ACR Releases Guideline to Managing Reproductive Health With Comorbid Rheumatic Disease

Pregnancy in women with rheumatic and musculoskeletal disease (RMD) may lead to serious maternal or fetal adverse outcomes, but the majority of women with RMD can have successful pregnancies with adequate planning, treatment, and monitoring, the American College of Rheumatology (ACR) said Monday as it released the first clinical practice guideline regarding the management of reproductive health in this population.

The 2020 Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases includes 12 ungraded good practice statements and 131 graded recommendations that are intended to guide care, except where indicated as being aimed at patients with specific conditions or antibodies present, such as systemic lupus erythematosus (SLE); antiphospholipid antibody, or APL (persistent moderate-to-high—titer anticardiolipin or anti–β2-glycoprotein I antibody or persistent positive lupus anticoagulant); or antiphospholipid syndrome (APS), either obstetric and/or thrombotic.

Taking into consideration patients’ values, preferences, and comorbidities, the guidelines, based on clinical evidence, are a pathway to a shared decision-making process between patients and their physicians, the ACR said.

The ACR said that “good practice statements are those in which indirect evidence is compelling enough that a formal vote was considered unnecessary.” They are presented as suggestions rather than formal recommendations.

While some of the recommendations are strong, many of the recommendations presented are conditional due to a lack of data. Pregnant women are not generally enrolled in clinical studies, and few maternal health studies focus on patients with these diseases, the ACR noted.

The recommendations are divided into 6 categories: medication use, contraception, assisted reproductive technology, fertility preservation with gonadotoxic therapy, menopausal hormone replacement therapy, and pregnancy assessment and management.

Medication Use (paternal and maternal)

The guidelines make a strong recommendation against use of cyclophosphamide (CYC) and thalidomide in men prior to attempting conception, and a strong recommendation against the use of nonsteroidal anti-inflammatory drugs in the third trimester.

For biologic medications, the guidelines conditionally recommend continuing anti—tumor necrosis factor inhibitor therapy with infliximab, etanercept, adalimumab, or golimumab prior to and during pregnancy. In addition, the guidelines strongly recommend continuation of certolizumab therapy prior to and during pregnancy; certolizumab does not contain an Fc chain and thus has minimal placental transfer.

The guidelines conditionally recommend continuing treatment with anakinra, belimumab, abatacept, tocilizumab, secukinumab, and ustekinumab while a woman is trying to conceive, but discontinuing once she is found to be pregnant.

In addition, the guidelines conditionally recommend continuing treatment with rituximab while a woman is trying to conceive, and conditionally recommend continuing rituximab during pregnancy if severe life- or organ-threatening maternal disease warrants.

Contraception

Patients with RMD typically underutilize effective contraception, the guidelines say, even though the risks of unplanned pregnancy include worsening or life-threatening disease activity as well as adverse pregnancy outcomes such as pregnancy loss, severe prematurity, and growth restriction. Congenital birth defects are another risk.

The guidelines specify a strong recommendation for women with rheumatic disease who do not have lupus or APS to use effective contraceptives. In addition, the guidelines provide a conditional recommendation to preferentially use highly effective intrauterine devices or a subdermal progestin implant.

In women who test positive for APL or APS, there is a strong recommendation against using combined estrogen-progestin contraceptives.

Assisted Reproductive Technology

Fertility is typically normal in women with RMD, assuming they have not received treatment with CYC, the authors said.

The authors strongly recommend proceeding with assisted reproductive technology if needed in women with uncomplicated RMD who are receiving pregnancy-compatible medications, whose disease is stable, and who are negative for APL.

They make more specific recommendations for patients who test positive for APL and suggest an anti—blood clotting procedure. However, the guidelines provide a conditional recommendation against increasing prednisone dosage during fertility therapy procedures in patients with lupus.

Fertility Preservation

For men, the guidelines state a good practice suggestion to cryopreserve sperm before CYC treatment in men, if they wish, and a conditional recommendation against testosterone co-therapy in men with rheumatic disease receiving CYC.

For women, the guidelines state a conditional recommendation for monthly gonadotropin-releasing hormone agonist co-therapy for premenopausal women with rheumatic disease who are receiving monthly CYC injections/infusions to prevent premature ovarian insufficiency.

Pregnancy Assessment and Management

The guidelines make a strong good practice suggestion to advise women who are considering pregnancy about the improved maternal and fetal outcomes associated with starting pregnancy during low disease activity.

The guidelines also make a conditional recommendation to treat patients lupus with low-dose aspirin daily (81-100 mg) starting in the first trimester. For women testing positive for APL who do not meet the criteria for obstetric or thrombotic APS, it is conditionally recommended to preventatively treat with a daily aspirin (81-100 mg) starting early in pregnancy and continuing through delivery.

Menopause and Hormone Replacement Therapy

The guidelines make a good practice suggestion to use hormone replacement therapy (HRT) in postmenopausal women with rheumatic disease who do not have lupus or have a positive APL test and who have severe vasomotor symptoms, have no contraindications, and desire treatment.

The guidelines make a conditional recommendation for HRT in women with lupus and without APL. They conditionally recommend against treating with HRT for women with asymptomatic APL and strongly recommend against hormone replacement therapy for women with any form of APS.