How to use medication during pregnancy in patients with systemic lupus erythematosus

Patients with systemic lupus erythematosus should undergo necessary assessment and medication adjustments before pregnancy, use drugs that are as safe as possible to maintain a stable state of disease, and avoid medications
that may negatively affect female fertility.
However, during pregnancy, necessary medical interventions
are still needed to control the condition.

Regarding medication during pregnancy, in 2016 the European Union Against Rheumatism published guidelines on the use of rheumatic drugs during pregnancy and lactation [1].
 

• Before planning pregnancy, women of childbearing age should be planned and treatment options adjusted;

• Treatment of patients with rheumatic diseases during pregnancy and lactation should be aimed at preventing or suppressing the mother's disease activity while avoiding harm to the foetus;

• The risks to the mother and fetus with drug treatment should be assessed versus the risks associated with no drug treatment;

• Drug therapy during pregnancy and lactation should be decided
in consultation with a rheumatologist, obstetrician-gynecologist and patient.

In addition, the specific medication should also take into account the clinical reality, and may be affected
by the stage of pregnancy and other factors.
Generally, the types of drugs used during pregnancy are antimalarials NSAIDs, glucocorticoids, immunosuppressants, and biologics [2].

Hydroxychloroquine

Studies to date have shown that hydroxychloroquine has no teratogenic effect and is safe
for use during pregnancy.
In addition, some data suggest that the use of HCQ also reduces the incidence of congenital heart block in high-risk fetuses in pregnant women who are positive for anti-Ro/SSA and anti-La/SSB antibodies [3].

Discontinuation of hydroxychloroquine during pregnancy often leads to worsening of SLE symptoms and increased glucocorticoid requirements, so continued use of hydroxychloroquine
during pregnancy is recommended.

NSAIDs 

For patients with SLE, commonly used nonselective NSAIDs include acetaminophen and aspirin
.
Both drugs can cross the placenta, inhibit the synthesis of prostaglandins, cause premature closure of the ductus arteriosus and fetal pulmonary hypertension, therefore, the use of aspirin and paracetamol should be reduced in doses, and avoided in the last 3 months of pregnancy
.
However, studies by Flint et al.
[4] have shown that aspirin can have a positive effect on mothers by preventing high blood pressure and pre-eclampsia, and many studies have proven that aspirin has no teratogenic effects, so it is recommended to take low doses of aspirin throughout pregnancy
.

Glucocorticoids

Glucocorticoids are the mainstay
of treatment for pregnant women with SLE.
After rigorous preconception evaluation, SLE pregnant patients have low disease activity, and after the hard palate formation period, the lowest effective dose of glucocorticoids (prednisone 10 mg/day) is recommended to control the condition and monitor the condition closely [5].

The course of pregnancy may lead to severe disease activity, such as lupus crisis, glucocorticoid pulse can be used to induce remission, the medication regimen is: prednisone [1~1.
5 mg/(kg· d)] or methylprednisolone (500 ~ 1 000mg/d), 3d is 1 course of treatment
.
Pregnant women receiving glucocorticoids should be regularly monitored for possible pre-eclampsia The risk of gestational diabetes, hypertension and infection, and assuming that its HAP axis function is inhibited, prednisone should be changed to hydrocortisone (100~200 mg/d) in the peripartum period to prevent acute adrenal crisis during delivery [6].

immunosuppressant

Azathioprine is the only immunosuppressant
allowed during pregnancy.
Although azathioprine can cross the placenta, it is converted to the inactive metabolite thiourea and therefore has a limited
effect on the fetus.
Studies by Flint et al.
[6] showed no increase in spontaneous abortion rates in patients treated with azathioprine [<2 mg/(kg·d)].
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Biologics

Belilumab, a humanized anti-B lymphocyte stimulator (BLyS), is currently the only biologic approved
for SLE treatment.
Experimental studies conducted in monkeys have shown that although it can cross the placenta and may cause a decrease in the number of fetal B lymphocytes, belimumab has no teratogenic effect and does not cause other adverse reactions
.
However, there is no experimental data on its use during pregnancy, so basilizumab is still a contraindication for pregnant women with lupus
.

In conclusion, during pregnancy, reasonable and effective pharmacological intervention in patients with SLE is important for good outcomes for the mother and fetus
.

References

【1】Gotestam Skorpen C, Hoeltzenbein M, Tincani A, et al.
The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation[J].
2016, 75(5): 795-810.

【2】Kavanaugh A, Cush JJ, Ahmed MS, et al.
Proceedings from the American College of Rheumatology Reproductive Health Summit: the management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases[J].
Arthritis Care Res (Hoboken), 2015, 67(3): 313-325.

【3】Mekinian A, Lazzaroni MG, Kuzenko A, et al.
The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome : Data from a European multicenter retrospective study [J].
Autoimmun Rev, 2015, 14(6): 498-502.

【4】Flint J, Panchal S, Hurrell A, et al.
BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part II: analgesics and other drugs used in rheumatology practice [J].
Rheumatology (Oxford), 2016, 55(9): 1698-1702.

【5】Flint J, Panchal S, Hurrell A, et al.
BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: stan- dard and biologic disease modifying anti-rheumatic drugs and corticosteroids[J].
Rheumatology (Oxford), 2016, 55(9): 1693-1697.

[6] Li Jing, Luo Manling, Zhong Mei Periconceptional management of pregnancy complicated with systemic lupus erythematosus[J].
Chinese Journal of Practical Gynecology and Obstetrics, 2016,32(10): 934-939