Practice Update: Conference Series - EULAR Congress 2017

He said, “Our research findings help explain the higher prevalence of cardio- vascular events observed in patients with chronic immune-mediated inflammatory disease than in the general population.” He continued, “At this stage, our results are significant in better understanding the disease process. They could also carry clinical implications, however, since some of the associated biological pathways are targeted by current therapies for chronic immune-mediated inflammatory disease.” He added, “Gaining a better under- standing of genetic mechanisms underlying cardiovascular disease risk in these patients could be fundamental to developing more efficient preventive and treatment strategies.”

patterns significantly associated with car- diovascular disease risk in these diseases. Two of these genetic patterns showed a highly significant association with car- diovascular disease risk in rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus. Functional analysis of these two genetic patterns revealed their significant enrich- ment in key pathways related to the etiology of rheumatic diseases such as TNFα (FDR <0.05) and IFNγ (FDR < 0.05) cytokine pathways. Dr Julià Cano said that the results rep- resented an important step toward characterising the genetic basis of cardiovascular disease risk in chronic immune-mediated inflammatory disease.

levels were <0.032 μg/mL, the lower limit of quantification of the assay, in 13 of 14 infant blood samples at birth. Only one infant harboured a minimal certolizumab level of 0.042 μg/mL at birth (infant/mother plasma ratio 0.09%). None of the infants harboured quantifiable levels at weeks 4 and 8. Only three of 15 umbilical cord blood sam- ples taken at birth harboured quantifiable certolizumab levels (maximum 0.048 μg/ mL). No anti-certolizumab antibodies were detected in mothers, umbilical cords or infants. Infants of certolizumab-exposed mothers demonstrated safety consistent with that of unexposed similar-age infants. Active transfer of an anti-TNF drug across the placenta involves binding of its frag- ment crystallisable region to the neonatal fragment crystallisable receptor, which in turn may result in adverse foetal or neo- natal effects. than 8500 genome-wide-significant asso- ciations. Cross-phenotype associations are genetic loci that appear to harbour var- iants associated with multiple, sometimes seemingly distinct traits. Cross-phenotype associations have been identified in several disease areas including protein tyrosine phosphatase nonreceptor type 22 (PTPN22) for immune-related disor- ders such as rheumatoid arthritis, Crohn’s disease, systemic lupus erythematosus and type 1 diabetes. The increase in cardiovascular events in patients with chronic immune-mediated inflammatory diseases is explained by a combination of accelerated atheroscle- rosis and endothelial dysfunction, with inflammation providing the central link. Seventeen genetic loci previously identified as being associated with cardiovascular disease risk in the general population were found to be significantly associated with cardiovascular disease risk among the chronic patient groups with immune-medi- ated inflammatory disease (P < 0.05). Of these, four of the loci were found to exert significantly different genetic effects across these diseases (P < 0.05). In addition, six genetic loci linked to chronic immune-medi- ated inflammatory disease risk were found to be associated with an increase in cardio- vascular risk, for example, the risk gene for rheumatoid arthritis CFLAR-CASP8. The cross-phenotype genome-wide meta-analysis identified a total of 10 genetic

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Certolizumab concentration was measured using a sensitive, certolizumab-specific electrochemiluminescence immunoassay, with a lower limit of quantification of 0.032 μg/mL. This assay is 10 timesmore sensitive than the assay used in prior certolizumab pharmacokinetic studies. Maternal certolizumab plasma levels at deliverywerewithin the expected therapeu- tic range (median 24.4 [5.0–49.4] μg/mL). Dr Mariette concluded, “Results of this study support continuation of certoli- zumab treatment during pregnancy when necessary by providing robust information for women who need to control their dis- ease during pregnancy.” He cautioned, “Risks of typical adverse effects associated with anti-TNF treatment, such as infection or an immune reaction, which could affect the outcome of the pregnancy will continue, however.”

In contrast to other anti-TNFs, certoli- zumab lacks this fragment crystallisable region. Ex vivo studies using a human pla- cental transfer model have shown that this unique structure of certolizumab limits its transfer through the placenta to the fetus. The Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia from the Mother to the Infant Via the Placenta (CRIB) was a pharmacokinetic study of pregnant women (≥30 weeks gestation) who received a maintenance dose of certolizumab for an approved indication. The last dose of certolizumab was within 35 days of delivery. Sixteen of 21 certolizumab-treated preg- nant women screened entered the study. Blood samples were collected from the mothers, umbilical cords and infants at delivery, and from infants again 4 and 8 weeks post delivery.

EULAR CONGRESS 2017 • PRACTICEUPDATE CONFERENCE SERIES 17