Terapevticheskii arkhivTerapevticheskii arkhiv0040-36602309-5342LLC Obyedinennaya Redaktsiya3225010.17116/terarkh2017895105-112Review ArticleNew horizons in the use of biological agents during pregnancy in patients with rheumatic diseaseShesternyaP A-PetrovaM M-VasilyevaA O-1505201789510511210042020Copyright © 2017, Consilium Medicum2017Pregnancy in the presence of rheumatic diseases (RD) and adequate therapy before planned conception, during gestation, and after delivery during lactation is challenging. Advances in the treatment of RD are largely due to the clinical introduction of a new class of biological agents (BAs). There are less than two decades of experience in using BAs in rheumatology and to date there are no unified standards and accepted rules governing their use during pregnancy. According to the current requirements, information on a medicine should be given in three sections: 1) pregnancy; 2) lactation, and 3) use in men and women who are planning concept (the latter section has appeared for the first time). The present article summarizes data on the possible use of BAs in patients with RD during pregnancy planning, pregnancy, and breastfeeding.rheumatic diseasesrheumatoid arthritisbiological agentstumor necrosis factor inhibitorpregnancylactationbreastfeedingревматические заболеванияревматоидный артритгенно-инженерные биологические препаратыингибитор фактора некроза опухолибеременностьлактациягрудное вскармливание[Федеральные клинические рекомендации «Рематоидный артрит» 2013 года. Ссылка активна на 20.09.2016. Доступно по: http://www.rheumatolog.ru/experts/klinicheskie-rekomendacii][Насонов Е.Л., Каратеев Д.Е., Лукина Г.В. Фармакотерапия ревматоидного артрита в начале XXI века: российский и международный опыт. Тер. архив. 2013;85(8):20-28.][Chambers CD, Tutuncu ZN, Johnson D, Jones KL. Human pregnancy safety for agents used to treat rheumatoid arthritis: adequacy of available information and strategies for developing post-marketing data. Arthritis Research & Therapy. 2006;8(4):215. doi:10.1186/ar1977][Federal Register Food and Drug Administration. Rules and Regulations. Part II.21 CFR Part 201. Ссылка активна на 20.09.2016. Доступно по: https://www.gpo.gov/fdsys/pkg/FR-2014-12-04/pdf/2014-28241.pdf][Jawaheer D, Zhu JL, Nohr EA, Olsen J. Time to pregnancy among women with rheumatoid arthritis. Arthritis & Rheumatism. 2011;63(6):1517-1521. doi:10.1002/art.30327][Brouwer J, Hazes JMW, Laven JSE, Dolhain RJEM. Fertility in women with rheumatoid arthritis: influence of disease activity and medication. AnnalsoftheRheumaticDiseases. 2015;74:1836-1841. doi:10.1136/annrheumdis-2014-205383][Матьянова Е.В., Кошелева Н.М., Алекберова З.С., Александрова Е.Н. Влияние беременности на активность ревматоидного артрита и его терапию по данным проспективного наблюдения. Научно-практическая ревматология. 2015;53(3):266-273. doi:10.14412/1995-4484-2015-266-273][Mendonca LL, Khamashta MA, Nelson-Piercy C, Hughes GRV. Non-steroidal anti-inflammatory drugs as a possible cause for reversible infertility. Rheumatology (Oxford). 2000;39:880-882. doi:10.1093/rheumatology/39.8.88][Uhler ML, Hsu JW, Fisher SG, Zunaman MJ. The effect of nonsteroidal anti-inflammatory drugs on ovulation: a prospective, randomized clinical trial. Fertility and Sterility. 2001;76:957-961. doi:10.1016/S0015-0282(01)02829-1][Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG Placental Transfer in Healthy and Pathological Pregnancies. Clinical and Developmental Immunology. 2012. doi:10.1155/2012/985646][Mahadevan U, Wolf DC, Dubinsky M, Cortot A, Lee SD, Siegel CA, Ullman T, Glover S, Valentine JF, Rubin DT, Miller J, Abreu MT. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clinical Gastroenterology and Hepatology. 2013;11(3):286-292. doi:10.1016/j.cgh.2012.11.011][Skomsvoll JF, Wallenius M, Koksvik HS, Rodevand E, Salvesen KA, Spigset O, Kvien TK. Drug insight: Anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation. Nature Reviews Rheumatology. 2007;3(3):156-164. doi:10.1038/ncprheum0426][Villiger PM, Caliezi G, Cottin V, Forger F, Senn A, Ostensen M. Effects of TNF antagonists on sperm characteristics in patients
