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Background Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF approved in 45 countries for the treatment of rheumatoid arthritis (RA) and/or Crohn's disease (CD); it was recently approved by the EMA for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Analysis of pregnancy data from the UCB Pharma global safety database through 06 March 2012 has been published previously.1 Objectives To provide an updated analysis of pregnancy outcomes in rheumatic patients (pts) after CZP exposure, with a focus on RA, by including new reports and pregnancies that were still ongoing at the time of the last retrospective analysis. Methods The UCB Pharma global safety database, designed to house and report adverse events for UCB Pharma products, was searched for all medically confirmed cases of pregnancy through 28 March 2013. Reported pregnancies included women who became pregnant while participating in a clinical study and spontaneous post-marketing reports. The number of live births, spontaneous miscarriages and elective terminations for neonates exposed to CZP (maternal and paternal exposure) was examined. Congenital abnormalities, neonatal deaths and maternal demographics were also investigated. Results As of 28 March 2013, 309 CZP exposed pregnancies were reported: 285 were maternal exposure, 24 were paternal. For pregnancies with maternal exposure, although the major underlying condition was CD (190/285), RA was the underlying condition for 52 of the 285 women with the remaining 43/285 encompassing other indications, including axSpA and PsA. Pregnancy outcomes were available for 190 of these 285 pregnancies: 42 in women with RA, 124 in women with CD and 24 in women with other rheumatic indications. For the 42 pregnancies in women with RA with known outcomes, whether spontaneously reported or within a clinical trial context, 26 (61.9%) resulted in live birth, 9 (21.4%) in spontaneous miscarriage and 7 (16.7%) in elective termination. The Table presents characteristics for pregnancies in women with RA compared to those for all reported maternal exposure pregnancies. Five congenital anomalies were reported, in four neonates, among all live births with maternal CZP exposure (n=132): vesicoureteric reflux, congenital morbus hirschsprung disease and club foot, right aortic arch with aberrant left subclavian artery, and mild unilateral hydronephrosis on antenatal ultrasound (described as healthy upon birth). None of these events were considered related to CZP by the treating physicians. A single neonatal death was reported after maternal exposure in one of a set of twins delivered before 26 weeks of gestation. Conclusions Updated analysis of pregnancy outcomes after exposure to CZP supports previous reports suggesting no apparent impact of maternal CZP exposure on pregnancy outcomes. Additional prospective data are required to fully evaluate the safety and tolerability of CZP in pregnancy. References Clowse M. Arthritis Rheum 2012; 64(Suppl10):S702 Acknowledgements The authors acknowledge Co...

Background: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. Aim: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. Methods: This was an open‐label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6–9 on a 12‐point scale. Fifty‐six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end‐point was response, defined as a final disease activity index of ≤ 3. Supplementary analyses were also performed. Results: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty‐seven (49%) improved, with a final disease activity index of ≤ 3 or a four‐point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). Conclusions: In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

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In a 3-month prospective study among 203 Austrian outpatients with diarrhea, the role of pathogenic Escherichia coli and the use of the polymerase chain reaction in screening Escherichia coli isolates from clinical stool specimens were evaluated. Enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli combined were identified as the second most frequent cause of diarrhea. Of a total of 85 bacterial pathogens isolated from 80 patients, 15 were pathogenic Escherichia coli, 13 enteroaggregative Escherichia coli and two enterotoxigenic Escherichia coli. Enteropathogenic, enteroinvasive, and enterohemorrhagic Escherichia coli isolates were not detected.