INTRODUCTION
The course and outcome of pregnancy can be affected by the activity of the inflammatory rheumatic disease itself and by the drugs we use. Therapeutic progress in the treatment of inflammatory rheumatic diseases has led to the widespread use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) with different mechanisms of action, including their biosimilar versions, as well as a new class of targeted synthetic DMARDs (tsDMARDs). There is an increasing number of publications on the use of DMARDs in pregnancy, but the development of new drugs is inevitably accompanied by uncertainty about their use in pregnancy, which can lead to unnecessary medication discontinuation. Medication discontinuation before or during early pregnancy potentially increases the risk of disease activity and exacerbation during pregnancy, so it is extremely important to weigh the potential benefit to the foetus against the risk of loss of disease control before making a decision to choose or change therapy.
The aim of this review is to analyse and consolidate the current guidelines of international and some national professional societies of rheumatology: the EULAR (the European Alliance of Associations for Rheumatology), the BCR (the British Society for Rheumatology) and the ACR (the American College of Rheumatology) (1–3) and provide updated information in one place on the compatibility of the most commonly prescribed immunomodulators and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with immune-mediated inflammatory rheumatic diseases during conception, pregnancy and breastfeeding.
According to the latest British, American and European guidelines, the general recommendations for prescribing immunomodulators and NSAIDs in pregnancy are as follows:
1. It is recommended to consult with your physician in the period pre-conception with the aim of optimising the control of rheumatic disease before pregnancy, the timing of pregnancy and medications to be used before/during/after pregnancy, including contraception.
2. The risks and benefits of prescribed medications for the mother as well as the child should be explained thoroughly and clearly documented.
3. Drugs that are contraindicated in pregnancy should be replaced by drugs that are compatible with pregnancy, preferably in the period pre-conception in order to establish the control of the disease with the new drug.
4. If there is no suitable drug that would be compatible with pregnancy, the control of the mother’s severe/life-threatening disease activity should take precedence over concern for potential foetal outcomes.
5. The use of all biologic drugs can be continued throughout the pregnancy if they are necessary to establish control over the activity of the mother’s severe/life-threatening disease.
6. The immunisation schedule of a newborn/infant after in utero exposure to a biologic drug depends on the time of exposure, bioavailability and the mechanism of action of the drug.
7. When the mother’s disease is well controlled, the minimum effective dose of the immunomodulator should be used, and medication discontinuation should be considered in cases where there is a low risk of disease exacerbation.
8. Some drugs can reduce male fertility, but paternal exposure has not been linked to the foetal development or adverse pregnancy outcomes (1–3)
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Due to their analgesic and anti-inflammatory activity, non-selective non-steroidal anti-rheumatic drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) are used in a number of inflammatory rheumatic diseases, and they have a special role in the medical treatment of spondyloarthritis, osteoarthritis and gout.
Non-selective NSAIDs and COX-2 inhibitors are associated with an increased risk of unruptured follicle syndrome, which is why it is recommended to avoid them in case of reduced female fertility (2, 4). It is worth noting that a higher risk was found in patients with inactive rheumatic disease and that the risk of this reversible syndrome is higher with the use of COX-2 inhibitors (etoricoxib) than with non-selective NSAIDs (5). Large retrospective studies have conflicting conclusions about the safety of non-selective NSAIDs in the first trimester (5). The EULAR considers that non-selective NSAIDs are compatible with pregnancy in the first and second trimester (3). Considering that certain studies have found an increased risk for spontaneous abortion and malformations (6–8), the BCR recommends that non-selective NSAIDs be used only intermittently in the first and second trimester (4) and the ACR also considers them to be conditionally compatible with pregnancy (2). After the 30th week of pregnancy, non-selective NSAIDs are recommended to be completely discontinued due to the risk of premature closure of the ductus arteriosus (2–4). The FDA (the U.S. Food and Drug Administration) recommendation from 2020 is to avoid all non-selective NSAIDs from the 20th week of pregnancy instead of the previously recommended 30th week. This recommendation was made based on the data on the increased risk of oligohydramnios and kidney damage from the 20th week of pregnancy (4). COX-2 inhibitors are recommended to be avoided due to limited data on their use in pregnancy (2–4). Non-selective NSAIDs, especially ibuprofen, are compatible with breastfeeding (2, 4). Among COX-2 inhibitors, the EULAR highlights the importance of celecoxib, for which there is evidence that corroborates the claim that it is compatible with breastfeeding (9), while other COX-2 inhibitors are not recommended for use during breastfeeding (2–4).
