The EULAR points to consider for use of antirheumatic drugs before pregnancy and during pregnancy and lactation
| Overarching principles | ||
| A | Family planning should be addressed in each patient of reproductive age and adjustment of therapy considered before a planned pregnancy. | |
| B | Treatment of patients with rheumatic disease before/during pregnancy and lactation should aim to prevent or suppress disease activity in the mother and expose the fetus/child to no harm. | |
| C | The risk of drug therapy for the child should be weighed against the risk that untreated maternal disease represents for the patient and the fetus or child. | |
| D | The decision on drug therapy during pregnancy and lactation should be based on agreement between the internist/rheumatologist, gynaecologist/obstetrician and the patient, and including other healthcare providers when appropriate. | |
| Points to consider for use of antirheumatic drugs in pregnancy* | Grade of recommendation† | |
| 1 | csDMARDs‡ proven compatible with pregnancy are hydroxychloroquine, chloroquine, sulfasalazine, azathioprine, ciclosporin, tacrolimus and colchicine. They should be continued in pregnancy for maintenance of remission or treatment of a disease flare. | B |
| 2 | csDMARDs‡ methotrexate, mycophenolate mofetil and cyclophosphamide are teratogenic and should be withdrawn before pregnancy. | B |
| 3 | Non-selective COX inhibitors (non-steroidal anti-inflammatory drugs, NSAIDs) and prednisone should be considered for use in pregnancy if needed to control active disease symptoms. NSAIDs should be restricted to the first and second trimesters. | B |
| 4 | In severe, refractory maternal disease during pregnancy methylprednisolone pulses, intravenous immunoglobulin or even second or third trimester use of cyclophosphamide should be considered. | D |
| 5 | csDMARDs‡, tsDMARDs§ and anti-inflammatory drugs with insufficient documentation concerning use in pregnancy should be avoided until further evidence is available. This applies to leflunomide, mepacrine, tofacitinib and selective COX II inhibitors. | B–D |
| 6 | Among bDMARDs¶ continuation of tumour necrosis factor (TNF) inhibitors during the first part of pregnancy should be considered. Etanercept and certolizumab may be considered for use throughout pregnancy due to low rate of transplacental passage. | B |
| 7 | bDMARDs¶ rituximab, anakinra, tocilizumab, abatacept, belimumab and ustekinumab have limited documentation on safe use in pregnancy and should be replaced before conception by other medication. They should be used during pregnancy only when no other pregnancy-compatible drug can effectively control maternal disease. | D |
| Points to consider for use of antirheumatic drugs during lactation* | Grade of recommendation† | |
| 1 | csDMARDs‡ and anti-inflammatory drugs compatible with breast feeding should be considered for continuation during lactation provided the child does not have conditions that contraindicate it. This applies to hydoxychloroquine, chloroquine, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, prednisone, immunoglobulin, non-selective COX inhibitors and celecoxib. | D |
| 2 | csDMARDs‡, tsDMARDs§ and anti-inflammatory drugs with no or limited data on breast feeding should be avoided in lactating women. This applies to methotrexate, mycophenolate mofetil, cyclophosphamide, leflunomide, tofacitinib and cyclooxygenase II inhibitors other than celecoxib. | D |
| 3 | Low transfer to breast milk has been shown for infliximab, adalimumab, etanercept and certolizumab. Continuation of TNF inhibitors should be considered compatible with breast feeding. | D |
| 4 | bDMARDs¶ with no data on breast feeding such as rituximab, anakinra, belimumab, ustekinumab, tocilizumab and abatacept should be avoided during lactation if other therapy is available to control the disease. Based on pharmacological properties of bDMARDs¶, lactation should not be discouraged when using these agents, if no other options are available. | D |
*Level of evidence is given for each drug separately in table 2.
†A Category I evidence from meta-analysis of randomised controlled trials (1A) or from at least one randomised controlled trial (1B)
B Category II evidence from at least one controlled study without randomisation (2A) or from at least one type of quasi-experimental study (2B), or extrapolated recommendations from category I evidence.
C Category III evidence from descriptive studies, such as comparative studies, correlation studies or case-control studies (3), or extrapolated recommendation from category I or II evidence.
D Category IV evidence from expert committee reports or opinions and/or clinical experience of respected authorities (4), or extrapolated recommendation from category II or III evidence.10
‡Conventional synthetic DMARDs.
§Targeted synthetic DMARDs.
¶Biologic DMARDs.