When is prednisone indicated in antiphospholipid antibody syndrome (APAS) and what is the recommended dosing regimen?

Prednisone in Antiphospholipid Antibody Syndrome

Prednisone is NOT routinely recommended for antiphospholipid antibody syndrome and should generally be avoided except in specific refractory obstetric cases or when treating concurrent autoimmune conditions like systemic lupus erythematosus. 1

Primary Treatment Approach for APS

Non-Pregnant Patients with Thrombotic APS

• Anticoagulation with warfarin (target INR 2-3) is the standard treatment, NOT prednisone 1
• Aspirin 75-100 mg daily is recommended for asymptomatic patients with high-risk antiphospholipid profiles (triple-positive, double-positive, or isolated lupus anticoagulant) 1
• Direct oral anticoagulants should be avoided in favor of vitamin K antagonists 1

Pregnant Patients with Obstetric APS

• The strongly recommended first-line treatment is low-dose aspirin (81-100 mg daily) PLUS prophylactic-dose LMWH throughout pregnancy, NOT prednisone 1
• This combination has demonstrated approximately 75% live birth rates in obstetric APS 1
• Treatment should begin early in pregnancy (before 16 weeks) and continue through delivery 1

When Prednisone May Be Considered

Refractory Obstetric APS (Conditional Recommendation Against)

• The 2020 American College of Rheumatology guideline conditionally recommends AGAINST using prednisone for refractory obstetric APS (cases failing standard aspirin plus heparin therapy) 1
• Historical studies from the 1990s showed prednisone 40 mg daily tapered to 5 mg maintenance combined with aspirin achieved live births, but this approach has been abandoned due to significant maternal risks 2, 3
• Even when lower doses were used and tapered after midpregnancy, prednisone was associated with osteomalacia and preterm delivery (often from premature rupture of membranes) 2

Concurrent Autoimmune Disease

• Prednisone may be necessary when APS coexists with active systemic lupus erythematosus or other autoimmune conditions requiring corticosteroid therapy 1, 2
• In these cases, maintenance doses of glucocorticoids should be continued throughout pregnancy at the lowest effective dose 1

Critical Pitfalls to Avoid

Historical Practice No Longer Recommended

• Older protocols using high-dose prednisone (40-60 mg daily) for obstetric APS are obsolete 2, 3
• A randomized trial demonstrated equivalent live birth rates (~75%) with heparin versus prednisone, but heparin had superior safety 2
• Subsequent evidence showed adding heparin to aspirin is superior to aspirin alone, making prednisone unnecessary 2

Maternal and Fetal Risks

• Prednisone increases risk of gestational diabetes, hypertension, osteoporosis, preeclampsia, and preterm delivery 1, 2
• The 25% pregnancy loss rate that occurs despite standard therapy (aspirin plus LMWH) has NOT been shown to improve with addition of prednisone or increased LMWH doses 1

Alternative Adjunctive Therapies

• Hydroxychloroquine may be conditionally added to aspirin plus LMWH in primary APS, as recent small studies suggest it may decrease complications 1
• Intravenous immunoglobulin is conditionally recommended AGAINST for refractory cases, as it has not been demonstrably helpful 1

Asymptomatic Antiphospholipid Antibody-Positive Patients

• No prophylactic therapy is recommended for asymptomatic aPL-positive patients without pregnancy complications or thrombosis history 1
• Aspirin 81-100 mg daily may be conditionally recommended for preeclampsia prophylaxis in pregnant women with positive aPL who don't meet APS criteria 1
• Individual high-risk circumstances (triple-positive aPL, strongly positive lupus anticoagulant, advanced maternal age, IVF pregnancy) may warrant aspirin plus prophylactic heparin after physician-patient discussion 1