eMedicine Specialties > Rheumatology > Rheumatoid Arthritis
Rheumatoid Arthritis and Pregnancy: Treatment & Medication
Updated: Jun 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Preconception counseling
- It is important to counsel patients about the teratogenicity and adverse effects of the medications used to treat rheumatoid arthritis (RA) before starting therapy. Patients may need a reminder about the importance of using contraception during DMARD therapy, especially methotrexate, leflunomide, and cyclophosphamide.
- Educate patients that, because of a prolonged half-life, some of these medications may need to be discontinued several months before conception is planned.
- In addition to discontinuation, some patients who take DMARDs may require treatment with other medications to enhance their clearance.
Surgical Care
- Cesarean delivery does not appear to be performed more commonly in patients with RA.
Consultations
- Obstetrician and gynecologist: Work closely with the rheumatologist, especially if patients are on disease-modifying agents or steroids.
- Ophthalmologist: Patients on hydroxychloroquine may need an eye examination to assess for drug toxicity.
Diet
- A low-fat, high-carbohydrate, high-fiber diet is recommended in pregnant patients with RA. Fish oils in moderate quantities can be taken during pregnancy.
- Over-the-counter herbal remedies should probably be avoided.
- Calcium supplementation is recommended to prevent osteoporosis.
Activity
Strenuous activity is best avoided in patients who experience RA flare-ups. Physical and occupational therapy can be beneficial in patients with RA.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
None of the medications used in the treatment of arthritis is absolutely safe during pregnancy. Hence, the decision to use medications should be made after careful assessment of the risks and benefits in consultation with the patient. Pain control through nonpharmacologic management (eg, paraffin baths, decreased physical activity, splinting, cold packs) can be used as adjunctive care.
Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) should be stopped at the beginning of a menstrual cycle when conception is planned, as NSAIDs have been shown to interfere with blastocyst implantation in animal studies. Most traditional NSAIDs are considered Category B medications but should be used with caution in pregnancy.18 Possible effects on the mother include prolonged gestation and labor, increased peripartum blood loss, and increased anemia. The potential adverse effects in the fetus include impaired fetal renal function with oligohydramnios and increased cutaneous and intracranial bleeding. Monitoring for oligohydramnios should be considered if the pregnant patient is on prolonged NSAID therapy.
NSAIDs are contraindicated in the third trimester, as they promote premature closure of the ductus arteriosus, leading to fetal pulmonary hypertension. Ductal constriction can occur at any gestational age; however, one study noted a dramatic increase in indomethacin-induced ductal constriction at 31 weeks’ gestation.19 Stopping NSAID therapy prior to 31 weeks’ gestational age is prudent for potentially avoiding adverse effects in the fetus. Short-acting NSAIDs (eg, ibuprofen, indomethacin, diclofenac) are preferred over long-acting agents.
Cyclooxygenase-2 (COX-2) inhibitors are generally considered Category C medications and potentially share the same side effects as traditional NSAIDs.
Corticosteroids
Corticosteroids are potent anti-inflammatory agents. They are considered relatively safe in pregnancy when used in low doses (ie, <20 mg) and are considered Category B medications. Nonetheless, they may increase the maternal risk of hypertension, edema, gestational diabetes, osteoporosis, premature rupture of membranes, and small-for-gestational-age babies. One meta-analysis found a 3.5-fold increase in risk of cleft palate in fetuses with first-trimester exposure to corticosteroids.20
The choice of glucocorticoid depends on whether the mother or the fetus needs to be treated. Hydrocortisone and cortisone cross the placenta, but 11 beta-dehydrogenase, a placental enzyme, converts hydrocortisone to cortisone, which is biologically inactive; thus, the fetus is exposed to only approximately 10% of the maternal dose.21 Therefore, if steroid treatment is desired for the mother, hydrocortisone, cortisone, or prednisone should be chosen. Dexamethasone and betamethasone cross the placenta with similar maternal and fetal concentrations; thus, they are the treatment of choice for fetal respiratory distress.
The lowest possible steroid dose needed to control activity should be used in pregnancy. Routine oral calcium and vitamin D supplementation is recommended. Stress doses of steroids should be used during labor and delivery if the mother received steroids (even low-dose) for more than 2-3 weeks during pregnancy, and the neonate should be monitored for evidence of adrenal insufficiency and infection.
