Systemic Lupus Erythematosus, Part II: Treatment
/So how do we manage lupus in pregnancy?
Medications
Hydroxychloroquine
Can decrease disease activity, prednisone use, and adverse pregnancy outcomes.
SMFM: We recommend that all patients with SLE, other than those with quiescent disease, either continue or initiate HCQ in pregnancy.
ACR: conditionally recommends starting HCQ in pregnant patients with SLE who are not on it.
Some investigators recommend that patients with quiescent disease who have anti-SSA, anti-SSB, or APLS to consider starting HCQ because some studies suggest improved maternal and fetal outcomes in this specific population.
Corticosteroids
Recommended where SLE is not controlled simply with HCQ
Un-fluorinated corticosteroids are largely inactivated by the placenta and preferred:
Prednisone, hydrocortisone, prednisolone.
Recent evidence suggests corticosteroids are not associated with fetal malformations
However, steroids use can increase risk of gestational diabetes, preeclampsia, FGR, PPROM and PTB
Other immunosuppressive agents
Azathioprine - ok to use, not usually associated with fetal teratogenicity
Cyclosporine - can also be used for refractory lupus flares
Tacrolimus - calcineurin inhibitor - can be used, and has been reported to be more effective than cyclosporine
What should I avoid?
Prolonged use of NSAIDs - can lead to oligohydramnios, increased risk of NEC, premature closure of ductus arteriosus, and pulmonary hypertension
Methotrexate discontinue 1-3 months prior to pregnancy due to teratogenicity
Mycophenolate discontinue at least 6 weeks before attempting pregnancy
Leflunomide - teratogen, and pregnancy should be delayed 2 years after use because of its long half-life and enterohepatic circulation
Biologics
There have been a lot used recently, including TNF-alpha inhibitors (ie. certolizumab, infliximab, adalimumab, golimumab) and other biologics
Certolizumab can be safely used throughout pregnancy
Decision to initiate or continue biologics should be made in collaboration with rheumatology and also be individualized for each patient
What about antenatal considerations?
APLS
If someone has met clinical and laboratory criteria for APLS, goal is to improve maternal, fetal, and neonatal outcomes.
For those who have not had previous thrombotic event: recommend prophylactic anticoagulation during pregnancy + 6 weeks postpartum
For those with history of thrombotic event: recommend therapeutic anticoagulation throughout pregnancy + 6 weeks postpartum
Antiphospholipid antibodies without APLS
Patients with antibodies, especially lupus anticoagulant, who don’t meet clinical criteria for APLS remain at risk for preeclampsia
The risk of other adverse pregnancy outcomes and optimal management remains unclear
Meta-analysis of those with asymptomatic APL antibodies with or without SLE found no difference in adverse pregnancy outcomes in those who had prophylactic treatment (aspirin) and those who did not
SMFM recommend treatment with low-dose aspirin alone (i.e., no prophylactic anticoagulation)
SSA, SSB antibodies
Given risk of neonatal lupus syndrome with or without SLE in those with these antibodies, recommendation is to treat
Treatment with HCQ throughout pregnancy has been proposed to decrease the occurrence of congenital heart block in at-risk fetuses
However, data is still lacking due to adequately powered clinical trials
Another method proposed is to screen for 1st and 2nd degree heart block with echocardiograms, and then use steroids to try and prevent 3rd degree heart block
However, in the PR Interval and Dexamethasone Evaluation (PRIDE) study, they showed that treatment with dexamethasone in some women did reverse first degree heart block
However, some first degree heart block resolved on its own
Several cases of complete heart block occurred without a graded progression through 1st and 2nd degree heart block
There is some retrospective data as well to look at this, but overall, the utility of screening for or treating early heart block remains unproven
Current studies ongoing = STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV Block Likely to Occur Quickly)
Current recommendation: steroids should not be used routinely for treatment of fetal heart block due to anti-SSA/SSB antibodies given their unproven benefits nad known risks
Serial fetal echos for assessment of PR interval not be routinely performed in patients with anti-SSA or SSB antibodies outside of clinical trial settings
Doppler assessment of fetal heart rate during routine prenatal visits can be used to screen for fetal complete heart block
Mild lupus flares
Clinical and lab evaluation of possible SLE flare
Physical exam, CBC, anti-dsDNA, complement levels
Start HCQ 200 mg BID, if not already on it
If already on it, can increase to 400 mg 2x/day
If not responding, then can start 15-20 mg of prednisone a day.
Severe lupus flares
Same clinical and lab evaluation
Can also look for preeclampsia
Start glucocorticoid dosage 1.0-1.5 mg/kg, then tapered per improvement
Hospitalization may be needed
Rheumatology consultation
Other recommendations in pregnancy and labor
Pre-pregnancy counseling
Patients with SLE should get prepregnancy counseling with MFM and rheumatology - discuss risks for both mom and fetus
In those with severe maternal risk, pregnancy should be discouraged
Active nephritis
Severe pulmonary, cardiac, renal, or neurologic disease
Recent stroke
Pulmonary hypertension
Antenatal Testing
Antenatal testing and serial growth scans recommended in patients with SLE due to increased risk of FGR and stillbirth
Currently no evidence to support optimal approach
Usually, will start interval growths at 28 and assess every 4 weeks
Fetal surveillance may start at around 32 weeks
Delivery considerations
Timing, mode, and management of delivery should be individualized
If uncomplicated, early delivery is not recommended, but can be considered at term - ie. at 39 weeks
If other complications, should manage per complication
Stress dose steroids in those with prolonged use of steroids
Postpartum management
Incidence of relapse or flare will increase in SLE - as with other autoimmune disease
Can discuss with rheumatology regarding treatment postpartum - not all patients will need prophylactic treatment
NSAIDs can be used for joint pain
Can breastfeed if desired (NSAIDs, HCQ, and corticosteroids are considered compatible by AAP)
Contraception
LARCs such as IUD (with or without levonorgestrel) and etonogestrel implants are good options for patients with SLE
Estrogen-containing oral contraceptives pose a theoretical risk for SLE flares
Can be used in patients with SLE
However, patients with history of active and severe SLE were excluded from randomized trials proving estrogen safety in those with SLE
Contraindicated in those with previous thrombosis or those with APLS
Progesterone only contraception is also safe