Ludek Hrdlicka

Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease

BACKGROUND AND AIMS Over 10% of Crohns disease (CD) patients annually lose response to infliximab. Infliximab trough levels (TL), concomitant immunosuppressants and endoscopic healing were proposed as predictors of favourable infliximab outcome. We assessed infliximab TL measured after induction therapy as predictors of sustained clinical response. Furthermore, we tried to identify other predictors of long-term benefit of infliximab therapy. METHODS We included CD patients treated with infliximab between October 2007 and March 2010 who responded to 3-dose induction followed by maintenance therapy and in whom blood samples taken at treatment week 14 or 22 were available in blood bank. Sustained response to infliximab was defined as absence of treatment failure due to loss of response or drug intolerance. RESULTS Eighty four patients were included. Sustained response to infliximab was observed in 47 (56%) patients during a median follow-up of 25 months (14-37). Infliximab TL>3μg/ml were associated with a decreased risk of treatment failure (HR 0.34; 95% CI: 0.16-0.75), whereas the presence of antibodies against infliximab and need for corticosteroids increased this risk (HR 4.34; 95% CI: 1.51-12.5 and HR 2.49, 95% CI: 1.08-5.73, respectively). No impact of concomitant thiopurines was observed, although patients receiving thiopurines had higher infliximab TL than those without immunomodulators (5.51 vs. 0.71μg/ml; p=0.01). CONCLUSION During a median follow up of 2 years sustained response to infliximab was observed in slightly more than half of CD patients. Infliximab TL>3μg/ml at the start of maintenance regime were predicative of sustained response to infliximab.

Impact of Anti–Tumor Necrosis Factor Alpha Antibodies Administered to Pregnant Women With Inflammatory Bowel Disease on Long-term Outcome of Exposed Children

Background:Prenatal exposure to anti–tumor necrosis factor &agr; (TNF-&agr;) antibodies seems to be safe for fetal development. Data on long-term outcome of exposed children are missing. Our aim was to assess long-term postnatal development of children exposed to anti–TNF-&agr; during pregnancy. Methods:Consecutive children aged ≥12 months exposed to anti-TNFs prenatally for maternal inflammatory bowel disease in 3 centers in the Czech Republic were enrolled. Data on psychomotor development, infections, antibiotics, vaccination, and allergy were retrospectively obtained from mothers, treating pediatricians, and childrens vaccination cards. Furthermore, standardized laboratory tests on humoral and cellular immunity were performed. Results:Twenty-five children exposed to biologicals were included (median age, 34 mo; range, 14–70 mo). All children had normal growth, and all but 1 had normal psychomotor development. Majority (80%) experienced at least 1 infection (mainly respiratory), and 60% of infants received antibiotics, 32% of those within the first year of life. Vaccination was undertaken according to vaccination protocol to 23 infants (92%). Fifteen children also had tuberculosis vaccination without serious complication. Immunological investigation was performed with 17 children (68%). Cellular immunity was normal in all infants, and 7 children had mild decrease in IgA and/or IgG immunoglobulins without clinical significance. All children had a detectable serologic response to vaccination. Conclusions:Exposure to anti–TNF-&agr; antibodies seems to be safe for growth and psychomotor development of children, although clinical significance of relatively high frequency of infections and antibiotic use among infants remains questionable because of the lack of a control group. Continuous follow-up of exposed children is absolutely warranted.

Pregnancy and newborn outcome of mothers with inflammatory bowel diseases exposed to anti-TNF-α therapy during pregnancy: three-center study

Abstract Objective. Substantial number of women with inflammatory bowel disease (IBD) conceives while on anti-TNF-α therapy. The aim was to assess the safety and efficacy of anti-TNF-α treatment during pregnancy and to analyze relationship of neonatal and maternal anti-TNF-α levels at delivery with gestational age at the last exposure. Material and methods. Women with IBD exposed to anti-TNF-α therapy during pregnancy were included. Data on anti-TNF-α treatment, disease activity, concomitant medication, pregnancy and newborn outcome were recorded. Anti-TNF-α levels from cord blood were assessed by ELISA. Results. Forty-one pregnancies (27 Crohns disease; 14 ulcerative colitis) were exposed to infliximab (IFX; 32) and adalimumab (ADA; 9). Ten (24%) women had active disease at conception and 31 (76%) were in remission with 3 patients experiencing relapse during pregnancy. Anti-TNF-α therapy started prior to and after conception in 32 and 9 women, respectively. There were 34 (83%) live births (median birth weight 3145 g) of which 28 were at-term and 6 preterm deliveries. Five (12%) pregnancies ended in spontaneous and two in therapeutic abortion. No congenital malformations except for one case of hip dysplasia were observed. Similarly, no serious perinatal complication occurred. IFX cord levels measured in 11 children positively correlated with gestational week at the last drug administration and maternal levels at delivery, while no such correlation was found in case of ADA. Conclusions. The results confirm that anti-TNFs are effective and safe during pregnancy. A positive correlation between IFX cord levels and gestational week of last exposure as well as maternal serum levels was observed.

