Background:Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor.Objective:To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA).Methods:An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function.Results:Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis.Conclusion:Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression.Trial registration number:NCT00175877

SummaryAn ELISA specific for a wide spectrum of oxidized apo B-100 in OxLDL was developed and applied to blood samples from 27 control subjects, 20 mild chronic renal failure (MCRF) patients, 21 severe chronic renal failure patients on conservative treatment (SCRF) and 56 severe chronic renal failure patients on maintenance hemodialysis (HEMO). Mean levels of OxLDL were 0.59 mg/dl in controls (95% Cl, 0.52-0.66 mg/dl), and were 2.7-fold (p <0.01), 3.1-fold (p <0.001) and 5.4-fold (p <0.001) higher in MCRF, SCRF and HEMO patients, respectively. Levels of von Willebrand factor, a marker of endothelial injury, were 100 percent in controls (95% Cl, 90-110 percent), and were 1.5-fold (p = NS), 1.6-fold (p <0.01) and 2.1-fold (p <0.001) higher in MCRF, SCRF and HEMO patients, respectively. Multiple regression analysis revealed that the extent of renal failure (F = 14; p = 0.0004) accounted for a significant fraction of the variation in OxLDL levels, also after exclusion of patients with evidence of ischemic atherosclerotic disease (F = 21; p = 0.0001). After adjustment for the extent of renal failure, hemodialysis (F = 5.6; p = 0.021) and LDL cholesterol levels (F = 7.1, p = 0.0095) contributed significantly to the variation in OxLDL levels. Whereas the extent of renal failure contributed only marginally to the individual variations in vWF levels (F = 4.1; p = 0.048), these levels correlated significantly with plasma levels of OxLDL (F=26; p=0.0001). In conclusion, atherogenic OxLDL increase progressively during the development of renal failure suggesting that the oxidation of LDL may be associated with endothelial injury and atherogenesis in these patients.

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...

SUMMARYNine ectomycorrhizal fungi bave been studied for their effect on the growth oi Pinus syhestris L. seedlings. Tbe plants were kept growing for six months in root chambers witb a changeable volume. Al! seedlings were cultivated under conditions of low substrate nutrient concentrations and they became strongly infected within a short time. We demonstrated the existence of an important negative correlation between tbe extent of the fungal development and the growth of tbe host plants. In most studies tbis reduced growth is attributed to an energy drain by tbe fungus. Fungi producing large amounts of fungal tissue are more energy consuming than species wbicb only develop a sparse mycelium. However we suggest that also nitrogen acquisition by tbe plants might be altered by the fungus. Certain fungi probably retain a considerable amount of nitrogen for tbeir own growth, thus reducing the amount transported to the host plant. A decreased N transport finally results in a slower growtb. In tbis study the extramatrical mycelium in the rooting substrate was determined by wet oxidation and by nitrogen determination. This component of the fungal biomass showed the biggest variation a.inong the different tnycohiont species. Tbe results are discussed in relation to the culture technique employed.

Results. All measures were correlated significantly: RAPID3 with DAS28 and CDAI (rho > 0.7), higher than erythrocyte sedimentation rate with C-reactive protein level (rho ‫؍‬ 0.47). At 52 weeks, DAS28, CDAI, and RAPID3 low activity/ remission was seen in 30%, 44%, and 42% of CZP-treated patients versus 3%, 7%, and 10% of control patients. Good, moderate, and poor EULAR-DAS28 responses were seen in 30%, 51%, and 19% of CZP-treated patients versus 3%, 28%, and 70% of control patients, and for RAPID3 in 39%, 30%, and 32% of CZP-treated patients versus 8%, 16%, and 76% of control patients. Kappa and weighted kappa values ranged from 0.36 -0.53, indicating fair to moderate agreement. Conclusion. RAPID3, DAS28, and CDAI give similar results to distinguish CZP patients from controls in the RAPID 1 clinical trial. DAS28 is specific for clinical trials; RAPID3 appears pragmatically useful for usual care.