GLUCOCORTICOIDS
Glucocorticoids that are most often used in the treatment of rheumatic diseases (prednisone, methylprednisolone) are metabolised in the placenta, so less than 10% of the active drug reaches the foetus (10). Prednisone and methylprednisolone are compatible with pregnancy with mandatory monitoring of blood pressure and blood glucose. Whenever possible, the dose of prednisone should be less than 20 mg/day, i.e. the lowest dose necessary to establish control over the mother’s disease. Prednisone and methylprednisolone are compatible with breastfeeding. After the use of prednisone in a dose of > 20 mg, it is recommended to delay breastfeeding for 4 hours (1–3).
Fluorinated glucocorticoids (dexamethasone, betamethasone) cross the placenta unhindered and are used in the prevention and treatment of premature foetal respiratory distress or congenital heart block.
Intra-articular and intramuscular injections can be safely administered throughout pregnancy (3).
SYNTHETIC ANTIMALARIALS
Due to its immunomodulatory effect, hydroxychloroquine is most often used in the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The dose of hydroxychloroquine used in rheumatic diseases is ≤ 400 mg/day, and it is the DMARD of choice for women who are in the course of pregnancy planning. Based on numerous studies and reports in which no effect on the duration of pregnancy and birth weight, as well as no increased risk or specific pattern of congenital malformations were found, it was noted that hydroxychloroquine is considered compatible with pregnancy at a dose of ≤ 400 mg/day. Hydroxychloroquine is compatible with breastfeeding (1, 2). There are no recommendations regarding the use of chloroquine during pregnancy/breastfeeding in the guidelines analysed in this review.
SULFASALAZINE
Sulfasalazine is a conventional synthetic DMARD (csDMARD) used in rheumatology in the treatment of RA, PsA and other seronegative rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Sulfasalazine is compatible with pregnancy, and the additional recommendation of the EULAR is to limit the dose to 2 g per day (3). When prescribing sulfasalazine, it is important to recommend patients to take it with folic acid in a dose of 5 mg/day in the period pre-conception and throughout the first trimester. Sulfasalazine is compatible with breastfeeding of healthy term infants (1, 2). Breastfeeding is not recommended for sick children, premature infants, in cases of hyperbilirubinemia or glucose-6-phosphate dehydrogenase deficiency. (11).
AZATHIOPRINE
Azathioprine is an antimetabolite immunosuppressant used in the treatment of numerous inflammatory rheumatic diseases, e.g. SLE, idiopathic inflammatory myopathies (IIM) and systemic vasculitis. Azathioprine is compatible with pregnancy. The EULAR recommendation is to limit the dose to 2 mg/kg/day (3). Azathioprine is compatible with breastfeeding, but is considered to be conditionally recommended by the ACR due to the proven low transfer rate into breast milk (1, 2).
COLCHICINE AND DAPSONE
Colchicine is an antimitotic alkaloid with anti-inflammatory activity that is used in the treatment of gout and other autoinflammatory diseases, e.g. familial Mediterranean fever and Behçet’s disease. Colchicine in a dose of up to 2 mg per day is compatible with pregnancy (1, 2). The EULAR recommendation is to limit the dose to 1 mg/day (3). Colchicine is compatible with breastfeeding. After the use of colchicine, it is recommended to delay breastfeeding for 2 — 4 hours (4).
Dapsone is a sulfone antibiotic (antileprotic) with anti-inflammatory properties that is used in the treatment of cutaneous lupus erythematosus, neutrophilic dermatoses and certain forms of vasculitis. Dapsone is compatible with pregnancy and breastfeeding. Due to the risk of haemolytic anaemia, regular screening of newborns/infants for signs of haemolysis is recommended (4).
CYCLOSPORINE AND TACROLIMUS
Cyclosporine and tacrolimus are selective calcineurin inhibitors that are most often used in rheumatology for the treatment of SLE.
Cyclosporine and tacrolimus are considered to be compatible by the BSR and the EULAR, while the ACR considers them conditionally compatible during pregnancy and breastfeeding. Due to the higher risk of arterial hypertension, preeclampsia and gestational diabetes, regular monitoring of arterial pressure, urea, creatinine, glucose and drug concentration during pregnancy is recommended. Cyclosporine and tacrolimus can transfer into breast milk in small amounts and, although they have not been detected in the blood concentration of breastfed infants and no adverse effects have been reported, the ACR considers them conditionally recommended during breastfeeding (1–3).
