled study. One hundred thirteen outpatient sites in the United States. A total of 1,042 male and female patients aged 40 and older with OA of the knee (>6 months). Rofecoxib 12.5 mg once a day (n=424), nabumetone 1,000 mg once a day (n=410), or placebo (n=208) for 6 weeks. The primary efficacy endpoint was patient global assessment of response to therapy (PGART) over 6 weeks, which was also specifically evaluated over the first 6 days. The main safety measure was adverse events during the 6 weeks of treatment. The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib (55.4%) than nabumetone (47.5%; P=.018) or placebo (26.7%; P<.001 vs rofecoxib or nabumetone). Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib (2 days) than with nabumetone (4 days, P=.002) and placebo (>5 days, P<.001) (nabumetone vs placebo; P=.007). The safety profiles of rofecoxib and nabumetone were generally similar, including gastrointestinal, hypertensive, and renal adverse events. Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily. Both therapies were generally well tolerated. [ABSTRACT FROM AUTHOR]

Compares the safety and efficacy of leflunomide with placebo and methotrexate treatment in patients with active rheumatoid arthritis (RA). Study conducted on rheumatology practices in the United States and Canada; Improved signs and symptoms of active RA; Delayed disease progression; Improved function and health-related quality of life.

Focuses on the guidelines for employee participation in management decision-making in the U.S. Process of leadership theory and guided management and development; Movement of workplace from value orientation; Actors of participation levels. INSETS: Specific Goals;Need for Structure.

Discusses the features of economic censuses that are needed in projecting and analyzing the performance and prospects of individual companies and product lines in the U.S. Development of projections that show the relationship between capital investment and labor productivity; Analysis of geographic patterns for any industry; Ability of the census to manage inventories.

Focuses on ghetto consumers in the United States. Procedures proposed by the Federal Trade Commission concerning ghetto dwellers; Impact of the rising level of violence in the ghetto on opening up channels for the orderly distribution of goods.

The article offers information on the objectives of the International School Art Program (ISAP), an art education program in the U.S. The two main functions of ISAP include, to elevate friendly interest and understanding among young people in the world through the exchange of art work and to enhance their creative ability by using personal interests, experiences and feelings as subject matter. The author provides directions and goals for the program to achieve its purposes including, personal involvement in art work, employment of various appropriate materials and approaches to interpret subjects, and the recognition to the contribution of artists, art educators, administrators and parents.

The article profiles Joan M. Bathon who has accepted the editorship of the periodical on July 1, 2010. Bathon earned her bachelor of science degree at Marquette University in Milwaukee, Wisconsin with magna cum Laude. She is a professor of Medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland. She founded the John Hopkins Arthritis WebSite in 1998. She is also a recipient of various awards including the Mary Betty Stevens Award. Her plans for the periodical are noted.

Background and Aims: Autoimmune hepatitis (AIH) is a chronic, inflammatory disease of the liver with increasing prevalence. However, limited epidemiological data exist for the prevalence of AIH in the United States. We used a large database to describe the prevalence of AIH in the United States and the autoimmune diseases associated with it., Approach and Results: Data was collected from a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated health care systems in the United States. We identified a cohort of patients with a diagnosis of AIH from April 2014 to April 2019 based on a Systemized Nomenclature of Medicine-Clinical Terms and calculated the prevalence of AIH. Of the 37,161,280 individuals active in the database from April 2014 to 2019, we identified 11,600 individuals with a diagnosis of AIH with an overall prevalence rate of 31.2/100,000. The prevalence of AIH was increased in females compared with males [odds ratio (OR)=3.21, P<0.0001], elderly (aged above 65 y) compared with adults (aged 18 to 65 y) and children (aged below 18 y) (OR=2.51, P<0.0001) and whites compared with African Americans, Asians, and Hispanics (OR=1.12, P<0.0001). Moreover, patients with AIH were more likely to have Sjögren syndrome, systemic lupus erythematosus, ulcerative colitis, celiac disease, rheumatoid arthritis, Crohn's disease, and autoimmune thyroiditis as compared with patients without AIH., Conclusions: We found that the estimated prevalence of AIH in the United States is 31.2/100,000, which is comparable to the reported prevalence of AIH in Europe. We confirmed that AIH has a strong association with other autoimmune diseases studied in the literature., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation., Methods: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM ® MarketScan ® Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions., Results: In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses., Conclusion: These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA., Trial Registration: Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

Objective: To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic., Methods: A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by e-mail and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus., Results: To date, the task force has approved 80 guidance statements: 36 with moderate and 44 with high consensus. These were combined, resulting in 27 final guidance statements., Conclusion: These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated., (© 2020, American College of Rheumatology.)

