Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

Objective To develop an evidence‐based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). Methods We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. Results This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti‐Ro/SSA and/or anti‐La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre‐pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy‐compatible medications, and ongoing physician‐patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. Conclusion This guideline provides evidence‐based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low‐level data. We intend that this guideline be used to inform a shared decision‐making process between patients and their physicians on issues related to reproductive health that incorporates patients’ values, preferences, and comorbidities.

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“…Although the drug label suggests discontinuation of MTX before attempting pregnancy, data show no evidence for mutagenesis or teratogenicity .…”

Section: Results/recommendationsmentioning

confidence: 96%

“…In men with RMD who are planning to father a pregnancy, we conditionally recommend, based on a smaller body of evidence, continuing treatment with MTX, MMF, leflunomide, sulfasalazine, calcineurin inhibitors, and nonsteroidal antiinflammatory drugs (NSAIDs) ( ).…”

Section: Results/recommendationsmentioning

confidence: 99%

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Sammaritano

Bermas

Chakravarty

et al. 2020

Arthritis & Rheumatology

425

520

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“…It is recommended that men stop methotrexate three months before conception. Two recent observational studies did not find an increased risk of congenital malformations when methotrexate (<30 mg) was used 90 days before conception 20,21. Condoms are not required during pregnancy.…”

Section: Methotrexatementioning

confidence: 97%

Immunomodulatory drugs in pregnancy and lactation

Paizis

2019

Aust Prescr

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SUMMARY Pregnancy presents challenges for women with autoimmune diseases. It is associated with significant physiological, hormonal and immunomodulatory changes which are complex and vary according to the stage of pregnancy Pregnancy planning and counselling should be offered Autoimmune diseases such as rheumatoid arthritis tend to improve in pregnancy while systemic lupus erythematosus may increase in activity During pregnancy the chosen regimen should control or prevent underlying disease activity and minimise risk to the fetus. Ideally, women should be on a stable regimen before conception Poorly controlled disease is associated with poor outcomes for both mother and fetus, such as higher risks of pre-eclampsia, early delivery and growth restriction of the fetus Postpartum, there is a sudden fall in hormone concentrations, and a switch to a pro-inflammatory state. This increases the risk of relapse of many autoimmune diseases in particular rheumatoid arthritis, Crohn’s disease and autoimmune hepatitis Many drugs are compatible with breastfeeding, but there are limited data on many of the new drugs

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“…Data regarding preconception exposure to MTX in men are reassuring, and, indeed, recent BSR guidelines state there is no need for men wishing to father children to stop MTX [154]. A study involving a very large cohort concluded that paternal exposure to MTX within 90 days before pregnancy was not associated with congenital malformations, stillbirths, and preterm birth [155]. Older recommendations suggest to stop MTX three months prior to conception, but this is not evidenced by an understanding of the impact of MTX on spermatogenesis or paternal-mediated teratogenicity, but rather relies on the timeframe of spermatogenesis [156].…”

Section: How To Get the Most Out Of Mtx As A First-line Treatment?mentioning

confidence: 99%

How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy

Taylor

Balsa

et al. 2019

JCM

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Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. In this article, we provide an evidence-based discussion as to how to achieve the best outcomes with this versatile drug in the context of a treat-to-target strategy for the management of RA.

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Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

Cited by 27 publications

References 25 publications

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Immunomodulatory drugs in pregnancy and lactation

How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy

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