The latest British recommendations for the use of anti-rheumatic drugs during pregnancy and lactation
1. Recommendations for the use of glucocorticoids during pregnancy and lactation
(i) Prednisolone can be used in early and late pregnancy (level of evidence 1++, recommendation level A, strength of agreement 100%).
(ii) Prednisolone can be used during lactation (Level of Evidence 2-, Grade of Recommendation D, Strength of Agreement 98.9%).
(iii) Prednisolone is available for paternal use (Level of Evidence 2+, Grade of Recommendation D, Strength of Consistency 98.9%).
(iv) Methylprednisolone has the same placental transfer rate as prednisolone and possesses the same anti-inflammatory effect as 80% prednisolone dose, so the drug can be used during lactation, pregnancy and paternity (Level of Evidence 4, Grade of Recommendation D, Strength of Agreement 93.7%).
2. Recommendations for the use of hydroxychloroquine during pregnancy and lactation
(i) Hydroxychloroquine is one of the treatment options for women with rheumatic diseases who are preparing for pregnancy and should be used continuously during pregnancy (Level of Evidence 1++, Grade of Recommendation A, Strength of Agreement 100%).
(ii) Hydroxychloroquine can be used during lactation (Level of Evidence 4, Grade of Recommendation D, Strength of Agreement 98.9%).
(iii) Hydroxychloroquine may also be used in male patients who are preparing for pregnancy (Level of Evidence 2-, Recommendation Grade D, Consistency Strength 98.9%).
3. Recommendations for methotrexate use during pregnancy and lactation
(i) Methotrexate should not be used at any dose during pregnancy and should be discontinued 3 months prior to preparation for pregnancy (Level of Evidence 2-, Recommendation Grade D, Consistency Strength 100%).
(ii)Female patients who have used low-dose methotrexate in the 3 months prior to preparation for pregnancy should be supplemented with folic acid (5 mg/day) prior to and throughout pregnancy (Level of Evidence 1, Grade of Recommendation B, Strength of Agreement 98.4%).
(iii) Unintended pregnancy while using low-dose methotrexate should result in immediate discontinuation of the drug and continued folic acid supplementation (5 mg/day), and fetal risk should be closely assessed under the direction of a local physician (Level of Evidence 4, Grade of Recommendation D, Strength of Agreement 100%).
(iv) Methotrexate is not recommended for use during lactation due to theoretical risks and lack of sufficient evidence (Level of Evidence 4, Recommendation Grade D, Consistency Strength 100%).
(v) Based on limited evidence, low doses of methotrexate may be used by the parent (Level of Evidence 2+, Grade of Recommendation D, Strength of Agreement 95.8%).
4. Recommendations for the use of salazosulfapyridine during pregnancy and lactation
(i) Salazosulfapyridine may be used during pregnancy but should be accompanied by folic acid supplementation (5 mg/day) (Level of Evidence 2+, Grade of Recommendation C, Consistency Strength 100%).
(ii) Mothers of full-term healthy newborns may use salazosulfapyridine during lactation (Level of Evidence 4, Grade of Recommendation D, Consistency Strength 100%).
(iii) Use of salazosulfapyridine in men may reduce fertility, but there is no evidence that stopping salazosulfapyridine 3 months prior to pregnancy preparation improves the chances of pregnancy. Unless pregnancy is delayed for more than 12 months, other causes of infertility should be sought (level of evidence 3, recommendation level D, concordance strength 97.4%).
5. Recommendations for the use of leflunomide during pregnancy and lactation
(i) Based on the limited evidence, leflunomide may not be a human teratogen, but it is still not recommended for use in women who are planning to become pregnant (Level of Evidence 2+, Grade of Recommendation C, Strength of Agreement 100%).
(ii) Female patients on leflunomide who are planning to become pregnant should discontinue the drug prior to changing to a drug that can be used during pregnancy for elution with abciximide (Level of Evidence 2+, Grade of Recommendation C, Consistency Strength 100%).
(iii)
If eluted, no human studies have found an increased incidence of congenital malformations with leflunomide. Therefore, in the event of an unintended pregnancy while using leflunomide, the drug should be discontinued immediately and the disease should be eluted with abciximide until the drug concentration is not detectable in plasma (Level of Evidence 2+, Grade of Recommendation C, Strength of Agreement 98.9%).
