PreCARA: Preconception Counselling in Active Rheumatoid Artritis and other chronic inflammatory arthritides;
Preconception counselling for women with rheumatoid arthritis (RA) or another chronic inflammatory arthritis and a pregnancy wish, which is evaluated in a prospective observational study monitoring pregnancy, delivery, postpartum period of the mother, and (growth) parameters of the child.

Several rheumatic diseases involve chronic inflammation of one or more joints.
The most common of these is Rheumatoid Arthritis (RA). Other examples are
juvenile idiopathic arthritis, spondylarthritides, and psoriatic arthritis. In
essence these autoimmune diseases are all systematically active and can affect
a variety of organs.
Pregnancy is a very particular condition that can spontaneously reduce the
activity of RA. This phenomenon had been investigated in the PARA-study
(Pregnancy-induced Amelioration of Rheumatoid Arthritis study). This nationwide
prospective cohort study has resulted in some new findings until now. A
specific observation was that one out of five patients (20%) was visited
preconceptionally but stopped attempts to become pregnant because of severe
disease activity after altering medication. These women had to postpone or gave
up their pregnancy wish, due to limited treatment options at the time
compatible with pregnancy. Also a lower fecundity as shown in previous studies
accounts for smaller families of RA patients. Time to pregnancy (TTP) is longer
in RA patients, compared to the general population. This prolonged TTP in RA
is, among others, related to higher disease activity, and preconceptional use
of NSAID*s and prednisone (>7.5 mg daily). Reductions in fertility rate have
been shown in other chronic inflammatory arthritides as well.
In the last decade new treatment options for chronic inflammatory arthritides,
the so-called biologicals, have become available. During pregnancy the most
experience has been gained with anti-TNF alpha (anti tumour necrosis factor
alfa) therapy. In the USA, it has been approved for use during pregnancy as a
FDA (Food and Drug Administration) class B (e.g. Animal studies have revealed
no evidence of harm to the fetus, however, there are no adequate and
well-controlled studies in pregnant women, or, animal studies have shown an
adverse effect, but adequate and well-controlled studies in pregnant women have
failed to demonstrate a risk to the foetus in any trimester). Registry studies
show that anti-TNFα use seems to be safe during pregnancy in humans also.
Furthermore, anti-TNF alfa therapy has been used intentionally
preconceptionally to improve the chance of pregnancies in women with recurrent
spontaneous abortions. However, some case-reports have been published with
adverse pregnancy outcomes, although it is presumed that these adverse outcomes
are no different than in other RA patients. Since no randomized controlled
trials can be done during pregnancy, circumstantial evidence has led to
decision making in daily practice. In case of high disease activity use of
anti-TNFα to control disease activity outweighs the risk of potential harm of
the foetus. It should nevertheless be taken into account that placental
transfer of biologicals from mother to fetus starts at the beginning of the
second trimester and increases until term when maternal and fetal serum levels
are equal or even higher in cord serum. For this reason use of biologicals is
discouraged after the first trimester. In some cases a biological is continued
up till week 30 of gestation because the most markedly increase in placental
transfer takes place after this period. The biological Certolizumab forms an
exception, as it was recently found that this hardly crosses the placental
barrier at all
In the ErasmusMC a protocol was developed to standardize care for patients with
RA or another chronic inflammatory arthritis. This protocol will be evaluated
in the PreCARA study. This study is a continuation of the previous PARA study,
but focuses on a broader group of patients, namely all patients with chronic
inflammatory arthritis who want to become pregnant. We aim to provide national
guidelines for rheumatologists dealing with patients with these conditions,
based on the findings of PreCARA study.

In the present study we will evaluate the standardized care protocol developed
in our outpatient clinic, intended to guide counselling for medication use
prior to pregnancy. This protocol guides treatment decisions based on disease
activity, including prescription of anti-TNF therapy. Disease activity,
fertility, pregnancy outcome and development of the children will be monitored
frequently.

Primary objective:
To evaluate the number of pregnancies in women with RA or another chronic
inflammatory arthritis and a pregnancy wish, by evaluating a recently
implemented protocol in the department of rheumatology at the ErasmusMC
intended for adequate preconceptional counselling by rheumatologists and
gynaecologists.
This will eventually lead to the development of national guidelines for
preconceptional advice in women with chronic inflammatory arthritis and a
pregnancy wish.

Secondary objective:
To prospectively observe pregnancy outcome from mother and child, especially if
conceived under anti-TNFα treatment and prospectively observe immunological,
pharmacological and (social and physical) health issues of the mother and child
before, during and after pregnancy.

Study design: Prospective observational study.

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The treatment decision is made by the consulting
rheumatologist and will be guided by standard health care considerations. Women
are free to consent or refuse the offered treatment proposal. Because of the
scarce data on use of biologicals in the (pre)conception period, they are asked
to give their informed consent in case of use of anti-TNFα treatment.

The burden of regular care:
For rheumatic diseases
1. Consultation, and physical examination at inclusion and subsequently at
every visit (each 3 months) by rheumatologist.
2. Consultation gynaecologist, and 'zwangerwijzer' spreekuur
3. Consultation obstetrician
4. Consultation clinical geneticist (if necessary)
5. Blood samples each 3 months for monitoring disease activity and treatment
toleration

The extra burden resulting from the participation in this study will include:
1. Filling out questionnaires at inclusion and subsequently at every visit
(each 3 months) at rheumatology department
2. Extra blood samples each 3 months (besides regular blood draw, same needle
prick)
3. Complete growth-curves of the child (by parents)