Practice Update: Conference Series

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.

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.

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.”

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

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.

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.”

EULAR CONGRESS 2017 • PRACTICEUPDATE CONFERENCE SERIES