(iv) There is no evidence of leflunomide secretion into breast milk and therefore the drug is not recommended for use during lactation (Level of Evidence 4, Grade of Recommendation D, Consistency Strength 100%).
(v) Based on the very limited evidence, leflunomide is recommended for use in men during pregnancy preparation (Level of Evidence 4, Grade of Recommendation D, Strength of Agreement 98.9%).
6. Recommendations for the use of azathioprine during pregnancy and lactation
(i) Azathioprine at ≤2 mg per kg body weight per day may be used during pregnancy (Level of Evidence 2++, Grade of Recommendation B, Consistency Strength 100%).
(ii) Azathioprine may be used during lactation (Level of Evidence 2-, Level of Recommendation D, Consistency Strength 99.5%).
(iii) Azathioprine may be used in men during pregnancy preparation (Level of Evidence 2+, Grade of Recommendation D, Consistency Intensity 100%).
7. Recommendations for cyclosporine use during pregnancy and lactation
(i) The lowest effective dose of cyclosporine may be used during pregnancy (Level of Evidence 1, Level of Recommendation B, Consistency Strength 100%).
(ii) Cyclosporine may also be used in lactating women (Level of Evidence 3, Level of Recommendation D, Consistency Strength 100%).
(iii) Based on limited evidence, cyclosporine is suggested to be used in men during pregnancy preparation (Level of Evidence 2-, Recommendation Grade D, Consistency Strength 98.9%).
8. Recommendations for tacrolimus use during pregnancy and lactation
(i) The lowest effective dose of tacrolimus may be used during pregnancy (Level of Evidence 2-, Recommendation Grade D, Consistency Strength 99.5%).
(ii) Tacrolimus may also be used in lactating women (Level of Evidence 3, Grade of Recommendation D, Consistency Strength 99.5%).
(iii) Based on limited evidence, cyclosporine is suggested to be used in men during pregnancy preparation (Level of Evidence 2-, Recommendation Grade D, Consistency Strength 98.4%).
9. Recommendations for cyclophosphamide use during pregnancy and lactation
(i) Cyclophosphamide is a teratogenic agent and is reproductively toxic, so it should only be considered in life-threatening situations (Level of Evidence 2, Recommendation Level C, Strength of Agreement 100%).
(ii) There is no evidence to recommend the use of cyclophosphamide during lactation (Level of Evidence 4, Recommendation Level D, Consistency Strength 100%).
(iii) Cyclophosphamide is not recommended for use in men during pregnancy preparation (Level of Evidence 4, Recommendation Grade D, Consistency Strength 98.4%).
10. Recommendations for the use of mycophenolate mofetil during pregnancy and lactation
(i) Mycophenolate esters are contraindicated during pregnancy (Level of Evidence 2-, Grade of Recommendation D, Strength of Agreement 100%).
(ii) Discontinue mycophenolate at least 6 weeks prior to planned pregnancy (Level of Evidence 3, Level of Recommendation D, Consistency Strength 100%).
(iii) There is a lack of information on the secretion of mycophenolate into breast milk, so it is not recommended for use during lactation (Level of Evidence 4, Grade of Recommendation D, Consistency Strength 99.5%).
(iv) Based on very limited evidence, mycophenolate can be used during male pregnancy preparation (Level of Evidence 2-, Grade of Recommendation D, Consensus Strength 98.9%).
11. Recommendations for IVIG use during pregnancy and lactation
(i) IVIG can be used during pregnancy (Level of Evidence 1++, Grade of Recommendation D, Consensus Strength 98.9%).
(ii) IVIG can be used during lactation (Level of Evidence 4, Recommendation Grade D, Strength of Agreement 98.9%).
(iii) Based on good maternal compatibility, IVIG may be harmless to the organism (Level of Evidence 4, Grade of Recommendation D, Consistency Strength 98.9%).
12. Recommendations for the use of anti-tumor necrosis factor agents during pregnancy and lactation
(i) Infliximab may be continued until 16 weeks of gestation, whereas etanercept and adalimumab may be used until mid-pregnancy (Level of Evidence 2-, Grade of Recommendation D, Strength of Consistency 98.9%).
