Catherine Rowan

Ustekinumab Drug Levels in Maternal and Cord Blood in a Woman With Crohn’s Disease Treated Until 33 Weeks of Gestation

A 35-year old woman with ileocolonic, perianal, and vulval Crohns disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohns disease.

Multifocal Motor Neuropathy Associated with Infliximab

BACKGROUND The anti-tumour necrosis factor [TNF] monoclonal antibody, infliximab, is commonly prescribed in both ulcerative colitis and Crohns disease. Neurological side effects such as optic neuritis are well recognised, although not as frequently seen as hypersensitivity and serious infections. CASE We present a case of peripheral neuropathy in a young man on infliximab therapy for ulcerative colitis. This presented as an asymmetrical and slowly progressive weakness in his right upper limb, severely impacting on function. Investigations confirmed a diagnosis of multifocal motor neuropathy [MMN]. This has been previously described in patients receiving infliximab for rheumatological conditions. The exact mechanism is unclear, but the neuropathy responds well to intravenous immunoglobulin. In our case, infliximab was discontinued. The patient was treated with immunoglobin for 5 days and recovered rapidly. Mercaptopurine was instituted as maintanence therapy, with good effect. CONCLUSION Gastroenterologists prescribing infliximab should be cognisant of both peripheral and central neurological complications, ensuring prompt withdrawal of the offending agent and appropriate alternative treatment.

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence

Background Cytomegalovirus disease in patients with inflammatory bowel disease is frequently the result of viral reactivation. Conversely, primary CMV infection is believed to be uncommon in immunocompetent adults due to high population seroprevalence. Objectives The aim of this study was to examine the frequency and severity of primary cytomegalovirus infection in an adult cohort of IBD patients. Study Design A retrospective review of a prospectively maintained database of 3200 IBD patients attending a single academic centre was performed. Patients with primary CMV infection 2010–13 were identified; clinical, serologic, and virologic parameters were studied in detail. The seroprevalence of CMV in the patient population was also evaluated. Results Eight patients with IBD (UC = 3, IBD-U = 1, CD = 4) presented with primary CMV infection. Patients presented with both gastrointestinal and extraintestinal symptoms. Mean age was 33 years, and median duration of disease was 72 months. All eight patients were receiving a thiopurine immunomodulator. Median duration of IM use was 144 weeks (range 7–720 weeks). All 8 patients required hospitalisation, with 1 ICU admission; the median length of hospital stay was 11 days (range 6–27). Infection resolved in all cases with withdrawal of immunomodulator and/or antiviral therapy. Seroprevalence of IgG to CMV, indicating prior exposure, in a subgroup of IBD patients (n = 80) was 30.5% and increased with age. Conclusion Primary cytomegalovirus infection can cause a severe illness in IBD patients, particularly those receiving immunosuppression. In areas where adult CMV seroprevalence is low, evidence of CMV should be sought in IBD patients presenting with any febrile systemic illness.

Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study

Ustekinumab (USK) is licenced for intravenous induction and subcutaneous (S/C) maintenance in Crohns disease.

P652 Global DNA methylation in inflammatory bowel disease

P651 Identification of new genetic variants related to thiopurineinduced myelotoxicity in inflammatory bowel disease (IBD) patients with normal thiopurines-methyltransferase (TPMT): a genome-wide association study M. Chaparro1 *, A. Gonzalez-Neira2, M. Roman3, G. Pita2, T. Cabaleiro4, D. Herrero2, B. Herraez2, R. Alonso2, C. Taxonera5, P. Lopez-Serrano6, P. Martinez-Montiel7, I. Vera8, F. Bermejo9, A. Lopez-San Roman10, F. Abad-Santos4, J.P. Gisbert1. 1Hospital Universitario de La Princesa, IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Spanish Narional Cancer Research Institute, Madrid, Spain, 3Hospital Universitario de La Princesa and IP, Farmacy Unit, Madrid, Spain, 4Hospital Universitario de La Princesa and IP, Clinical Pharmacology Unit, Madrid, Spain, 5Hospital Clinico San Carlos, Gastroenterology Unit, Madrid, Spain, 6Hospital de Alcorcon, Gastroenterology Unit, Madrid, Spain, 7Hospital Doce de Octubre, Gastroenterology Unit, Madrid, Spain, 8Hospital Puerta de Hierro, Gastroenterology Unit, Madrid, Spain, 9Hospital de Fuenlabrada, Gastroenterology Unit, Madrid, Spain, 10Hospital Ramon y Cajal, Gastroenterology Unit, Madrid, Spain

OUTCOMES OF DOSE ESCALATION WITH ADALIMUMAB (ADA) IN INFLAMMATORY BOWEL DISEASE

Introduction Anti-TNF therapy is highly effective for induction and maintenance of remission in IBD. Subcutaneous agents such as adalimumab are licensed with a fixed dosing schedule irrespective of body weight. Aims/Background We aimed to study the frequency and outcomes of dose escalation with adalimumab and evaluate any relationship to patient body weight. Method A retrospective study of patients who commenced ADA therapy identified from a prospectively maintain database of >3.000 patients with IBD attending a single centre. Results n=143 patients were identified who received adalimumab (ADA) for treatment of inflammatory bowel disease. 25 patients were excluded from the final analysis due to insufficient data. Data on n=118 patients were analysed (99 patients with Crohns Disease, 18 patients with UC, one patient with IBD-U). 62/118 (53%) were male. 43/118 (36%) required dose escalation of ADA from every other week to weekly therapy. The median interval from initiation to dose escalation was 366 days (IQR 153 to 731). The mean body weight at initiation of therapy was similar between both groups (69.5 versus 69.9 kgs, p=ns). The time to dose escalation was not significantly associated with the use of concomitant immunomodulator therapy or with smoking history (current versus ex/never). 28/43 (65%) of patients who received dose escalation responded and 90% remain well on therapy with a median follow up of 1430 days (3.9 years). 15/43 (35%) failed to respond to dose escalation of whom 9 patients underwent surgery and 3 switched to another anti-TNF agent. The mean CRP at dose escalation was higher in the non-responders to to dose escalation than in the responder group (mean CRP 25.2 versus 9.1 mg/dL, p=0.05). Conclusion Dose escalation with ADA is required in over a third of IBD patients but results in a sustained clinical response in the majority of cases. The study results suggests that an ADA dosing strategy based on measurement of ADA levels or inflammatory biomarkers rather than a weight based dosing strategy might help optimise results of therapy.