METHOTREXATE
Methotrexate is a csDMARD used in the treatment of numerous inflammatory rheumatic diseases and it is the gold standard in the treatment of RA. Methotrexate has teratogenic effects and is contraindicated in pregnancy and breastfeeding in all doses. It is advised to discontinue methotrexate 1 — 3 months before the planned pregnancy. In case of exposure to methotrexate in a low dose (≤ 25 mg/week) within a month in the period pre-conception, patients are advised to take folic acid in a dose of 5 mg/day until the 12th week of pregnancy. In case of an unplanned pregnancy on a low dose of methotrexate (≤ 25 mg/week) the risk to the foetus is minimal. It is recommended to discontinue methotrexate immediately, to take folic acid in a dose of 5 mg/day and to be under close monitoring by an obstetrician due to the risk of developing foetal anomalies. Exposure of the foetus to high doses of methotrexate (500 mg/m2) used for cancer treatment represents a high risk for serious malformations and is an indication for induced abortion. A negligible amount of methotrexate is excreted in breast milk, but due to the theoretical risk and insufficient data, it is not recommended to use it during breastfeeding (1–3).
LEFLUNOMIDE
Leflunomide is a csDMARD used in the treatment of RA, PsA and other types of seronegative arthritis.
Leflunomide has not been shown to have teratogenic effects. An analysis of over 700 pregnancies exposed to leflunomide did not show an increased risk for adverse effects (12), but given the fact that there is insufficient evidence that confirms that it is compatible with pregnancy, its use is not recommended before or during pregnancy. It is recommended to discontinue leflunomide 24 months in the period pre-conception or perform a cholestyramine washout (cholestyramine at a dose of 8 g three times a day for 11 days or cholestyramine at a dose of 4 g three times a day if cholestyramine at a dose of 8 g three times a day is not well tolerated). In cases of unplanned pregnancies during which the patients have been taking leflunomide, the patients are recommended to discontinue leflunomide, carry out a cholestyramine washout and be referred for an appointment with an obstetrician for further monitoring. Leflunomide is not compatible with breastfeeding (1–3).
CYCLOPHOSPHAMIDE
Cyclophosphamide is a cytostatic used in rheumatology in the treatment of SLE, scleroderma (SSc), IIM and systemic vasculitis.
Cyclophosphamide has a gonadotoxic effect and before exposure to this drug it is advised to consider one of the fertility preservation procedures such as oocyte cryopreservation or the administration of gonadotropin-releasing hormone (GnRH) agonists (1).
Cyclophosphamide has proven teratogenic effects and is contraindicated in pregnancy and breastfeeding. It is advised to discontinue cyclophosphamide at least three months before a planned pregnancy (2). In exceptional cases, it can be considered in the second and third trimester in case of severe life/organ-threatening illness of the mother (1–3).
MYCOPHENOLATE MOFETIL
Mycophenolate mofetil has a cytostatic effect and it is most commonly used in rheumatology in the treatment of SLE, systemic sclerosis (SSC), IIM and systemic vasculitis.
Mycophenolate mofetil has proven teratogenic effects and it is contraindicated in pregnancy and breastfeeding in any dose. When planning a pregnancy, it is recommended to discontinue mycophenolate mofetil and replace it with a suitable drug at least six weeks in the period pre-conception in order to determine the stability of the disease. In cases of unplanned pregnancies during which the patients have been taking mycophenolate mofetil, the patients are recommended to discontinue mycophenolate mofetil, replace this drug with a drug that is compatible with pregnancy and be referred for an appointment with an obstetrician for close monitoring due to the risk of developing foetal anomalies (1–3).
JAK INHIBITORS
JAK inhibitors are tsDMARDs used in rheumatology in the treatment of RA, PsA, SpA and JIA.
Due to the small size of the molecule and expected placental transfer, as well as passage into milk, JAK inhibitors are not considered to be compatible with pregnancy and breastfeeding. JAK inhibitors have a short half-life (e.g. tofacitinib has a half-life of approximately 3 hours), but their biological effects last longer (e.g. suppression of NK cells lasts for approximately two weeks). In 2016, the EULAR gave a recommendation to discontinue tofacitinib at least two months before the planned pregnancy (3), and in 2022 the BCR recommended to discontinue JAK inhibitors at least two weeks before the planned pregnancy (1).