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post-hoc pooled analysis assessed commonalities and differences in tofacitinib efficacy and safety for US versus rest of the world (ROW) populations., Methods: Pooled phase (P) III data from patients receiving tofacitinib 5 or 10 mg twice daily (BID) or placebo were assessed for efficacy at Month 3 and for safety outcomes over 12 months. For adverse events of special interest, data on tofacitinib 5 or 10 mg BID or placebo were pooled from six PII and five PIII randomised studies., Results: PIII data were available for 664 vs. 2447 and PII/PIII data for 943 vs. 3567 US vs. ROW patients, respectively. The US population had a higher proportion of Caucasians (81.5% vs. 54.4%), lower proportion of Asians (1.0% vs. 34.6%), and higher mean body weight (85.7 vs. 66.2 kg) and body mass index (31.5 vs. 25.6 kg/m2) compared with ROW. At Month 3, PIII efficacy was similar between US and ROW as assessed by ACR 20/50/70 response rates, remission rates (DAS 28-4[ESR]<2.6), and HAQ-DI scores. Diarrhoea, peripheral oedema, and upper respiratory tract infection occurred in >5% of PIII patients in the US population. Incidence rates for adverse events of special interest were similar between the US and ROW PII/PIII populations., Conclusions: Patients in the US achieved similar efficacy and safety with tofacitinib 5 and 10 mg BID compared with patients in ROW.

A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.

Background & Aims: Hepatic encephalopathy, a spectrum of neuropsychiatric abnormalities that can occur in patients with liver dysfunction, negatively affects driving performance, but no study has examined legal ramifications. We studied state requirements for reporting hepatic encephalopathy and investigated whether lawsuits have been completed against physicians or patients for motor vehicle accidents that were related to hepatic encephalopathy., Methods: We contacted motor vehicle departments from all 50 states and examined motor vehicle codes and legal databases to search for hepatic encephalopathy-related lawsuits., Results: Definitions of a medically impaired driver varied considerably. No state specifically mentioned hepatic encephalopathy or patients with advanced liver disease. Only 6 (12%) of the states had mandatory reporting laws for drivers who have medical impairment, and 25 of the remaining 44 states (57%) provided legal immunity to physicians for reporting such patients. The legal databases did not contain any cases against physicians for failure to warn against driving or diagnose hepatic encephalopathy that resulted in an accident. There were no lawsuits identified against an encephalopathic patient for causing a motor vehicle accident., Conclusions: Only 6 states require physicians to report drivers with medical impairments. Hepatic encephalopathy is not specifically addressed in any state vehicle code. There are no completed lawsuits against physicians or patients for motor vehicle accidents associated with driving impairment from hepatic encephalopathy. In the absence of definitive laws, the onus of responsibility for identifying potentially hazardous drivers might still lie with the physician; physicians should carefully evaluate patients for driving abilities., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Few epidemiologic investigations characterize inflammatory bowel disease (IBD) in non-Caucasian children. Our study compared IBD characteristics between African Americans and non-African Americans enrolled in a multicenter pediatric IBD registry with endoscopic- and pathology-based diagnosis., Methods: The study retrieved data entered from January 2000 to October 2003 on children 1 to 17 years old, inclusive, followed by a consortium of academic and community US pediatric gastroenterology practices. Analyses examined racial/ethnic differences by comparing the proportions of African Americans and non-African Americans in the following categories: each diagnostic disease classification (any IBD, Crohn's disease, ulcerative colitis, indeterminate colitis); age group (<6 y, 6-12 y, or >12 y) at diagnosis or symptom onset; presence of extraintestinal manifestations, Z-scores for height and weight, immunomodulatory therapy, anatomic disease location, and abnormal hemoglobin, albumin, or sedimentation rate at diagnosis., Results: A total of 1406 patients had complete data, 138 (10%) of whom were African American. African Americans more often were older than 12 years of age at diagnosis (52% vs 37%; odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.28-2.59) and symptom onset (46% vs 30%; OR, 1.99; 95% CI, 1.40-2.84); had Crohn's disease (78% vs 59%; OR, 2.36; 95% CI, 1.56-3.58); and had a low hemoglobin level at diagnosis (39% vs 17%; OR, 3.15; 95% CI, 1.92-5.17)., Conclusions: IBD in African American children and adolescents presents more commonly with Crohn's disease and at older ages compared with non-African Americans. Racial/ethnic differences in the epidemiology of IBD, particularly Crohn's disease, among American youths require further investigation.

Background: The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis., Methods: We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient., Results: In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P < 0.001). The 6-17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients., Conclusions: The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.