(ii) To ensure very low or no drug concentrations in cord blood at delivery, etanercept and adalimumab should be avoided in the second trimester and infliximab should be discontinued after 16 weeks. If the use of this class of drugs is continued into late gestation for control of active disease, live vaccines should be avoided in the postnatal infant until after 7 months of age (level of evidence 3, recommendation level D, strength of agreement 98.9%).
(iii) Certolizumab may be used during all 3 periods of pregnancy because it is less likely to cross the placenta than other TNF inhibitors (Level of Evidence 2-, Grade of Recommendation D, Consensus Strength 97.9%).
(iv) Golimumab may be used in early pregnancy (Level of Evidence 4, Grade of Recommendation D, Consistency Strength 97.9%).
(v) TNF inhibitors may be used during lactation, but caution is recommended (Level of Evidence 3, Grade of Recommendation D, Consensus Strength 98.4%).
(vi) Based on limited evidence, infliximab, etanercept, and adalimumab may be used in men during pregnancy preparation (Level of Evidence 2-, Recommendation Grade D, Consensus Strength 98.9%).
13. Recommendations for the use of rituximab during pregnancy and lactation
(i) Rituximab should be discontinued during the first 6 months of pregnancy. Limited evidence has not found rituximab to be a teratogenic agent, and its use only in mid- to late-pregnancy has been associated with neonatal B-cell defects. Accidental use of rituximab in early pregnancy is therefore likely to be harmless (level of evidence 2-, recommendation level D, strength of agreement 97.9%).
(ii) There is a lack of information on the use of rituximab during lactation (strength of agreement 100%).
(iii) Based on limited evidence, rituximab may be used during male pregnancy preparation (Level of Evidence 2-, Grade of Recommendation D, Strength of Consistency 98.4%).
14. Recommendations for tolimumab use during pregnancy and lactation
(i) Tolzumab should be discontinued at least 3 months before pregnancy, but its unintended use in early pregnancy may not be harmful (Level of Evidence 3, Grade of Recommendation D, Strength of Agreement 96.8%).
(ii) There is a lack of information on the use of tolzumab during lactation (strength of agreement 99.5%).
(iii) There is no information on the use of tolimumab in men during pregnancy preparation, but it is probably not harmful (level of evidence 4, level of recommendation D, strength of agreement 97.9%).
15. Recommendations for the use of anabolic acid during pregnancy and lactation
(i) The limited evidence for the use of anabolic agents during pregnancy is not sufficient to develop a recommendation, but their unintended use during early pregnancy is probably not harmful (Level of Evidence 2-, Grade D, Strength of Agreement 96.8%).
(ii) There is a lack of information on the use of anabolic acid during lactation (strength of agreement 100%).
(iii) There is no information on the use of anabolic acid in men during pregnancy preparation, but it is probably not harmful (Level of Evidence 4, Grade of Recommendation D, Strength of Agreement 98.9%).
16. Recommendations for the use of abciximab during pregnancy and lactation
(i) The limited evidence for the use of abciximab during pregnancy is not yet sufficient to develop a recommendation. However, accidental use during early pregnancy may not be harmful (level of evidence 3, recommendation level D, strength of agreement 98.9%).
(ii) There is a lack of information on the use of abatacept during lactation (strength of agreement 100%).
(iii) There is no information on the use of abatacept in men during pregnancy preparation, but it is probably not harmful (Level of Evidence 4, Level of Recommendation D, Strength of Consistency 98.9%)
17. Recommendations for the use of belimumab during pregnancy and lactation
(i) The limited evidence for the use of belimumab during pregnancy is not yet sufficient to develop a recommendation. However, accidental use in early pregnancy may not be harmful (level of evidence 3, recommendation level D, strength of agreement 100%).
(ii) There is a lack of information on the use of belimumab during lactation (strength of agreement 100%).
(iii) There is no information on the use of belimumab in men during pregnancy preparation, but it is probably not harmful (Level of Evidence 4, Recommendation Level D, Strength of Agreement 98.9%).