INTRAVENOUS IMMUNOGLOBULINS
Intravenous immunoglobulins are used, in addition to their use as replacement therapy in immunodeficiencies, as immunomodulators for the treatment of numerous inflammatory rheumatic diseases. Intravenous immunoglobulins have an important role in the treatment of antiphospholipid syndrome and immune thrombocytopenia in pregnancy and in the prevention of congenital heart block in mothers who tested positive for anti-Ro/La antibodies. Intravenous immunoglobulins are compatible with pregnancy and breastfeeding (1).
BIOLOGICS
In early pregnancy, insignificant amounts of IgG are transferred by passive diffusion, and at the end of the first trimester, only 5–10% of maternal IgG levels are measured in foetal blood samples obtained by cordocentesis (13). Active transfer of IgG occurs only between the 17th and 22nd week of pregnancy when the expression of the Fc receptor antigens in the syncytiotrophoblast begins (14). An Fc fragment is required for an active placental transfer, so formulations without the Fc domain (certolizumab pegol) have little almost no placental transfer. Most of the biologics used in rheumatology are complete monoclonal antibodies of the IgG1 subclass, while only a few are of the IgG2 and IgG4 classes (ixekizumab, an IgG4 variant, eculizumab an IgG2/IgG4 variant). The rate of placental transfer of immunoglobulin depends on the class and subclass of immunoglobulin, so IgG1 has the highest affinity for transport, followed by IgG4, IgG3 and IgG2 (15).
TNF-ALPHA INHIBITORS
The most common indications for TNF-α inhibitors in rheumatology are RA, PsA, SpA and JIA. Five TNF-α inhibitors are currently approved for clinical use (infliximab, etanercept, adalimumab, certolizumab pegol, golimumab). TNF-α has a role in organogenesis and previously there were some concerns about the risk of its use and the development of congenital abnormalities. However, numerous observational studies and data from registries indicate a good safety profile of TNF-alpha inhibitors without an increased risk of congenital malformations, spontaneous abortions or intrauterine foetal demise (16–18). Transfer of TNF-alpha inhibitors to the foetus can lead to immunosuppression and insufficient immune response to infections and vaccinations (15, 19). It is recommended to postpone live vaccines (BCG, rotavirus vaccine, measles, rubella and mumps vaccine) for 6 to 12 months after exposure to TNF-alpha inhibitors (1–3, 20).
Certolizumab is structurally an antibody fragment without the Fc domain and therefore it is showing no to minimal placental transfer. Certolizumab is suitable for use during all three trimesters of pregnancy and does not require any adjustments in the immunisation schedule of a newborn (21).
Patients with no disease activity or low disease activity who are maintaining stable treatment with the use of a TNF-alpha inhibitor with proven placental transfer (infliximab, adalimumab, golimumab, etanercept) do not need to replace this drug with certolizumab before or during pregnancy (1).
Pregnant women with a low probability of disease relapse due to discontinuation of TNF-alpha inhibitors should discontinue the following drugs: infliximab at week 20, adalimumab and golimumab at week 28, and etanercept at week 32 so that the newborn has the usual immunisation schedule (the BSR recommendation (1)). The EULAR’s recommendation is similar: to discontinue infliximab at week 20, adalimumab at week 20, etanercept at week 30–32, and a 2016 recommendation for golimumab was to discontinue this drug due to lack of evidence (3). The ACR’s recommendation is to discontinue infliximab, adalimumab, golimumab and etanercept in the third trimester, i.e. at least a few half-lives before delivery (2).
If necessary, the use of infliximab, adalimumab, golimumab, and etanercept can be continued throughout pregnancy to maintain disease control. In these cases, live vaccines should be postponed for at least six months after exposure in utero. If a TNF-α inhibitor is discontinued during pregnancy, it can be reintroduced after delivery if there are no infectious/surgical complications. Due to their low transfer rate into breast milk, all TNF-α inhibitors are considered to be compatible with breastfeeding (1–3).
ABATACEPT
Abatacept is a selective costimulation modulator used in the treatment of RA, PsA and JIA.
It is recommended to discontinue its use in case of conception/pregnancy. There is no evidence of its teratogenic effect, but there are limited safety data on its use. In case of severe maternal illness, its administration during pregnancy can be considered if there is no other compatible drug. In case of foetal exposure in the third trimester, live vaccines should be postponed for 6 months (1–3). According to the BSR recommendations, abatacept is considered to be compatible with breastfeeding.
