ROME (FRONTLINE MEDICAL NEWS)Reassuring new data from the German biologics registry RABBIT presented at the European Congress of Rheumatology indicate that exposure to biologic therapies around the time of conception does not increase the risk of malformations or other harmful neonatal consequences.

Observational studies suggest that biologic disease-modifying antirheumatic drugs (DMARDs) are safe to use in patients with rheumatoid arthritis until conception, but questions remain about their influence on birth outcomes, Dr. Anja Strangfeld of the German Rheumatism Research Center, Berlin, and one of the principal investigators for RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), said in a precongress interview. Dr. Strangfeld also noted that questions remained on the course of RA during pregnancy in women who stopped biologic therapy in the first trimester, and how to treat high disease activity, including the use of glucocorticoids.

Her coprincipal investigator, Dr. Angela Zink, also of the German Rheumatism Research Center, presented the new findings during the scientific sessions, which considered 106 pregnancies in 88 women aged 45 years or younger that had occurred between 2001 and the end of 2014. Of these, 42 had occurred in the preceding 3 years.

Among the 38 women who stopped biologics before conception, therapies included rituximab (n = 13), etanercept (n = 12), adalimumab (n = 9), tocilizumab (n = 2), and infliximab (n = 2). Etanercept and adalimumab were the most common therapies among those using biologics at conception, administered in 29 and 11 patients, respectively.

The study identified five spontaneous abortions in 38 pregnancies (13%) in which biologic DMARD infusions or injections were stopped at least 4 weeks before conception and 11 spontaneous abortions among 57 pregnancies (19%) exposed to biologic DMARDs at conception. A total of 11 patients were biologic naive, and no spontaneous abortions were observed. Reassuringly, the rates of spontaneous abortions were within the range of about 15%-20% observed in the general public.

Induced abortions were decided on in 4 of the 106 pregnancies. Three occurred in the 38 women who stopped biologic therapy before conception, including one abortion due to trisomy 21, and the other one was in a women who had been taking biologic DMARD therapy at conception.

The live birth rate was 100% for the biologic-naive women, and 79% for both women who stopped biologic DMARDs before conception and those who had been taking them at conception.

Four congenital defects were reported in live-born children: one anal atresia with urogenital malformation (last adalimumab injection 4 weeks before conception), one congenital nystagmus after preterm birth (last adalimumab injection > 6 months before conception), and one case of spina bifida (last etanercept injection > 9 months before conception). There was also one case of talipes in a child whose mother reported also having talipes and had been taking adalimumab at time of conception.

Although the analysis includes a limited sample of pregnancies, these data confirm previous reports and show no increased risk of major malformations or other harmful consequences in patients exposed to biologic therapy around conception.

“We found that, in patients with long-standing rheumatic disease, remission during pregnancy is rarely reached,” Dr. Zink observed. In fact, “disease activity increased during pregnancy in a considerable proportion of the patients,” she added. This is in contrast to other studies and experience, however, she acknowledged, where disease activity has been shown to reduce during pregnancy.

Of 23 patients who were in already in remission before conception, 10 (43%) remained in remission during their pregnancies. Of the 49 patients who had not been in remission before pregnancy, only seven (14%) went into remission during pregnancy.

Dr. Zink noted that a new German pregnancy registry, RHEKISS , will start recruitment in July 2015 to observe treatment needs from the first desire to conceive or early pregnancy (first trimester) until the child’s second birthday. This register will initially include women with any inflammatory rheumatic disease but will later also include male patients whose partner is pregnant.

In a separate presentation, Dr. John J. Cush of Baylor Research Institute and Baylor University Medical Center in Dallas reported other data on the safety of tumor necrosis factor inhibitors (TNFis) in pregnancy. He presented prospectively collected data on pregnancy outcomes in 78 women with rheumatic disease and 148 women with other inflammatory diseases, such as Crohn’s disease, who were exposed to certolizumab pegol (Cimzia) from the manufacturer UCB Pharma’s global safety database.

He observed that because certolizumab’s structure lacks an Fc region, it was potentially a more favorable anti-TNF therapy to use during pregnancy than etanercept, infliximab, adalimumab, or golimumab because it was thought to be less likely to cross the placental barrier and affect the developing fetus.

“Live births were reported for the majority of pregnancies of women with rheumatic diseases following maternal certolizumab exposure,” Dr. Cush said.

Almost three-quarters (73.1%) of the 78 women with rheumatic disease had a live birth with no congenital malformations. Around 5% of live births were associated with congenital malformations, and the rates of spontaneous and induced abortions were a respective 11.5% and 14.1%.

In the 132 women with nonrheumatic inflammatory diseases, there were 86.6% live births without and 4.4% with congenital abnormalities and 9.1% and 5.3% spontaneous and induced abortions.

For all indications, there were 12 congenital malformations from 254 live births. These included anal fistula, polydactyl left hand, posterior ankyloglossia, renal cyst for which no treatment was needed, pyloric stenosis, club foot, and left-sided vesicoureteral reflux.

Dr. Cush noted that one neonate in a set of premature twins delivered at 26 weeks died due to brain damage and pneumoperitoneum.

Importantly, the data were “encouraging” he said and “suggest that certolizumab exposure in utero, including the first trimester of exposure, does not adversely affect pregnancy outcome.”

The German biologics registry RABBIT is supported by grants from AbbVie, BMS, Celltrion, Hospira, MSD, Pfizer, Roche, and UCB. Dr. Strangfeld reported having no disclosures. Dr. Zink has received speaker fees from AbbVie, BMS, MSD, Pfizer, Sanofi Aventis, Roche and USB. Dr. Cush disclosed receiving research grants from Pfizer, Celgene, CORRONA, Amgen, the National Institutes of Health, Novartis, and UCB.


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