Objective: The study objective was to investigate responsiveness according to whether patients satisfy eligibility criteria from randomized controlled trials of tumor necrosis factor (TNF) antagonists in a multicentered US cohort., Methods: Biologic-naive patients with rheumatoid arthritis who were prescribed TNF antagonists (n=465) in the Consortium of Rheumatology Researchers of North America registry were included. Patients were stratified by whether they met eligibility criteria from 3 major TNF antagonist trials. Two cohorts were examined: Cohort A (n=336) included patients with complete American College of Rheumatology response criteria except acute phase reactants, and cohort B (n=129) included patients with complete response criteria. Study outcomes included modified American College of Rheumatology 20% and 50% improvement responses (cohort A) and standard American College of Rheumatology improvement (cohort B)., Results: A minority of patients (5.4%-19.4%) prescribed TNF antagonists met trial eligibility criteria and predominantly had high disease activity (78.5%-100%). For patients who met eligibility criteria in cohort A, rates of 20% improvement (52.3%-63.6%) and 50% improvement (30.8%-45.5%) were achieved. Among patients failing to meet eligibility criteria, rates of 20% improvement (16.2%-20.4%) and 50% improvement (8.9%-10.8%) were consistently inferior (P<.05 all comparisons). For cohort B, similar differences were observed., Conclusion: This multicentered US cohort study demonstrates that the majority of patients receiving TNF antagonists would not meet trial eligibility criteria and achieve lower clinical responses. These findings highlight the tradeoff between defining treatment responsive populations and achieving results that can be generalized for broader patient populations.

Abnormal cytokine production by T-helper 1 (Th1)/T-helper 2 (Th2) lymphocytes has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined Th1/Th2 cytokine status in pediatric IBD patients, and results have been inconsistent. We used flow cytometric detection of intracellular IFN-gamma/IL-4 cytokine production to investigate CD4+, Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn's disease (CD) (n = 23) and matched healthy controls (n = 49). Th1 cytokine levels were lower in CD patients compared with controls (p = 0.006) and strongly correlated with levels of albumin and hematocrit (r = 0.51, p = 0.007 and r = 0.35, p = 0.052, respectively). An age-dependent increase in Th1 cells was observed (p < 0.0005); however, no correlation was found between age, clinical end points, %CD4+, or Th2 cell numbers. In conclusion, the Th1 cytokine levels in blood are lower in early onset CD patients than in healthy children and are directly associated with disease-related clinical parameters. In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in intestinal mucosa and peripheral blood.

Background: Whether secondary prevention of atherosclerosis is performed as frequently after cerebrovascular events (stroke or transient ischemic attack) as after cardiac events (myocardial infarction or angina) is unknown., Methods: We compared the receipt of six secondary preventive care processes among 943 persons with a prior cardiac event to that among 523 persons with a prior cerebrovascular event using a representative sample of the US population., Results: The cardiac event group had higher rates for three care processes: antithrombotic medication use in the past year (83-77%, p = 0.01), ever advised to exercise more (66-52%, p < 0.001), and ever advised to eat fewer high-fat or high-cholesterol foods (70-54%, p < 0.001)., Conclusions: Compared to the cardiac event group, the quality of care of the cerebrovascular event group is lower and should be improved.

Objective: To determine the characteristics of inflammatory bowel disease (IBD) in young patients., Study Design: Uniform data were collected from a cohort of patients with IBD who were enrolled from January 2000 to November 2002 at six pediatric centers (Pediatric IBD Consortium)., Results: Of 1370 children in the registry, the mean age at IBD diagnosis was 10.3 +/- 4.4 years; 54% were male, and 86% were white. Diagnosis was confirmed in 87 (6.1%) under 3 years of age, 211 (15.4%) before 6 years, 654 (47.7%) at 6 to 12 years, and 505 (36.9%) at 13 to 17 years. More than 63% of children younger than 8 years of age had isolated colonic disease, whether Crohn disease, ulcerative colitis (UC), or indeterminate colitis. Conversely, only 35% of those 8 years of age or older had isolated colonic disease ( P < .0001). Overall, 29% had one or more family members with IBD. The subgroup of children younger than 3 years of age with UC had the highest prevalence of first-degree relatives with IBD (44%)., Conclusions: This demographically diverse pediatric IBD cohort revealed age-related variation in the distribution of IBD phenotype, with a high prevalence of isolated colonic disease in young children. Positive family history was especially common in young patients with UC.

Objectives: The objectives of this study were to evaluate the safety, pharmacokinetics, and immunogenicity of CDP571 in pediatric patients with Crohn's disease., Methods: A single dose of CDP571, 10 mg/kg, was administered by infusion to pediatric patients (aged 6-17 years) with Crohn's disease in a 12-week open-label study. Adverse events were monitored during infusion and throughout the study. Plasma concentrations of CDP571 and standard clinical and laboratory values were assessed. Changes in disease activity were monitored using the Pediatric Crohn's Disease Activity Index (PCDAI)., Results: Twenty patients were enrolled and stratified by age: 6 to 13 (n = 9) and 14 to 17 years (n = 11). Fourteen patients experienced adverse events, which were mainly mild or moderate in intensity. The plasma concentration profile was consistent with a half-life of approximately 2 weeks. At Week 4, 4 patients in the 6- to 13-year-old group and 2 patients in the 14- to 17-year-old group had detectable anti-CDP571 antibodies. By Week 2, 7 patients in the 6- to 13-year-old group and 6 patients in the 14- to 17-year-old group had responded to treatment (reduction in PCDAI score >10 points)., Conclusion: In conclusion, CDP571 was well tolerated among pediatric patients with Crohn's disease.