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A patient’s wish: anakinra in pregnancy
  1. C T Berger1,
  2. M Recher1,
  3. U Steiner1,
  4. T M Hauser1,2
  1. 1
    Immunology Clinic, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland
  2. 2
    Immunologie-Zentrum Zürich, Zurich, Switzerland
  1. Correspondence to Dr T Hauser, Immunologie-Zentrum Zürich, Walchestrasse 11, 8006 Zurich, Switzerland; hauser{at}immunologie-zentrum.ch

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Patients with adult-onset Still’s disease (AOSD) are at increased risk for adverse outcomes of pregnancy. An increased rate of preterm birth, intrauterine growth retardation and a possible influence of disease activity on pregnancy outcome have been reported.1 Interleukin 1 (IL1) is thought to have a key role in the pathogenesis of AOSD. Interestingly, it has also been related to an increased risk of preterm birth in animal models.2 3 An increasing number of reports on treatment of refractory AOSD with IL1 receptor antagonist (anakinra) emphasise its dramatic therapeutic effect and the rarity of its adverse events.4 5 However, its effects in pregnancy are not well known. Here we report successful continuous treatment of AOSD during pregnancy and breastfeeding.

A 33-year-old woman with AOSD currently treated with recombinant IL1 receptor antagonist (IL1ra, anakinra) expressed the wish to become pregnant. Her disease course was refractory to treatment with prednisone alone or in combination with azathioprine or etanercept (fig 1). In July 2006 during a severe flare while receiving prednisone, anakinra was initiated at 100 mg/day. The patient became rapidly asymptomatic and prednisone was tapered and subsequently stopped in December 2006.

Figure 1

C-reactive protein (squares) and ferritin (circles) serum concentrations were monitored at the indicated time points. The black bar shows the duration of pregnancy. *Highlights the increase in C-reactive protein after a single missed injection of anakinra. The respective start of different therapeutic regimens is depicted by arrows as follows: (1) prednisone (initial dose 1 mg/kg/day); (2) prednisone + azathioprine (2 mg/kg/day); (3) prednisone + etanercept (2×25 mg subcutaneously/week); (4) anakinra subcutaneously 100 mg/day (first 6 months combined with tapered prednisone).

Despite extensive warning about the lack of knowledge of the effects of IL1ra on fetal development, she decided to continue anakinra during pregnancy. Two months after discontinuation of contraception, pregnancy was diagnosed. The adjusted risk for trisomy-21 based on age, β-HCG, PAPP-A and length of the nuchal fold was 1:8100. α-Fetoprotein was normal. Ultrasound repeatedly demonstrated normal growth and no evidence of malformation. Doppler analysis of the uterine artery was always normal. She remained free of signs of AOSD with the exception of one short flare after having missed a single dose of anakinra (fig 1). In April 2008, she gave spontaneous birth to a girl at 40+5 weeks of gestation: weight: 2700 g (5th centile), length 46 cm, APGAR Score 7/8/9, umbilical cord arterial pH 7.17. Birth was complicated by retention of the placenta requiring manual abruption. There were no pathological findings on thorough paediatric examination at discharge.

Postpartum, the mother decided to breastfeed despite continuation of treatment with anakinra. The child showed steady growth (10th to 25th centile) and inconspicuous psychomotor development during follow-up. The patient remained free of signs of AOSD until 4 months after delivery when a flare occurred during continuous monotherapy with anakinra.

To our knowledge, this is the first report of treatment of AOSD with anakinra during pregnancy and breastfeeding. Treatment with anakinra has not been recommended during pregnancy.6 No teratogenic effects were demonstrated in animal studies of anakinra,6 but nidation was thought to be compromised.7 Of note, no additional risk for retaining the placenta has been described. Here, anakinra was highly effective in suppressing disease activity of AOSD, was very well tolerated and affected neither the conception nor the development of the child in utero or post partum. However, according to existing guidelines patients should continue to receive firm advice about the potential risks of inhibiting IL1.

Acknowledgments

We are grateful to C Palla and MU Hoffmann for providing follow-up data and to S Schmid for helpful comments.

REFERENCES

Footnotes

  • Funding Funded by University Hospital Zurich, 8091 Zurich, Switzerland.

  • Competing interests None.

  • MR and US contributed equally.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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