IL-6 INHIBITORS
IL-6 inhibitors are used in the treatment of RA, JIA, adult-onset Still’s disease (AOSD) and giant cell arteritis (GCA).
It is recommended to discontinue the use of tocilizumab in case of conception/pregnancy. There is no evidence of its teratogenic effect, but there are limited safety data on its use. In case of severe maternal illness, its administration during pregnancy can be considered if there is no other compatible drug. In case of foetal exposure in the third trimester, live vaccines should be postponed for 6 months. According to the BSR recommendations tocilizumab is considered to be compatible with breastfeeding (1).
For sarilumab, the data are extremely limited, and it is only mentioned in the BSR recommendations. The BSR recommendation is the same as for tocilizumab (1).
RITUXIMAB
Rituximab is an anti-CD20 antibody that induces B-cell depletion. In rheumatology, it is indicated in RA and vasculitis, microscopic polyangiitis and granulomatosis with polyangiitis, and it also has the largest number of off-label uses.
There is no evidence of its teratogenic effect, but there are limited safety data on this drug, and it is recommended to discontinue it in the period pre-conception, i.e. during pregnancy. In some of the older recommendations it was stated that rituximab should be discontinued at least six months before conception, but since it is an IgG1 antibody whose active placental transport begins at the 16th week of pregnancy, the BSR and the ACR recommend discontinuing rituximab at conception (1, 2).
In order to maintain control over severe maternal illness, its administration during pregnancy can be considered if there is no other compatible drug. With foetal exposure in the third trimester, there is a risk of B-cell depletion, and it is recommended to postpone live vaccines until the 6th month of the infant’s life (1–3). According to the BCR and the ACR recommendations, rituximab is considered to be compatible with breastfeeding, and at the time when the EULAR’s guidelines were published, there was no sufficient evidence on this matter.
BELIMUMAB
By blocking the action of the B-lymphocyte stimulator (BLyS), belimumab reduces the number of B lymphocytes and it is the first monoclonal antibody approved for the treatment of SLE.
It is recommended to discontinue the use of belimumab in case of conception/pregnancy. There is no evidence of its teratogenic effect, but there are limited safety data on its use. In case of severe maternal illness, its administration during pregnancy can be considered if there is no other compatible drug. In case of foetal exposure in the third trimester, live vaccines should be postponed for six months. According to the BSR recommendations, belimumab is considered to be compatible with breastfeeding, and according to the ACR it is conditionally recommended, while at the time when the EULAR’s guidelines were published, there was no sufficient evidence on this matter (1, 2).
IL-1 INHIBITORS
IL-1 inhibitors are used in the treatment of periodic fever syndrome, Still’s disease in children and adults (systemic-onset juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD)) and gouty arthritis.
Anakinra is a recombinant IL-1 receptor antagonist (IL-1Ra) of high molecular mass that does not cross the placenta, while canakinumab is a human monoclonal antibody which binds to IL-1 with active placental transport from the second trimester. There is no evidence of their teratogenic effect and the exposure to IL-1 inhibitors during pregnancy is probably not harmful, however the safety data on their use are limited. The ACR and the EULAR only give recommendations for anakinra, and the BSR gives a joint recommendation for both IL-1 inhibitors. It is recommended to discontinue IL-1 inhibitors at conception/pregnancy, but their administration during pregnancy may be considered for the control of severe maternal disease if no other compatible drug is available (1–3). With foetal exposure in the third trimester, it is recommended to postpone live vaccines until after the 6th month of the infant’s life. According to the BSR recommendations, IL-1 inhibitors are considered to be compatible with breastfeeding. According to the ACR recommendations, anakinra is considered to be conditionally recommended for use during breastfeeding, and at the time when the EULAR’s guidelines were published, there was no sufficient evidence on this matter (1, 2).
IL-17 INHIBITORS
IL-17 inhibitors are used rheumatology for the treatment of SpA, PsA and JIA.
The BSR has a joint recommendation for both IL-17 inhibitors, secukinumab and ixekizumab. For IL-17 inhibitors there is no evidence of their teratogenic effect, but there are limited safety data on their use. It is recommended to discontinue the use of IL-17 inhibitors in case of conception/pregnancy. In case of severe maternal illness, its administration during pregnancy can be considered if there is no other compatible drug. In case of foetal exposure in the third trimester, live vaccines should be postponed until after the 6th month of the infant’s life (1).
