Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients

doi:10.1016/j.jbspin.2015.07.004

Joint Bone Spine

Volume 83, Issue 3, May 2016, Pages 341-343

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Abstract

Objective

Due to reduction of immune-suppressive drugs, patients with rheumatic diseases can experience an increase in disease activity during pregnancy. In such cases, TNF-inhibitors may be prescribed. However, monoclonal antibodies with the Fc moiety are actively transported across the placenta, resulting in therapeutic drug levels in the newborn. As certolizumab (CZP) lacks the Fc moiety, it may bear a lower risk for the child.

Method

We report a case series of thirteen patients (5 with rheumatoid arthritis and 8 with spondyloarthritis) treated with CZP during late pregnancy to control disease activity.

Result

CZP measured in cord blood of eleven infants ranged between undetectable levels and 1 μg/mL whereas the median CZP level of maternal plasma was 32.97 μg/mL. Three women developed an infection during the third trimester, of whom one had a severe infection and one had an infection that resulted in a pre-term delivery. During the postpartum period, 6 patients remained on CZP while breastfeeding. CZP levels in the breast milk of two breastfeeding patients were undetectable.

Conclusion

The lack of the active transplacental transfer of CZP gives the possibility to treat inflammatory arthritis during late gestation without potential harm to the newborn. However, in pregnant women treated with TNF-inhibitors and prednisone, attention should be given to the increased susceptibility to infections, which might cause prematurity. CZP treatment can be continued while breastfeeding.

Introduction

About 50% of the patients with rheumatoid arthritis (RA) and 60% of the patients with spondyloarthritis (SpA) experience active disease during pregnancy, mainly triggered by a reduction of antirheumatic drugs before conception [1], [2], [3]. It is often ignored that active disease during pregnancy is associated with disease progression and with reduced birth weight [4]. On the other hand, the use of prednisone to control disease activity during pregnancy comprises the risk of prematurity [4]. Thus, treatment during pregnancy has to be adapted based on a risk-benefit analysis to prevent disease damage and to allow successful pregnancy. In this context, it is important to note that the use of TNF-inhibitors during pregnancy has not led to adverse pregnancy outcomes [5].

In our outpatient clinic, we advise our patients to plan their pregnancy in inactive disease and to continue TNF-inhibitors until pregnancy is recognized. Furthermore, we inform them that TNF-inhibitors may be restarted during pregnancy, if warranted by a disease relapse. We also discuss the lack of long-term data regarding the health of infants whose mothers were exposed to TNF-blocking agents during pregnancy. Caution has to be taken regarding vaccination of infants in case of an intrauterine exposure to complete monoclonal antibodies against TNF during late pregnancy: therapeutic levels of the TNF-inhibitors in infants may lead to fatal problems if live vaccines, like BCG are given [6].

In contrast to complete monoclonal antibodies against TNF, certolizumab (CZP) lacks the Fc moiety. This modification prevents its binding to placental Fc-receptors and the active transplacental transport to the fetus [7]. Based on this consideration, CZP is the preferred anti-TNF agent to treat active RA and SpA during late pregnancy.

Section snippets

Case series

We report thirteen patients (5 RA, 8 SpA), who were treated with CZP during pregnancy between 2010 and 2013, using 200 mg CZP every 2 weeks. CZP treatment was based on a risk-benefit analysis, and informed and shared decision making was achieved with all thirteen patients. In 2 RA patients and 1 SpA patients, CZP treatment had been continued from the pre-conception period throughout gestation, whereas in all other cases, an exacerbation of the disease during pregnancy indicated CZP therapy

Discussion

In many patients suffering from RA or SpA, a state of disease remission can be achieved if TNF-inhibitors are used. Unfortunately, a stable phase of inactive disease is often lost by a reduction in medication prior to a planned pregnancy. Systematic reviews about the safety of TNF-inhibitors during pregnancy are reassuring. Nevertheless, the placental transfer of IgG1 TNF-inhibitors and its effect on the neonatal immune system prompt us to stop TNF-inhibitors at the time of a positive pregnancy

Conclusion

From our case series of patients treated with CZP during pregnancy, we conclude that a good outcome is seen in the majority of our patients. The minimal transplacental transfer of CZP gives the possibility to treat chronic inflammatory arthritis during the late phase of pregnancy without taking the risk of reaching potentially harmful levels in the newborn. In pregnant women treated with TNF-inhibitors and prednisone, attention should be given to the increased susceptibility to infections,

Disclosure of interest

The authors declare that they have no competing interest.

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Concise reportCertolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients

Abstract

Objective

Method

Result

Conclusion

Introduction

Section snippets

Case series

Discussion

Conclusion

Disclosure of interest

J Crohn's Colitis

Clin Gastroenterol Hepatol

Curr Opin Pharmacol

Am J Med

Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study

Arthritis Rheum

A prospective clinical study of the effect of pregnancy on rheumatoid arthritis and ankylosing spondylitis

Arthritis Rheum

Concise report
Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients