James Rick

Clinical Presentation and Five-Year Therapeutic Management of Very Early-Onset Inflammatory Bowel Disease in a Large North American Cohort

OBJECTIVE To evaluate the presentation, therapeutic management, and long-term outcome of children with very early-onset (VEO) (≤ 5 years of age) inflammatory bowel disease (IBD). STUDY DESIGN Data were obtained from an inception cohort of 1928 children with IBD enrolled in a prospective observational registry at multiple centers in North America. RESULTS One hundred twelve children were ≤ 5 years of age with no child enrolled at <1 year of age. Of those, 42.9% had Crohns disease (CD), 46.4% ulcerative colitis (UC), and 10.7% had IBD-unclassified. Among the children with CD, children 1-5 years of age had more isolated colonic disease (39.6%) compared with 6- to 10-year-olds (25.3%, P = .04), and 11- to 16-year-olds (22.3%, P < .01). The change from a presenting colon-only phenotype to ileocolonic began at 6-10 years. Children 1-5 years of age with CD had milder disease activity (45.8%) at diagnosis compared with the oldest group (28%, P = .01). Five years postdiagnosis, there was no difference in disease activity among the 3 groups. However, compared with the oldest group, a greater proportion of 1- to 5-year-olds with CD were receiving corticosteroids (P < .01) and methotrexate (P < .01), and a greater proportion of 1- to 5-year-olds with UC were receiving mesalamine (P < .0001) and thiopurine immunomodulators (P < .0002). CONCLUSIONS Children with VEO-CD are more likely to have mild disease at diagnosis and present with a colonic phenotype with change to an ileocolonic phenotype noted at 6-10 years of age. Five years after diagnosis, children with VEO-CD and VEO-UC are more likely to have been administered corticosteroids and immunomodulators despite similar disease activity in all age groups. This may suggest development of a more aggressive disease phenotype over time.

Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease

BACKGROUND & AIMS It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohns disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy. METHODS We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohns disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy. RESULTS The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively. CONCLUSIONS In children with Crohns disease, concomitant treatment with an immunomodulator for more than 6 months after starting infliximab therapy increases the chances that patients will remain on infliximab. In boys, methotrexate appears to increase the durability of infliximab therapy compared with thiopurine.

Retrospective cohort study of Methotrexate use in the treatment of pediatric Crohn's disease

Background:Methotrexate (MTX) use as an alternative to thiopurines in the treatment of Crohns disease (CD) in children is increasing. This study was undertaken to assess safety and efficacy of MTX in children with CD. Methods:Patients treated with MTX with a minimum of 1-year follow-up were identified in the Pediatric IBD Collaborative Research Group Registry, a prospective inception cohort study started in 2002. The clinical efficacy and safety of MTX were analyzed retrospectively. Results:Two hundred ninety patients treated with MTX were identified. One hundred seventy-two patients received at least 3 months of MTX without thiopurine or biologicals and had ≥1 year of follow-up. Eighty-one of 172 patients (47%) received MTX as first immunomodulator (IMM), of which 22 (27%) achieved ≥12 months of sustained clinical remission without surgery, thiopurine, biologicals, or corticosteroids. Those receiving MTX as second IMM achieved similar remission rate (35%, P = not significant). Fourteen percent received MTX as first IMM in 2002 and 60% in 2010 (P = 0.005). Disease location did not affect outcomes. MTX doses were equivalent in both groups. Fifteen percent of patients developed an alanine aminotransferase >60 international units/liter and 12% developed a white blood cell <4000 cells per microliter while on MTX. Only 4% of these discontinued MTX completely. A small group of 6 centers, which contributed only about one-third of patients with CD in the registry, contributed nearly two-thirds of the patients receiving MTX (P < 0.001). Conclusions:MTX use as first choice IMM is increasing in pediatric CD. MTX provided sustained clinical remission in nearly one-third of patients with minimal toxicity. There is large center-to-center variability in its use.

Liver Enzyme Elevations Within 3 Months of Diagnosis of Inflammatory Bowel Disease and Likelihood of Liver Disease

Background: Inflammatory bowel disease–associated liver diseases (IBD-LDs) include autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and an overlap syndrome. Prospective unbiased multicenter data regarding the frequency of IBD-LD in patients with pediatric inflammatory bowel disease (IBD) are lacking. We examined early alanine aminotransferase (ALT) and &ggr;-glutamyl transpeptidase (GGT) elevations in children diagnosed as having IBD and assessed the likelihood of IBD-LD. Methods: Data collected from the prospective observational Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry enrolling children of age <16 years within 30 days of diagnosis. AIH, PSC, and overlap syndrome were diagnosed using local institutional criteria. Results: A total of 1569 subjects had liver enzymes available. Of the total, 757 had both ALT and GGT, 800 had ALT only (no GGT), and 12 had GGT only (no ALT). Overall, 29 of 1569 patients (1.8%) had IBD-LD. IBD-LD was diagnosed in 1 of 661 (0.15%) of patients with both ALT and GGT ⩽ 50 IU/L compared with 21 of 42 (50%) of patients with both ALT and GGT > 50 (odds ratio 660, P < 0.0001). Of the 29 patients with IBD-LD, 21 had PSC, 2 had AIH, and 6 had overlap syndrome. IBD-LD was more common in patients with ulcerative colitis and IBD-unclassified (indeterminate colitis) than in those with Crohn disease (4% vs 0.8%, respectively, P < 0.001). Conclusions: Elevation of both ALT and GGT within 90 days after the diagnosis of IBD is associated with a markedly increased likelihood of IBD-LD. Both ALT and GGT levels should be measured in all of the pediatric patients newly diagnosed as having IBD.