Disease-modifying antirheumatic drugs
Methotrexate, a folic acid antagonist, is contraindicated in pregnancy (Category X medication) because it is an abortifacient and has teratogenic effects, including craniofacial abnormalities, limb defects, and CNS defects such as anencephaly, hydrocephaly, and meningomyelopathy, especially with first-trimester exposure.18 Because the active metabolites have a long half-life, methotrexate must be discontinued at least 3 months prior to conception; treatment with folic acid should be continued in that period and throughout pregnancy.
Leflunomide, a pyrimidine synthesis inhibitor, is also a Category X medication, and is extremely teratogenic and absolutely contraindicated in pregnancy. Its half-life is 14-15 days, but the active metabolite undergoes extensive enterohepatic circulation; thus, the drug takes up to 2 years to be undetectable in plasma. Therefore, discontinuation of the drug before conception is insufficient. The drug needs to be eliminated with administration of cholestyramine 8 g 3 times daily for 11 days. Plasma levels of less than 0.02 mg/L should be verified with 2 separate tests at least 2 weeks apart.22 If unacceptably high levels persist, additional cholestyramine maybe given.
Sulfasalazine, a dihydrofolate reductase inhibitor, is a Category B medication. Sulfasalazine does not increase fetal morbidity or mortality and is considered safe in pregnancy.23
Azathioprine, although a Category D medication, can be used if the benefits outweigh the risks. Although fewer women who received azathioprine for renal transplantation completed their pregnancies, no increase in fetal anomalies was observed. Azathioprine crosses the placenta, but the fetal liver lacks the enzyme inosinate pyrophosphorylase, which converts azathioprine to its active metabolite, 6-mercaptopurine; thus, the fetus is protected from the agent's teratogenic effects.18 A retrospective cohort study of 155 patients found no statistical difference in conception failures, abortion secondary to a birth defect, major congenital malformations, neoplasia, or increased infections among patients taking 6-mercaptopurine compared with controls.24 A study of 101 pregnancies of women with inflammatory bowel disease on azathioprine at doses of 100 mg/day revealed no association with poor pregnancy outcomes.25
Hydroxychloroquine, an antimalarial agent, is considered a Category C medication. Previous reports of fetal toxicity with hydroxychloroquine were based on effects of chloroquine, which has 2.5 times the amount of tissue deposition as hydroxychloroquine. No real fetal toxicity is associated with hydroxychloroquine at the dosage used for rheumatoid arthritis (RA) and connective-tissue disease (6.5 mg/kg body weight).26 Several studies and case series have provided further evidence that no fetal toxicity was associated with hydroxychloroquine therapy in mothers.27,28,29
Biologic agents
Biologic agents are now commonly used for the treatment of RA; however, limited data are available on their use in pregnancy.
Medications in the anti-TNF-alpha class (ie, currently, etanercept, adalimumab, and infliximab) are commonly used in the treatment of RA. They have been labeled by the FDA as Class B medications, as no adequate human studies have shown risk, but animal studies have shown no harm done to the fetus.1,30 Thus far, no randomized, blinded, placebo-controlled trials have been completed to demonstrate any potential teratogenicity. Numerous case reports have show positive outcomes with anti-TNF-alpha use in pregnancy, with an incidence of spontaneous abortion and birth defects similar to that in the general population.2,3,4,5,31,32,33,34 Compared with healthy controls, the risk of preterm delivery and poor growth of offspring in all patients with RA is increased, but this is believed to be more attributable to the underlying systemic disease rather than to use of TNF blockers.35,6
The Organization of Teratology and Information Specialist (OTIS) Project is the largest prospective cohort study to date evaluating anti-TNF-alpha medications and other medications used to treat autoimmune disease. This study, led by the University of California at San Diego, is maintaining a database of patients taking etanercept and adalimumab during first-trimester gestation.
The results for adalimumab have been updated and analyzed to May 2008. So far in this group, 30 patients have been enrolled,36 with an additional retrospective case series involving 66 patients whose outcomes have been monitored. Based on preliminary data, no concerns have been raised regarding the risks of adverse outcomes with adalimumab exposure, and rates of congenital defects are in range of the general population. As of October 2006, 48 pregnant patients had been enrolled and received treatment in the OTIS etanercept prospective cohort study. Based on preliminary data from this ongoing study, no concerns have been raised or consistent abnormalities found.8,37 Because of the small sample size, no definitive conclusions about adalimumab or etanercept can be made at this time.