with spondyloarthritis. Annals of the Rheumatic Diseases. 2010;69(10):1842-1844. doi:10.1136/ard.2009.127423][Rezvani A, Ozaras N. Infertility improved by etanercept in ankylosing spondylitis. Indian Journal of Pharmacology. 2008;40(6):276-277. doi:10.4103/0253-7613.45155][Clowse ME, Förger F, Cush J, Wolf D, Golembesky A, Shaughnessy L, De Cuyper D, Mahadevan U. Pregnancy outcomes with trimesters of maternal exposure to certolizumab pegol: prospective and retrospective reports from safety surveillance. Annals of the Rheumatic Diseases. 2015;74(suppl.2):71. doi:10.1136/annrheumdis-2015-eular.1788][Clowse MEB, Wolf DC, Förger F, Cush JJ, Golembesky A, Shaughnessy L, Cuyper DD, Mahadevan U. Outcomes of pregnancy in subjects exposed to certolizumab pegol. The Journal of Rheumatology. 2015;42(12):2270-2278. doi:10.3899/jrheum.140189][Saougou I, Markatseli TE, Papagoras C, Kaltsonoudis E, Voulgari PV, Drosos AA. Fertility in male patients with seronegative spondyloarthropathies treated with infliximab. Joint Bone Spine. 2013;80(1):34-37. doi:10.1016/j.jbspin.2012.03.004][Viktil KK, Engeland A, Furu K. Outcomes after anti-rheumatic drug use before and during pregnancy: a cohort study among 150,000 pregnant women and expectant fathers. Scandinavian Journal of Rheumatology. 2012;41(3):196-201. doi:10.3109/03009742.2011.626442][Lee CY, Jin C, Mata AM, Tanaka T, Einarson A, Koren G. A pilot study of paternal drug exposure: the Motherisk experience. Reproductive Toxicology. 2010;29(3):353-360. doi:10.1016/j.reprotox.2010.01.00][Satoa A, Naganumaa M, Asakurab K, Nishiwakib Y, Yajimaa T, Hisamatsua T, Iwaoa Yi, Takebayashib T, Watanabec M, Hibia T. Conception outcomes and opinions about pregnancy for men with inflammatory bowel disease. Journal of Crohn’s and Colitis. 2010; 4:183-188. doi:10.1016/j.crohns.2009.10.004][Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011;117(5):1499-1506. doi:10.1182/blood-2010-07-295444][Kuriya B, Hernández-Díaz S, Liu J, Bermas BL, Daniel G, Solomon DH. Patterns of medication use during pregnancy in rheumatoid arthritis. Arthritis Care & Research (Hoboken). 2011;63(5):721-728. doi:10.1002/acr.20422][Pendergraft WF, McGrath MM, Murphy AP, Murphy P, Laliberte KA, Greene MF, Niles JL. Fetal outcomes after rituximab exposure in women with autoimmune vasculitis. Annals of the Rheumatic Diseases. 2013;72(12):2051-2053. doi:10.1136/annrheumdis-2013-203833][Rubbert-Roth A, Goupille P M, Moosavi S, Hou A. First experiences with pregnancies in RA patients receiving tocilizumab therapy. Arthritis & Rheumatism. 2010;62(suppl.10):384. doi:10.1002/art.28153][Zaretsky MV, Alexander JM, Byrd W, Bawdon RE. Transfer of inflammatory cytokines across the placenta. Obstetrics & Gynecology. 2004;103(3):546-550.][Fischer-Betz R, Specker C, Schneider M. Successful outcome of two pregnancies in patients with adult-onset Still’s disease treated with IL-1 receptor antagonist (anakinra). Clinical and Experimental Rheumatology. 2011;29(6):1021-1023.][Berger CT, Recher M, Steiner U, Hauser TM. A patient’s wish: anakinra in pregnancy. Annals of the Rheumatic Diseases. 2009; 68:1794-1795. doi:10.1136/ard.2008.105833][Ojeda-Uribe M, Afif N, Dahan E, Sparsa L, Haby C, Sibilia J, Ternant D, Ardizzone M. Exposure to abatacept or rituximab in the first trimester of pregnancy in three women with autoimmune diseases. Clinical Rheumatology. 2013;32(5):695-700. doi:10.1007/s10067-012-2156-4][Pham T, Bachelez H, Berthelot JM, Blacher J, Claudepierre P et al. Abatacept therapy and safety management. Joint Bone Spine. 2012;79(suppl.1):3-84. doi:10.1016/S1297-319X(12)70011-8][Ostensen M, Fuhrer L, Mathieu R, Seitz M, Villiger P M. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Annals of the Rheumatic Diseases. 2004;63:1212-1217. doi:10.1136/ard.2003.016881][Hazes JMW, Coulie PG, Geenen V, Vermeire S, Carbonnel F, Louis E, Masson P, Keyser FD. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use. Rheumatology. 2011;50(11):1955-1968. doi:10.1093/rheumatology/ker302][Man YA, Bakker-Jonges LE, Dufour-van den Goorbergh CM, Tillemans SPR, Hooijkaas H, Hazes JMW, Dolhain RJEM. Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy. Annals of the Rheumatic Diseases. 