When it comes to secukinumab, the ACR gives the same recommendation as the BSR, but it does not give a recommendation for ixekizumab (2). The 2016 EULAR guidelines do not state anything on IL-17 inhibitors because at that time, secukinumab (2015) and ixekizumab (2016) had just entered the market.
According to the BSR recommendations, IL-17 inhibitors are considered to be compatible with breastfeeding, and according to the ACR, secukinumab is conditionally recommended for use during breastfeeding (1, 2).
IL-12/23 INHIBITOR
The blockade of IL-12/23 is used in rheumatology for the treatment of PsA.
It is recommended to discontinue the use of ustekinumab in case of conception/pregnancy. There is no evidence of its teratogenic effect, but there are limited safety data on its use. In case of severe maternal illness, its administration during pregnancy can be considered if there is no other compatible drug. In case of foetal exposure in the third trimester, live vaccines should be postponed for after the 6th month of the infant’s life. According to the BSR recommendations ustekinumab is considered to be compatible with breastfeeding (1–3).
ANIFROLUMAB
Anifrolumab is a human IgG1 kappa monoclonal antibody that binds to the to the type I interferon receptor subunit 1 and is used in the treatment of SLE. There is still no published evidence or recommendations for the use of anifrolumab in pregnancy.
ECULIZUMAB
Eculizumab is a humanized anti-C5a monoclonal antibody of a unique IgG2/4 kappa formulation with weakened Fc function, which theoretically limits its placental transfer. Eculizumab has little to no presence in umbilical cord blood, even when used in later pregnancy, which is explained by its unique structure. In addition to its indications, paroxysmal haemolytic anaemia, atypical haemolytic uremic syndrome and generalised myasthenia gravis, eculizumab has been shown to be effective in pregnant women with refractory catastrophic antiphospholipid syndrome (C-APS) and HELLP syndrome (22). Eculizumab is a possible therapeutic option to consider for these serious conditions caused by complement activation in pregnancy. Due to insufficient safety evidence, no guidelines yet provide information on the safety of eculizumab in pregnancy (15). A summary of the compatibility of rheumatological drugs with pregnancy and breastfeeding is shown in Table 1.
PATERNAL EXPOSURE TO ANTIRHEUMATIC DRUGS
Paternal exposure to prednisone, hydroxychloroquine, methotrexate ≤ 25 mg/week, leflunomide, azathioprine, cyclosporine and tacrolimus, mycophenolate, JAK inhibitors and biologics is considered to be compatible at conception (1).
Cyclophosphamide has a gonadotoxic effect for both women and men, and before exposure to cyclophosphamide it is advised to consider one of the fertility preservation procedures such as sperm cryopreservation.
Sulfasalazine may cause reversible male infertility by causing oligospermia, reduced sperm motility and increased abnormal sperm counts (10).
CONCLUSION
Nowadays, it is mostly possible to effectively and safely treat inflammatory rheumatic diseases in pregnant women. This paper presents a summary of recent recommendations of the most relevant professional associations regarding pregnancy planning, and the application of specific pharmacological therapy used in immune-mediated inflammatory rheumatic diseases.
It is recommended to consult with your physician before conception and pregnancy planning and after achieving remission. It is recommended to replace non-compatible drugs with compatible ones in a timely manner and to use them in the minimum effective dose. In cases where there is no suitable drug that is compatible with pregnancy, the control of the mother’s severe and life-threatening disease should take priority over concerns for potentially adverse foetal outcomes. The use of all biologic drugs can be continued throughout the pregnancy if they are necessary to establish control over the activity of the mother’s severe disease. In case of exposure to a biologic drug in utero, it is necessary to adjust the immunisation schedule, i.e. postpone live vaccines for at least six months after exposure- In addition to that, longer periods of follow-up of newborns are required due to possible late effects such as the risk of malignancy and delayed immune-related events.
Acknowledgments: The authors report no acknowledgments.
Funding: For this work authors did not receive any funding.
Conflict of interest statement: The authors declare no conflict of interest.
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Table 1 Summary of drug compatibility in pregnancy and breastfeeding
Legend / legenda: ++ compatible / kompatibilan; + conditionally compatible / uvjetno kompatibilan; –– incompatible / nekompatibilan