Rituximab (Rituxan), a monoclonal antibody that inhibits CD20 antigen on B lymphocytes, is currently a Pregnancy Category C medication. Rituximab is indicated for the treatment for moderate to severe RA.38 Case reports on the use of rituximab during pregnancy have been reported in the oncology literature.39,40,41,42 Case reports have also shown that rituximab therapy results in detectable levels of the drug in cord blood and results in B-cell depletion in both mother and neonate.43,44 Recovery of B-cell levels in the neonate has been reported to occur at age 3-4 months and does not appear to impair antibody formation to immunizations.43,44 The dosing of rituximab in case reports was 375 mg/m2 in 1-6 cycles.44,39 Although it is unknown whether rituximab is excreted in human milk, IgG is present in human milk, and rituximab has been detected in the milk of monkeys.38Immunomodulators
Anakinra (Kineret), an interleukin-1 receptor antagonist, is used to treat severe RA. No studies or case reports using this medication during human pregnancy or lactation were found in the literature nor reported in data provided by the drug manufacturer. Anakinra is a Pregnancy Category B medication. No adverse effects have been reported in rats and rabbits receiving up to 100 times the recommended human dose. No data are available to indicate whether anakinra is excreted in human milk.45
Abatacept (Orencia) is a selective costimulation modulator that binds to CD80 and CD86, thereby inhibiting activation of T lymphocytes and interactions with CD28. Abatacept is indicated for the treatment of moderate to severe RA.46 No human studies have investigated the use of this medication during pregnancy or lactation. Similarly, no case reports have described abatacept therapy in human pregnancy or lactation in the literature or in drug company records.
Abatacept, which is a Pregnancy Category C medication, has been found to cross the placenta and be excreted in rat milk. No teratogenic effects were reported in mice or rabbits treated with a dose 29 times greater than that recommended for humans. Similarly, no adverse effects in offspring were reported when rats were treated with 3 times the human dose throughout the lactation period. In a sample of 20 rats (10 male, 10 female) treated with 11 times the human dose of abatacept, one female offspring had an increased response of T-cell–dependent antibodies and experienced thyroid inflammation.46
Nonsteroidal anti-inflammatory drugs
These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is unknown, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may include inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.
Ibuprofen (Motrin, Advil)
DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. Lowest effective dose is prescribed prn. Treatment is stopped 6-8 wk prior to delivery.
Adult
400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; start at lower end of dosing range and titrate; not to exceed 3.2 g/d
Pediatric
20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
Celecoxib (Celebrex)
Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose for each patient. No experience exists with use in pregnant women. Teratogenic effects have been observed in animals on high doses. Causes an increase in embryo loss in rats. Use is justified only if potential benefit outweighs risk.
Adult
200 mg/d PO qd; alternatively, 100 mg PO bid; use lowest effective dose
Pediatric
Not established
Coadministration with fluconazole may cause increase in plasma concentrations because of inhibition of celecoxib metabolism; coadministration with rifampin may decrease plasma concentrations; may decrease antihypertensive effect of ACE inhibitors; may decrease natriuretic effect of furosemide and thiazides
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, conditions predisposing to fluid retention, severe heart failure, and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate symptoms and signs suggesting liver dysfunction or with abnormal liver lab results; may cause renal failure
Indomethacin (Indocin)
Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.
Adult
25-50 mg PO bid/tid; 75 mg SR PO bid; not to exceed 200 mg/d
Pediatric
1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; GI bleeding or renal insufficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur, discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia is present
Aspirin (Anacin, Ascriptin, Bayer Aspirin)
Treats mild to moderate pain at high doses. Inhibits prostaglandin synthesis, which, in turn, may inhibit pain and inflammation.
Also inhibits platelet aggregation and is used in low doses as an anticoagulant in prothrombotic conditions such as antiphospholipid antibody syndrome
Adult
4 g/d PO in divided doses (take with fluids)
Pediatric
Individualize dosing; suggested dosing is 10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; because of the association of aspirin with Reye syndrome, do not use in children (<16 y) with viral infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, patients with history of blood coagulation defects, or patients taking anticoagulants
Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Sterapred)
May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. If steroid treatment is desired for the mother, prednisone, cortisone, or hydrocortisone should be chosen, as very low concentration of the active steroid reaches the fetus.
