DOI: https://dx.doi.org/10.18203/2320-1770.ijrcog20163402
Published: 2016-12-15

Current understanding of rheumatoid arthritis therapy in pregnancy

Sujata Swain, Paresh Jena

Abstract


Pregnancy in most cases is associated with remission of rheumatoid arthritis (RA), but a quarter of patients continue to have active disease or even worsening of the disease and most patients who improve, relapse in the postpartum period. Patients with RA do not have decreased fertility. A majority of patients with RA may go in remission, but patients who continue with the disease activity require treatment. Drugs that may be safely used during pregnancy include NSAIDs except in third trimester, corticosteroids as low dose prednisone. The preferred disease-modifying agents (DMARDs), during pregnancy are sulfasalazine and hydroxychloroquine. Azathioprine and cyclosporine can be used if the benefits outweigh the risks. Methotrexate and lefunomide are contraindicated and must be prophylactically withdrawn before a planned pregnancy. Biologics like anti-TNF agents, rituximab and abatacept generally should be stopped when pregnancy is discovered. An overall rational approach is highly warranted to treat RA during pregnancy.


Keywords


Biologics, DMARDs, Disease activity, Oligohydramnios, Rheumatoid arthritis, Remission, Teratogenic

Full Text:

PDF

References


Katz PP. Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheu. 2006;54:899-907.

Kraaimaat FW, Bakker AH, Janssen E, Bijlsma JW. Intrusiveness of rheumatoid arthritis on sexuality in male and female patients living with a spouse. Arthritis Care Res. 1996;9(2):120-5.

Flaiser F, Heden B, Sany J, Combe B. A study of ovarian function in rheumatoid arthritis. Rev Rheum. 1995;62:549-54.

Wallenius M, Skomsvoll JE, Irgens LM. Pregnancy and delivery in women with chronic inflammatory arthritis with specific focus on birth order. Arthritis Rheum. 2011;60:1534-42.

Man YA, Hazes JMW, Heide VH. Association of higher rheumatoid arthritis disease activity during pregnancy with lower birth weight. Arthritis Rheum. 2009;60:3196-206.

Bowden AP, Barrett JH, Fallow W, Silman AJ. Women with inflammatory poly arthritis have babies of lower birth weight. J Rheumatology. 2001;28:355-9.

Ostensen M, Aune B, Husby G. Effect of pregnancy and hormonal changes on the activity of rheumatoid arthritis. Scand J Rheumatology. 1983;12:69-72.

Nelson JL, Hughes KA, Smith AG. Maternal and fetal disparity in HLA class II alloantigens and the pregnancy induced ameloriation of rheumatoid arthritis. N Engl J Med. 1993;329:466-71.

Man YA, Dolhain RJ, Geijn FE. Disease activity of rheumatoid arthritis during pregnancy results from nation-wide prospective study. Arthritis Rheum. 2008;59:1241-8.

Elenkov IJ, Wilder RL, Bakalov VK, et al. IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times. J Clin Endocrinol Metab. 2001;86:4933-8.

Tibbetts TA, DeMayo F, Rich S, Conneely OM, Malley BW. Progesterone receptors in the thymus are required for thymic involution during pregnancy and for normal fertility. Proc Natl Acad Sci USA. 1999;96:12021-6.

Rango U. Fetal tolerance in human pregnancy a crucial balance between acceptance and limitation of trophoblast invasion. Immunol Lett. 2008;115:21-32.

Forger F, Marcoli N, Gadola S, Moller B, Villiger PM, Ostensen M. Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:984-90.

Kahn DA, Baltimore D. Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance. Proc Natl Acad Sci. 2010;107:9299-304.

Whitacre CC. A gender gap in autoimmunity. Science. 1999;283:1277-8.

Zoli A, Lizzio MM, Ferlisi EM, Massafra V, Mirone L, Barini A, et al. ACTH, cortisol and prolactin in active rheumatoid arthritis. Clin Rheumatol. 2002;21(4):289-93.

Ostenen M, Lockshin M, Doria A. Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatology. 2008;47(3):28-31.

18. Vermillion ST, Scardo JA, Lashus AG, Wiles HB. The effect of indomethacin tocolysis on fetal ductus arteriosus constriction with advancing gestational age. Am J Obstet Gynecol. 1997;177(2):256-9.

Temprano KK, Bandlamudi R, Moore TL. Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum. 2005;35(2):112-21.

Chambers CD, Johnson DL, Robinson LK. Organisation of teratology information specialists collaborative research group birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum. 2010;62:1494-503.

Mogadam M, Dobbins WO, Korelitz BI, Ahmed SW. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology. 1981;80(1):72-6.

Parke A, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol. 1996;23(10):1715-8.

Buchanan NM, Toubi E, Khamashta MA, Lima F, Kerslake S, Hughes GR. Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases. Ann Rheum Dis. 1996;55(7):486-8.

Costedoat CN, Amoura Z, Duhaut P, Huong DL, Sebbough D, Wechsler B, et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum. 2003;48(11):3207-11.

Motta M, Tincani A, Faden D, Zinzini E, Chirico G. Antimalarial agents in pregnancy. Lancet. 2002;359(9305):524-5.

Barrett JH, Brennan P, Fiddler M, Silman AJ. Does rheumatoid arthritis remit during pregnancy and relapse postpartum? results from a nationwide study in the United Kingdom performed prospectively from late pregnancy. Arthritis Rheum. 1999;42(6):1219-27.

Treacy G. Using an analogous monoclonal antibody to evaluate the reproductive and chronic toxicity potential for a humanized anti-TNFalpha monoclonal antibody. Hum Exp Toxicol. 2000;19(4):226-8.

Clowse ME. The use of anti TNF╬▒ medications for rheumatologic disease in pregnancy. Int J Women Health. 2010;2:199-209.

Klink DT, Elburg RM, Schreurs MW, Well GT. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol. 2008;2008:271363.

Ostensen M, Forger F. Treatment with biologics of pregnant patients with rheumatic diseases. Curr Opin Rheumatol. 2011;23(3):293-8.

Use of orencia during pregnancy and effects on fertility, personal communication with Kelly S. Park, PharmD, MBA, representative of Bristol-Myers Squibb.: Bristol-Myers Squibb. 2008.

Johns DG, Rutherford LD, Leighton PC, Vogel CL. Secretion of methotrexate into human milk. Am J Obstet Gynecol. 1972;112(7):978-80.

EBPG expert group on renal transplantation. European best practice guidelines for renal transplantation. Long-term management of the transplant recipient. Pregnancy in renal transplant recipients. Nephrol Dial Transplant. 2002;17(4):50-5.

American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics. 1994;93(1):137-50.

Kane S, Ford J, Cohen R, Wagner C. Absence of infliximab in infants and breast milk from nursing mothers receiving therapy for Crohn's disease before and after delivery. J Clin Gastroenterol. 2009;43(7):613-6.