P360 Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease: A single cohort study

P360 Infliximab trough levels may predict sustained response to infliximab in patients with Crohn’s disease: A single cohort study M. Bortlik1 *, D. Duricova2, K. Malickova3, A. Komarek4, N. Machkova5, E. Bouzkova6, L. Hrdlicka6, M. Lukas7. 1Iscare Lighthouse, IBD Centre, Prague, Czech Republic, 2Charles University, IBD Clinical and Research Centre, Prague, Czech Republic, 3Charles University, Institute of Clinical Biochemistry and Laboratory Diagnostics, Prague, Czech Republic, 4Faculty of Mathematics and Physics, Charles University, Department of Probability and Mathematical Statistics, Prague, Czech Republic, 5IBD Clinical And Research Center Iscare, Gastroenterology, Prague, Czech Republic, 6Charles University, IBD Clinical and Research Centre, Iscare, Prague, Czech Republic, 7Clinical Centre Isacre Lighthouse, IBD Clinical and Research Centre, Prague, Czech Republic

Tu1141 Mucosal Healing of Small Bowel Crohn's Disease After Anti-TNFα Therapy Assessed by Capsule Endoscopy

BACKGROUND:Inflammatory bowel disease (IBD) patients have an increased risk of osteoporosis related fractures. Necessity of bone density measurement in IBD patients is not clearly defined, however, the risk of fracture increases among them. Fracture Risk Assessment Tool (FRAX) score computes the 10-years probability of the major osteoporotic fractures and particularly hip fracture. Clinical FRAX (c-FRAX) does not include the bone mineral density (BMD) measurement. We aimed to compare the value the c-FRAX to FRAX enhanced with dual x-ray absorptiometry (DEXA) (bmd-FRAX) in IBD patients. METHODS:169 consecutive IBD patients (128 Crohns disease (CD) and 41 ulcerative colitis (UC); female/male: 88/81) were included into the study. Mean age of the patients was 35.9±11.7 years, 7.6% of them was postmenopausal women. FRAX-scores were calculated with the online tool using a Hungarian algorithm. Bone mineral density measurements were performed by DEXA. Calculations were performed using SPSS statistics 15.0 software. RESULTS:In patients under 40 the c-FRAX score regardingmajor osteoporotic fracture riskwas significantly higher compared to bmd-FRAX (1,9±1,1 vs. 1,4±0,8, p,0,01). The same difference was observed computing the probability of hip fractures (c-FRAX: 0,4±0,7 vs. bmd-FRAX: 0,3±0,5; p ,0,05). In a subgroup analysis the fracture risks have not differed in CD vs. UC patients. Major fracture risk c-FRAX and bmd-FRAX were 3,0±3,4% es 2,4±2,7% in CD and 3.4±3.4% and 2.5±2.4% in UC patients (non-significant (NS)). Clinical FRAX and bmd-FRAX showing hip fracture risk were 0.8±1.5% and 0.6±1.4% in CD and 0.8±1.3% and 0.4±0.7% in UC, respectively (NS). We did not observe any correlation between FRAX scores and calcium intake, physical activity, severity, extentand duration of the disease. Subgroup analysis regarding steroid use and body mass index has not been performed due to the FRAX system included in these parameters. CONCLUSION:Guidelines regarding IBD associated osteoporosis advise to perform the DEXA measurements in patients with some special risk factors for bone loss. In our study the fracture risk according to FRAX scores completed with DEXA were lower than clinical FRAX especially in patients younger than 40 years. Our results suggest that DEXA enhanced FRAX may have an advantageous role in preventing over medicating young IBD patients.

P492 Impact of anti-TNFa therapy of inflammatory bowel disease during pregnancy on long-term outcome of exposed children

Methods:Aquestionnaire including 6 main questions and a basic section with regard to personal information was sent to all gastroenterologists in Switzerland. Results: The vast majority of all Swiss GI specialists (90%) use a thiopurine as the first step up strategy after steroids and not anti-TNF(7.5%) or combo-therapy (2.5%) up front. While 41.2% of all Swiss gastroenterologists state to have no specific preference for any TNF-inhibitor, IFX is the favourite anti-TNF agent in 47.1% (ADA 10.9% and CTZ 0.8%). IFX is even significantly more preferred in those seeing less than 30 IBD patients per year (57.4%; >30. Pat 36.2%, p = 0.02). To address LOR the most preferred strategy is shortening the interval of anti-TNF administration in 49.5% of doctors (mean 5.4 on a scale from 1 to 6; lowest and highest agreement, respectively), followed by increasing the dose (5.0), switching the TNF-inhibitor (4.9), add a thiopurine (3.9), initiate a full re-induction (3.6), add prednisone (3.5), refer to surgery (3.5) and add methotrexate (2.9). In case of prolonged remission on combo therapy Swiss gastroenterologists stop one drug after a mean of 15.7 month (with a fairly wide range from 6 to 48 month). The thiopurine is stopped first in most cases (50.8%; TNF-inhibitor first 40%, only 4.2% continue both therapies, stop both at the same time 1.7%, other 3.3%). Conclusions: In the case of LOR dose intensification prior to switching of the TNF-inhibitors is most often used among Swiss gastroenterologists. Regarding step-up and de-escalation strategies GI specialists in Switzerland still mainly apply a conventional step-up with thiopurines. In the case of prolonged remission, stopping the immunosuppressant first is preferred.