Adult
5-20 mg/d PO qd; lowest effective dose is prescribed
Pediatric
0.05-2 mg/kg/d PO divided tid/qid
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; may alter levels of warfarin
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; high doses may result in growth retardation and cleft palate in fetus; if used during pregnancy, newborn must be monitored for adrenal suppression and infection
Methylprednisolone (Medrol, Solu-Medrol)
Decreases inflammation by suppressing migration of PMN leukocytes and reversing increased capillary permeability. Metabolized by placenta, and lesser concentrations are available for the fetus. Therefore, preparation preferred.
Adult
5-20 mg/d PO qd; lowest effective dose is prescribed
Pediatric
0.5-1.7 mg/kg/d or 5-25 mg/m2/d PO divided bid/qid
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; high doses may result in growth retardation of fetus; cleft palate has been observed in animals; if used during pregnancy, newborn must be monitored for adrenal suppression and infection
Disease-modifying antirheumatic agents
Potential benefit of use should outweigh risks. Slow onset of these agents must be considered before use during pregnancy. Effects can last for months, and decision to stop must be made before conception.
Sulfasalazine (Azulfidine)
The precise action of sulfasalazine or its metabolites (ie, 5-aminosalicyclic acid [5-ASA], sulfapyridine) may be related to anti-inflammatory or immunomodulatory properties. It is used for RA in patients who have had an inadequate response to salicylates or other NSAIDs. Also used for patients with polyarticular-course juvenile RA who have responded inadequately to salicylates or other NSAIDs.
Preferred DMARD during pregnancy. No increase in fetal morbidity was observed following its use during pregnancy in patients with inflammatory bowel disease.
Adult
2-3 g PO divided tid/qid
Pediatric
<6 years: Not established
>6 years: 30-50 mg/kg/d PO divided bid; begin with 1/4 to 1/3 of expected maintenance dose, initially; may increase weekly maximum to 2 g/d
Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate; inhibits absorption of folic acid (folate supplementation recommended by some clinicians)
Documented hypersensitivity; GI or GU obstruction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction; may precipitate acute attack of porphyria
Hydroxychloroquine (Plaquenil)
Inhibits chemotaxis of eosinophils and locomotion of neutrophils. Impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate at 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.
Adult
200-400 mg/d PO in divided doses
Pediatric
Not established
Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption
Documented hypersensitivity; psoriasis; retinal and visual-field changes attributable to 4-aminoquinolones
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; perform periodic (eg, 6 mo) ophthalmologic examinations; test periodically for muscle weakness
Azathioprine (Imuran)
A purine analog that antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. In RA, it decreases the circulating B and T lymphocytes, immunoglobulin synthesis, and cytokine production. May be needed for arthritis resistant to conventional DMARDS or for extraarticular rheumatoid manifestations.
Adult
1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d
Pediatric
Not established
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity to azathioprine or any component of the formulation
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution in liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and monitor liver, renal, and hematologic function; pancreatitis rarely associated
Biologic response modifiers
These newly engineered and specifically targeted biopharmaceutical agents target cellular subsets, adhesion molecules, T-cell receptors, class 2 major histocompatibility complex (MHC), and various cytokines.
Anakinra (Kineret)
Competitively and selectively inhibits interleukin-1 (IL-1) binding to type I receptor (IL-1RI). IL-1 is found in excess in patients with RA and is produced in response to inflammatory stimuli. By blocking IL-1 binding, inflammation and pain associated with RA are inhibited. Indicated for moderate-to-severe RA in patients whose conditions have failed one or more DMARDs. Dose should be administered at approximately the same time every day.
Adult
100 mg SC qd
Pediatric
Not established
None reported; higher rate of serious infections and neutropenia are possible when coadministered with TNF blocking agents (eg, etanercept, infliximab, adalimumab); may decrease response to live-virus vaccines
Documented hypersensitivity to product or E coli –derived products; active infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Serious infections may occur (discontinue treatment if serious infection develops); neutropenia may occur (especially if administered concomitantly with TNF blocking agents); most common adverse effect is local reaction at site of injection; caution if administered to nursing women
Tumor Necrosis Factor Inhibitors
TNF-a is a cytokine that plays a significant role in producing proinflammatory effects in RA. The biologic agents directed against TNF-a have been very successful in treating RA by decreasing inflammatory and immune responses.
