Preclinical Serological Signatures are Associated With Complicated Crohn's Disease Phenotype at Diagnosis.

BACKGROUND: At diagnosis, up to one-third of patients with Crohn's disease (CD) have a complicated phenotype with stricturing (B2) or penetrating (B3) behavior or require early surgery. We evaluated protein biomarkers and antimicrobial antibodies in serum archived years before CD diagnosis to assess whether complicated diagnoses were associated with a specific serological signature. METHODS: Prediagnosis serum was obtained from 201 patients with CD and 201 healthy controls. Samples were evaluated with a comprehensive panel of 1129 proteomic markers (SomaLogic) and antimicrobial antibodies. CD diagnosis and complications were defined by the International Classification of Diseases-Ninth Revision and Current Procedural Terminology codes. Cox regression models were utilized to assess the association between markers and the subsequent risk of being diagnosed with complicated CD. In addition, biological pathway and network analyses were performed. RESULTS: Forty-seven CD subjects (24%) had a B2 (n = 36) or B3 (n = 9) phenotype or CD-related surgery (n = 2) at diagnosis. Subjects presenting with complicated CD at diagnosis had higher levels of antimicrobial antibodies six years before diagnosis as compared with those diagnosed with noncomplicated CD. Twenty-two protein biomarkers (reflecting inflammatory, fibrosis, and tissue protection markers) were found to be associated with complicated CD. Pathway analysis of the altered protein biomarkers identified higher activation of the innate immune system and complement or coagulation cascades up to six years before diagnosis in complicated CD. CONCLUSIONS: Proteins and antimicrobial antibodies associated with dysregulated innate immunity, excessive adaptive response to microbial antigens, and fibrosis precede and predict a complicated phenotype at the time of diagnosis in CD patients.

Maintenance Golimumab Treatment in Pediatric UC Patients With Moderately to Severely Active UC: PURSUIT PEDS PK Long-Term Study Results.

Background: Long-term safety, pharmacokinetics, and efficacy of open-label golimumab therapy in children with moderate-severe ulcerative colitis were evaluated. Methods: Week-6 golimumab responders (Mayo score decrease of ≥30% and ≥3 points from baseline, rectal bleeding subscore of 0/1 or ≥1 decrease from baseline) entered the long-term extension at week 14 and received maintenance therapy (subcutaneous, q4w). Patients ≥45 kg could receive at-home treatments at week 18. Pharmacokinetic, safety, and efficacy results were summarized through week 126 (2 years). Results: Among 35 enrolled children, 21 (60%) responded at week 6 and 20 entered the long-term extension (median age of 14.5 years and median weight of 46.1 kg). Eleven of 20 patients (55%) completed 2 years of treatment. No anaphylactic or serum sickness-like reactions, opportunistic infections, malignancies, tuberculosis, or deaths occurred. The safety profile of golimumab from weeks 14 through 126 and that observed through week 14 was generally consistent. Median trough golimumab concentrations in evaluable patients were consistent from weeks 14 (1.39, interquartile range 0.67-3.60) through 102 (1.18, 0.78-2.16), but higher at week 110 (4.10, 1.30-4.81). The incidence of antigolimumab antibodies increased from 10% (2/20) at week 30 to 25.0% (5/20) at week 126; 1 patient had neutralizing antibodies. At week 110, 50% (10/20) of patients were in remission (ie, Pediatric Ulcerative Colitis Activity Index <10). Among all enrolled patients, 28.6% (10/35) achieved remission at week 110. Conclusions: Among children with ulcerative colitis who initially responded to golimumab induction and received q4w maintenance treatment in the long-term extension, 50% showed continued clinical benefit through 2 years. No new safety signals were observed.

Bariatric surgery for severely overweight adolescents: concerns and recommendations.

As the prevalence of obesity and obesity-related disease among adolescents in the United States continues to increase, physicians are increasingly faced with the dilemma of determining the best treatment strategies for affected patients. This report offers an approach for the evaluation of adolescent patients' candidacy for bariatric surgery. In addition to anthropometric measurements and comorbidity assessments, a number of unique factors must be critically assessed among overweight youths. In an effort to reduce the risk of adverse medical and psychosocial outcomes and increase compliance and follow-up monitoring after bariatric surgery, principles of adolescent growth and development, the decisional capacity of the patient, family structure, and barriers to adherence must be considered. Consideration for bariatric surgery is generally warranted only when adolescents have experienced failure of 6 months of organized weight loss attempts and have met certain anthropometric, medical, and psychologic criteria. Adolescent candidates for bariatric surgery should be very severely obese (defined by the World Health Organization as a body mass index of > or =40), have attained a majority of skeletal maturity (generally > or =13 years of age for girls and > or =15 years of age for boys), and have comorbidities related to obesity that might be remedied with durable weight loss. Potential candidates for bariatric surgery should be referred to centers with multidisciplinary weight management teams that have expertise in meeting the unique needs of overweight adolescents. Surgery should be performed in institutions that are equipped to meet the tertiary care needs of severely obese patients and to collect long-term data on the clinical outcomes of these patients.