P-163 Pulmonary Manifestations At Time of Diagnosis of Crohnʼs Disease: Report of Two Pediatric Cases

BACKGROUND: Inflammatory bowel disease (IBD) is a systemic disorder and extra-intestinal manifestations (EIM) are very common. Although there is mounting evidence showing a relationship between pulmonary involvement and IBD, respiratory tract disease as an EIM continues to be under recognized. Reported pulmonary complications include inflammation of the small and large airways, pulmonary parenchymal disease, serositis, and pulmonary embolism. Involvement can predate the diagnosis, occur at time of diagnosis, or develop later in the disease course. It can also be associated with treatments, infections and auto-immune disorders. We present 2 pediatric patients with Crohn’s disease (CD) and pulmonary manifestations near the time of initial intestinal disease symptoms. The first patient presented with parenchymal disease predating the diagnosis of CD. The second patient sustained a non-traumatic pneumothorax related to pleural blebs around the time of diagnosis. METHODS: Case Report. RESULTS: A 15 year old female presented with cough, fever, and weight loss. Chest computed tomography (CT) showed multiple left lung masses with cystic change. IV antibiotics (ceftriaxone and vancomycin) were given. An infectious etiology was not identified. Spirometry was normal. Her respiratory symptoms and her pulmonary involvement by CT improved, but did not resolve. Over the next 3 weeks, she developed diarrhea, weight loss, vomiting, and worsening abdominal pain. She had a microcytic anemia, elevated ESR and hypoalbuminemia. Upper gastrointestinal series showed jejunal thickening. Gastrointestinal endoscopy showed granulomatous gastritis, duodenitis, active, chronic ileitis, and pan-colitis. She responded well to induction with corticosteroids and maintenance of remission with 6mercaptopurine was achieved. Repeat chest CT showed the lung lesions had resolved. A 15-year old male presented with pleuritic chest pain, weight loss, and poor appetite. Laboratory evaluation demonstrated microcytic anemia and elevated ESR. An incidental small pneumothorax with pleural bleb formation was seen in the left lung base on abdominal CT. Also, there was extensive thickening of the ileum and an adjacent 1.3 cm extraluminal fluid collection. Ciprofloxacin and metronidazole were given. Due to increasing chest pain and fatigue, he was admitted and treated with oxygen. Ileitis was found on gastrointestinal endoscopy and biopsies confirmed acute and chronic inflammation consistent with CD. Induction with corticosteroids improved the clinical situation but mild disease activity remained. Oral budesonide and methotrexate have led to clinical remission. There are no lingering pulmonary symptoms. The pneumothorax and pleural abnormalities resolved on follow up imaging. Spriometry is planned to evaluate for airway disease. CONCLUSIONS: Pulmonary manifestations of CD are infrequently seen in adults and pediatrics, yet there is a growing awareness of the relationship and spectrum of complications. The timing of respiratory disease is variable and can manifest before, after or during the time of diagnosis. These 2 cases highlight the need to consider CD as a potential cause of parenchymal lung disease and pneumothorax even in patients without known IBD. In patients with known IBD, prompt recognition and treatment of pulmonary disease are essential to prevent potential destructive and irreversible pulmonary changes. Figure. No caption available.

831 Prospective Cohort Study of Methotrexate Use in Treatment of Pediatric Crohn Disease

Early Anti-TNFα Therapy Is Superior to Early Immunomodulator Therapy in Newly Diagnosed Children With Crohns Disease Jeffrey S. Hyams, Mi-Ok Kim, Lee Denson, Anne M. Griffiths, Marla Dubinsky, James Markowitz, Robert Baldassano, Wallace Crandall, Joel R. Rosh, Marian D. Pfefferkorn, Anthony R. Otley, Melvin B. Heyman, Neal S. Leleiko, Susan S. Baker, Stephen L. Guthery, Jonathan Evans, David Ziring, Richard Kellermayer, Michael C. Stephens, David R. Mack, Maria Oliva-Hemker, Jonah B. Essers, Ashish S. Patel, Barbara S. Kirschner, Dedrick E. Moulton, Stanley A. Cohen, Chunyan Liu, Subra Kugathasan, Thomas D. Walters