Etanercept (Enbrel)
Soluble p75 TNF receptor fusion protein (sTNFR-Ig). Inhibits TNF binding to cell surface receptors, which, in turn, decreases inflammatory and immune responses.
Adult
25 mg SC 2 times/wk with or without concomitant administration of MTX
Pediatric
Not established
Do not administer within 3 mo of live virus vaccines (eg, MMR)
Documented hypersensitivity; sepsis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Increases risk of serious infections, including infections that may result in hospitalization or death; may increase risk of opportunistic infections (eg, tuberculosis [TB], invasive fungal), if serious infections develop, discontinued therapy; possible adverse effects include injection site pain, redness and swelling at injection site, and headaches; rare cases of lupus-like symptoms and heart failure have been reported (discontinue treatment if symptoms develop)
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-a and inhibits its binding to TNF-a receptor. Reduces infiltration of inflammatory cells and TNF-a production in inflamed areas. Used with methotrexate in patients that have had inadequate response to methotrexate monotherapy.
Adult
3 mg/kg IV (in combination with methotrexate therapy); follow by additional 3 mg/kg at 2 and 6 wk after first dose; repeat q8wk thereafter
Pediatric
Not established
None reported
Documented hypersensitivity; sepsis; concurrent live vaccination; active infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Anti-TNF therapies may adversely affect normal immune responses and allow development of superinfections; may increase risk of reactivation of tuberculosis; discontinue if serious infection develops; associated with CNS demyelination (rare); autoantibody development may occur, causing lupuslike syndrome; more cases of lymphoma were observed in TNF-a blockers compared with controlled groups; injection site pain, redness, and swelling at injection site with Enbrel and Humira (SC administration)
Rituximab (Rituxan)
A chimeric monoclonal antibody directed against the CD20 antigen on B-lymphocytes that leads to their depletion. Has shown success in refractory RA and other connective-tissue diseases in recent small pilot studies. RA, previously believed to be a TH-1–mediated disease, is now emerging as a more diverse disease immunopathologically. B lymphocytes, primarily considered to be mere sources of autoantibody production, have shown an important role in antigen presentation to T cells and other proinflammatory processes, including cytokine production.
Currently, rituximab is FDA-approved only for the treatment of non-Hodgkin lymphoma.
Adult
Course of 2 IV infusions 1000 mg/infusion given 2 wk apart
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypotension, bronchospasm, and angioedema may occur; discontinue treatment if life-threatening cardiac arrhythmias occur
Adalimumab (Humira)
Recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. Reserved for those who experience inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). Can be used alone or in combination with methotrexate (MTX) or other DMARDs. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.
Adult
40 mg SC q2wk; may increase to 40 mg SC qwk in some patients not receiving concomitant MTX
Pediatric
Not established
May interfere with immune response to live virus vaccine (eg, MMR) and reduce efficacy; methotrexate (MTX) decreases clearance (available data do not support adjusting dose of either adalimumab or MTX); coadministration with anakinra (an interleukin-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections
Documented hypersensitivity; active infection
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Causes immunosuppression; may be associated with serious infections (some fatal) including reactivation of tuberculosis, sepsis, or opportunistic infections, discontinue if serious infection occurs; increases risk for lymphoma development; associated with CNS demyelination (rare); autoantibody development may occur causing lupus-like syndrome; may cause hypersensitivity reactions including anaphylaxis and hematologic adverse effects (ie, pancytopenia, aplastic anemia); exacerbation of CHF or new onset CHF has been observed with TNF-blocking agents
More on Rheumatoid Arthritis and Pregnancy |
| Overview: Rheumatoid Arthritis and Pregnancy |
| Differential Diagnoses & Workup: Rheumatoid Arthritis and Pregnancy |
 Treatment & Medication: Rheumatoid Arthritis and Pregnancy |
| Follow-up: Rheumatoid Arthritis and Pregnancy |
| References |
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Further Reading
Keywords
rheumatoid arthritis and pregnancy, RA, arthritis, DMARDs and pregnancy, disease-modifying anti-rheumatic drugs, disease-modifying antirheumatic drugs, spontaneous abortions, preeclampsia, preterm delivery, pregnancy complications, pregnancy management, adverse fetal outcome, decreased sexual drive, ovulation dysfunction, impaired hypothalamic-pituitary-adrenal axis, impaired HPA axis
