For rheumatism patients preparing for pregnancy, which drugs should be stopped and which should not be stopped?

*For medical professionals to read and reference Rheumatism patients who are preparing for pregnancy, quickly collect! Rheumatic and musculoskeletal diseases (RMDs) are a group of systemic diseases that mainly affect joints and surrounding tissues, including systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) ), rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, inflammatory myopathy, systemic vasculitis, spondyloarthritis,
etc.

Most RMDs are most common in women.
Except for giant cell arteritis, they can all occur during the reproductive years.
Long-term medication is required to maintain stable disease
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In addition, pregnancy in patients with RMDs can lead to serious adverse maternal and fetal outcomes, and the risk of pregnancy complications depends on diagnosis, disease activity and degree of impairment, drug use, presence of anti-SSA/Ro or anti-SSB/La, and antiphospholipid antibodies (aPL).

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Female patients with RMDs may face the risk of disease fluctuation or deterioration during pregnancy.
When rheumatology immunologists receive patients of childbearing age, they need to communicate with them about pregnancy plans, precautions during pregnancy, and maternal and child safety issues of drug use
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Before pregnancy, patients with RMDs should plan rationally for family planning under the guidance of specialists in rheumatology and immunology, obstetrics and gynecology, and neonatology
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In 2020, the American College of Rheumatology (ACR) formulated evidence-based guidelines on contraception, assisted reproductive technology, pregnancy assessment and management, drug selection and drug regimens for patients with RMDs [1]
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This article organizes the pregnancy preparation part of the guidelines to provide reference for the disease assessment, drug selection and drug regimen of RMDs patients who are preparing for pregnancy
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Pregnancy in patients with RMDs is at risk! The management of reproductive health problems in patients with RMDs is different from that in healthy people, and the risk of pregnancy complications in patients with RMDs is higher than that in healthy people
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Most patients with RMDs inevitably need to receive drug treatment before pregnancy to control disease activity, and not all drugs are suitable for use before pregnancy
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However, uncontrolled disease activity is in turn associated with adverse pregnancy outcomes
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Therefore, the disease control and medication regimens of such patients before pregnancy need to be discussed jointly by the rheumatology and immunization department and the reproductive medicine department
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Drug recommendations for RMDs patients who are preparing for pregnancy ■ The drugs recommended for men who are preparing for pregnancy are different from those of women.
The focus is mainly on fertility and drug teratogenicity.
However, there are few reports on the effects of drugs in men who are preparing for pregnancy on the fetus
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Studies have shown that the use of cyclophosphamide in men may affect sperm production or cause sperm gene mutations, so it should be discontinued 12 weeks before trying to conceive
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Thalidomide can be detected in male semen, and serious teratogenic problems have been found in pregnant women, so it is recommended to stop for at least 4 weeks
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Table 1 Medication for male patients with RMDs who are trying to conceive ■ Recommended medication for women who are planning to become pregnant The 2020 ACR guidelines strongly recommend that the drugs used by patients with RMDs before pregnancy include: hydroxychloroquine, sulfasalazine, colchicine, azathioprine or mercaptopurine, and certolizumab
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Methotrexate, mycophenolate mofetil, and cyclophosphamide are all teratogenic, so women should stop using them before trying to conceive
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At present, there is no relevant clinical research data on tofacitinib and baricitinib in women before pregnancy, but they are all small-molecule drugs that can be secreted through the placenta or breast milk, so they are not recommended for use
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Table 2 Female patients with RMDs who are trying to conceive RMDs patients with assisted reproduction RMDs patients have the same ability to conceive as normal women, but with age, some RMDs patients need to use assisted reproductive technology to conceive
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Assisted reproductive technology requires ovarian stimulation to increase estrogen levels, which can aggravate disease activity in patients with RMDs
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Therefore, it is recommended that patients with RMDs receive assisted reproductive therapy as soon as possible on the basis of stable disease, no complications, negative aPL, and the use of non-teratogenic drugs
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Preconception medication regimen for subfertile patients with pregnancy-intentional RMDs ■ aPL-positive or APSAPS is an autoimmune disease characterized by recurrent arteriovenous thrombosis, spontaneous abortion, thrombocytopenia, and persistent serum aPL positivity
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aPL antibodies are a major risk factor for spontaneous miscarriage and other adverse pregnancy outcomes
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① Patients with positive aPL but not in line with obstetric antiphospholipid syndrome (OAPS) nor thrombotic APS: the guidelines recommend the use of low-dose aspirin (81-100mg/d) to prevent preeclampsia (from 16 weeks of gestation) previously started and continued until delivery), but low molecular weight heparin and hydroxychloroquine are not recommended
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② OAPS patients: It is recommended to use low-dose aspirin in combination with prophylactic doses of low-molecular-weight heparin and hydroxychloroquine, but prednisone, therapeutic doses of heparin and injection of immune globulin are not recommended
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③ Patients with thrombotic APS: It is recommended to use low-dose aspirin and therapeutic-dose low-molecular-weight heparin and hydroxychloroquine throughout pregnancy and postpartum
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■ SLE guidelines recommend that all SLE patients take hydroxychloroquine during pregnancy, and users continue to use it before pregnancy
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It is recommended that all patients with SLE be started on low-dose aspirin in the first trimester
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SLE disease activity affects pregnancy outcomes, so it is recommended to assess disease activity by clinical presentation, physical examination, and laboratory test results at least every 3 months
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Conclusion Many drugs for the treatment of RMDs are teratogenic, and a large proportion of RMDs occur during reproductive age
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Therefore, when doctors receive patients of childbearing age, they need to communicate with them about pregnancy plans, inform them of precautions during pregnancy, and the safety of mothers and babies using drugs
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Develop the most appropriate medication regimen to reduce the risk of adverse pregnancy outcomes while controlling disease activity
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 Reference [1] Sammaritano LR, Bermas BL, Chakravarty EE, et al.
2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases[J].
Arthritis Rheumatol, 2020,72(4):529- 556.
DOI:10.
1002/art.
41191.
[2] Guo Juanjuan, Zhuang Siying, Duan Jie, et al.
Interpretation of "2020 American College of Rheumatology Management Guidelines for Reproductive Health of Patients with Rheumatic and Musculoskeletal Diseases"[J].
Modern Obstetrics and Gynecology Progress, 2021, 30(04):301-306.