2010;69:420-423. doi:10.1136/ard.2008.104331][Кошелева Н.М., Матьянова Е.В. Ревматоидный артрит и беременность. Научно-практическаяревматология. 2014;52 (6):589-599. doi:10.14412/1995-4484-2014-589-599][Lin HC, Chen SF, Lin HC, Chen YH. Increased risk of adverse pregnancy outcomes in women with rheumatoid arthritis: a nationwide population-based study. Annals of the Rheumatic Diseases. 2010;69(4):715-717. doi:10.1136/ard.2008.105262.][Jakobsson GL, Stephansson O, Askling J, Jacobsson LTH. Pregnancy outcomes in patients with ankylosing spondylitis: a nationwide register study. Annals of the Rheumatic Diseases. 2016;75:1838-1842. doi:10.1136/annrheumdis-2015-207992][Rom AL, Wu CS, Olsen J, Kjærgaard H, Jawaheer D, Hetland ML, Vestergaard M, Mоrch LS. Fetal Growth and Preterm Birth in Children Exposed to Maternal or Paternal Rheumatoid Arthritis: A Nationwide Cohort Study. Arthritis & Rheumatology. 2014; 66(12):3265-3273. doi:10.1002/art.38874][Steenwinkel FDO, Hokken-Koelega ACS, Man YA, Rijke YB, Ridder MAJ, Hazes JMW, Dolhain RJEM. Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2013;72:1995-2001. doi:10.1136/annrheumdis-2012-202539][Шилкина Н.П., Бутусова С.В. Эндотелиальная дисфункция у больных ревматического профиля. Клиническаямедицина. 2013;91(4):58-61.][Verstappen SMM, King Y, Watson KD, Symmons DPM, Hyrich KL, BSRBR Control Centre Consortium, BSR Biologics Register. Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register. Annals of the Rheumatic Diseases. 2011;70:823-826. doi:10.1136/ard.2010.140822][Marchioni RM, Lichtenstein GR. Tumor necrosis factor-α inhibitor therapy and fetal risk: A systematic literature review. World Journal of Gastroenterology. 2013;19(17):2591-2602. doi:10.3748/wjg.v19.i17.2591][Clowse MEB. The use of anti-TNFα medications for rheumatologic disease in pregnancy. International Journal of Womens Health. 2010;2:199-209. doi:10.2147/ijwh.s6029][Carter JD, Ladhani A, Ricca LR, Valeriano J, Vasey FB. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. The Journal of Rheumatology. 2009;36(3):635-641. doi:10.3899/jrheum.080545][Koren G. Do Tumor Necrosis Factor Inhibitors Cause Malformations in Humans? The Journal of Rheumatology. 2009;36(3):465-466. doi:10.3899/jrheum.081083][Hyrich KL, Verstappen SMM. Biologic therapies and pregnancy: the story so far. Rheumatology. 2014;53(8):1377-1385. doi:10.1093/rheumatology/ket409][Ben-Horin S, Yavzori M, Kopylov U, Picard O, Fudim E, Eliakim R, Chowers Y, Lang A. Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease. Journal of Crohn’s and Colitis. 2011;5(6):555-558. doi:10.1016/j.crohns.2011.05.006][Berthelsen BG, Fjeldsoe-Nielsen H, Nielsen CT, Hellmuth E. Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding. Rheumatology. 2010;49(11):2225-2227. doi:10.1093/rheumatology/keq185][Fritzsche J, Pilch A, Mury D, Schaefer C, Weber- Schoendorfer C. Infliximab and adalimumab use during breastfeeding. Journal of Clinical Gastroenterology. 2012;46(8):718-719. doi:10.1097/MCG.0b013e31825f2807][Keeling SG, Wolbink J. Measuring multiple etanercept levels in the breast milk of a nursing mother with rheumatoid arthritis. The Journal of Rheumatology. 2010;37(7):1551. doi:10.3899/jrheum.100077][Horst S, Kane S. The use of biologic agents in pregnancy and breastfeeding. Gastroenterology Clinics of North America. 2014;43(3):495-508. doi:10.1016/j.gtc.2014.05.005][Nguyen GC, Seow CH, Maxwell C3, Huang V, Leung Y, Jones J, Leontiadis GI, Tse F, Mahadevan U, van der Woude CJ; IBD in Pregnancy Consensus Group. The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. Gastroenterology. 2016;150(3):734-757. doi:10.1053/j.gastro.2015.12.003][Gotestam Skorpen C, Hoeltzenbein M, Tincani A. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Annals of the Rheumatic Diseases. 2016;75:795-810. doi:10.1136/annrheumdis-2015-208840][Flint J, Panchal S, Hurrell A, Venne M, Gayed M, Schreiber K, Arthanari S, Cunningham J, Flanders L, Moore L, Crossley A, Purushotham N, Desai A, Piper M, Nisar M, Khamashta M, Williams D, Gordon C, Giles I. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology. 2016. doi:10.1093/rheumatology/kev404]