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ACR 2020 Reproductive Guidelines - Medication Use with Pregnancy

The American College of Rheumatology (ACR) has published guidelines to manage reproductive health issues in rheumatic disease (RMD) patients before, during and after pregnancy. In this second exerpt from their guidelines articles we present recommendations (and good clinical practice statements) for paternal rheumatology medication use by men with RMD and on conventional rheumatology medications and biologic use in pregnancy for women with RMD. 

The next issue (tomorrow) will present the recommendations regarding glucocorticoid use during pregnancy and medication use with lactation. 

The following is exerpted from the full manuscript. Please refer to the manuscript for more detail and evidence.

RMD Paternal Medication Use 

  • In men with RMD who are planning to father a child, we suggest discussing the use of medications prior to attempting to conceive a pregnancy.
  • In men with RMD who are initiating treatment with medications that may affect fertility (e.g. cyclophosphamide), we suggest discussing future pregnancy plans.
  • In men with RMD who are planning to father a child within three months:
    • Discontinue:
      • cyclophosphamide (strongly recommended)
      • thalidomide (conditionally recommended)
    • OK to continue (strongly recommended): 
      • hydroxychloroquine 
      • azathioprine/ 6-mercaptopurine
      • TNF inhibitors (infliximab, etanercept, adalimumab, golimumab, certolizumab)
      • colchicine 
    • Conditionally recommend continuation of:
      • leflunomide
      • mycophenolate mofetil
      • classic NSAIDs or Cox2 inhibitors
      • sulfasalazine
      • cyclosporine
      • tacrolimus
      • anakinra
      • rituximab 

RMD Maternal Rheumatology Medications in Pregnancy 

  • We suggest discussing the use of medications prior to attempting to conceive; we also suggest discussing future pregnancy plans when initiating treatment with medications that may affect fertility such as cyclophosphamide.
  • In women with inadvertent exposure to teratogenic medications during pregnancy, we strongly suggest immediate medication discontinuation and referral to a maternal-fetal-medicine specialist or genetics counselor.
  • Caveats on NSAID use:
    • If having difficulty conceiving, we conditionally recommend discontinuing NSAIDs while trying to conceive if disease control would not be compromised
    • If pregnant, we strongly recommend avoiding NSAIDs in the third trimester 
    • If pregnant, we conditionally recommend non-selective NSAIDs over Cox2-specific inhibitors as compatible with pregnancy in the first two trimesters 
  • In women who are pregnant or planning pregnancy:
    • Medications to AVOID:
      • We strongly recommend discontinuing methotrexate prior to attempting conception
      • We strongly recommend discontinuing mycophenolate mofetil/mycophenolic acid at least six weeks prior to attempting conception
      • We strongly recommend discontinuing thalidomide prior to attempting conception
      • We strongly recommend discontinuing cyclophosphamide prior to attempting conception
    • In the case of life- or organ- threatening maternal disease in which there are no alternative therapies we conditionally recommend initiating cyclophosphamide in the second or third trimester 
    • If an inadvertent pregnancy occurs while using leflunomide, we strongly recommend discontinuing leflunomide and initiating a cholestyramine washout until drug levels are undetectable 
    • If treated with leflunomide within 24 months, we strongly recommend demonstrating that blood levels are undetectable, or initiating a cholestyramine washout until drug levels are undetectable, prior to attempting conception 
    • Safe/continued use during pregnancy (strongly recommended):
      • hydroxychloroquine
      • sulfasalazine
      • azathioprine/6-mercaptopurine
      • colchicine 
    • Conditionally recommend during pregnancy:
      • cyclosporine
      • tacrolimus 

Biologic Use in RMD Associated with Pregnancy

  • TNF alpha inhibitor therapy
    • We strongly recommend continuing certolizumab therapy prior to and during pregnancy 
    • We conditionally recommend continuing TNF-inhibitor therapy (infliximab, etanercept, adalimumab, golimumab) prior to and during pregnancy
  • Rituximab: We conditionally recommend continuing rituximab through conception
    • We conditionally recommend using rituximab during pregnancy in the setting of severe, life or organ threatening maternal disease 
  • Non-TNFi biologic agents (anakinra, belimumab, abatacept, tocilizumab, secukinumab, ustekinumab)
    • We conditionally recommend continuing therapy through conception.
    • We conditionally recommend discontinuing therapy during pregnancy.
  • Novel, small molecule targeted therapies (tofacitinib, baracitinib, apremilast): the committee was unable to offer recommendations regarding use during pregnancy due to lack of data (EDITORS NOTE: the same recommendation would likely apply to upadacitinib, which was approved after these guidelines were written).

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Disclosures
The author has no conflicts of interest to disclose related to this subject