MEDICAMENTOS INMUNOSUPRESORES Y BIOLÓGICOS EN EMBARAZO, LACTANCIA Y FERTILIDAD EN ENFERMEDADES INMUNOMEDIADAS

Olatz Ibarra Barrueta; Estela García Martín; Piedad López Sánchez; Esther Ramírez Herráiz; Vicente Merino Bohórquez; Arantza Ais Larisgoitia

MEDICAMENTOS INMUNOSUPRESORES Y BIOLÓGICOS EN EMBARAZO, LACTANCIA Y FERTILIDAD EN ENFERMEDADES INMUNOMEDIADAS

Olatz Ibarra Barrueta, Estela García Martín, Piedad López Sánchez, Esther Ramírez Herráiz, Vicente Merino Bohórquez, Arantza Ais Larisgoitia

Resumen

Objetivo: El objetivo de esta revisión es reunir los datos disponibles de los diferentes medicamentos utilizados en las enfermedades inflamatorias inmunomediadas en la gestación, lactancia, su influencia en la fertilidad femenina y masculina, consejos sobre suspensión antes de la concepción y servir de ayuda en la práctica clínica habitual para un mejor consejo al paciente en la planificación familiar.

Métodos: Se realizó una búsqueda bibliográfica, donde se seleccionaron los artículos publicados (estudios de revisión, observacionales y series de casos) en lengua inglesa o española hasta abril de 2020 que analizaban el manejo del embarazo, lactancia y/o fertilidad en pacientes con tratamientos utilizados en las IMID de dermatología, reumatología y digestivo.

Resultados: Se seleccionaron un total de 96 referencias y se sintetizó la información de cada medicamento.

Los fármacos contraindicados en el embarazo son los retinoides tópicos, pimecrolimus, inhibidores de la ciclooxigenasa 2, metotrexato, micofenolato de mofetilo, leflunomida, acitretina, tiopurinas, apremilast, tofacitinib, baricitinib, anakinra, abatacept, tocilizumab, sarilumab, ixekizumab, risankizumab y tildrakizumab. Existe contraindicación en la lactancia para los mismos excepto para las tiopurinas y tocilizumab y están contraindicados rituximab, ustekinumab y secukinumab, no así en el embarazo donde se recomienda evitarlos. La mayoría son compatibles con la fertilidad masculina excepto algunos como los aminosalicilatos, micofenolato y leflunomida que tienen un tiempo concreto de suspensión de tratamiento previo, y la ciclosporina requiere una dosis inferior a 2mg/kg/día.

Conclusiones: En este contexto de tratamientos crónicos con potencial teratogénico, es necesario visibilizar la importancia de la planificación gestacional para seleccionar el fármaco más seguro.

Ante la calidad de los datos disponibles, sigue siendo necesaria la continua actualización de la información, así como el promover estudios observacionales de cohortes de pacientes embarazadas y hombres en edad fértil, incluso realizar estudios prospectivos, con el fin de generar mayor evidencia científica.

Palabras clave

enfermedades inflamatorias inmunomediadas, embarazo, lactancia, fertilidad, exposición paterna, inmunosupresores, biológicos

Referencias

Puig L, Ruiz de Morales JG, Dauden E, Luis Andreu J, Cervera R, Adán A, et al. Prevalence of ten Immune-mediated inflammatory diseases (IMID) in Spain. Rev Esp Salud Publica. 2019;93:e201903013.

Alijotas-Reig J, Esteve-Valverde E. Pregnancy and autoimmune diseases. Med Clin (Barc). 2017;148(4):161-3. DOI: 10.1016/j.medcli.2016.11.008.

Schwarb FP, Gabard B, Rufli T. Percutaneous absorption of salicylic acid in man after topical administration of three different formulations. Dermatology. 1999;198(1):44-51. DOI: 10.1159/000018063.

Rademaker M, Agnew K, Andrews M, Armour K, Baker C, Foley P, et al. Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration. Australas J Dermatol. 2018;59(2):86-100. DOI: 10.1111/ajd.12641.

Hoffman MB, Farhangian M, Feldman SR. Psoriasis during pregnancy: characteristics and important management recommendations. Expert Rev Clin Immunol. 2015;11(6):709-20. DOI: 10.1586/1744666X.2015.1037742.

Bae YS, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Young M, et al. Review of treatment options for psoriasis in pregnant or lactating women: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(3):459-77. DOI: 10.1016/j.jaad.2011.07.039.

Koh YP, Tian EA, Oon HH. New changes in pregnancy and lactation labelling: Review of dermatologic drugs. Int J Womens Dermatol. 2019;5(4):216-26. DOI: 10.1016/j.ijwd.2019.05.002.

Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation Part II. Lactation. J Am Acad Dermatol. 2014;70(3):417.e1-10. DOI: 10.1016/j.jaad.2013.09.009.

Bangsgaard N, Rørbye C, Skov L. Treating psoriasis during pregnancy: safety and efficacy of treatments. Am J Clin Dermatol. 2015;16(5):389-98. DOI: 10.1007/s40257-015-0137-5.

Pariser D. Topical corticosteroids and topical calcineurin inhibitors in the treatment of atopic dermatitis: focus on percutaneous absorption. Am J Ther. 2009; 16(3):264-73. DOI: 10.1097/MJT.0b013e31818a975c.

Toda K. Is acetaminophen safe in pregnancy? Scand J Pain. 2017;17:445-6. DOI: 10.1016/j.sjpain.2017.09.007.

Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part II: analgesics and other drugs used in rheumatology practice. Rheumatology (Oxford). 2016;55(9):1698-702. DOI: 10.1093/rheumatology/kev405.

Smeele HTW, Dolhain RJEM. Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Semin Arthritis Rheum. 2019;49(3S):S32-5. DOI: 10.1016/j.semarthrit.2019.09.010.

Sapag Durán AM, Nasswette G. Riesgo de drogas antirreumáticas frecuentemente usadas durante el embarazo. Rev Arg Reumatol. 2012;23(4):62-70.

Micu MC, Ostensen M, Villiger PM, Micu R, Ionescu R. Paternal exposure to antirheumatic drugs-What physicians should know: Review of the literature. Semin Arthritis Rheum. 2018;48(2):343-55. DOI: 10.1016/j.semarthrit.2018.01.006.

Dathe K, Padberg S, Hultzsch S, Koehler L-M, Meixner K, Fietz A-K, et al. Exposure to cox-2 inhibitors (coxibs) during the first trimester and pregnancy outcome: a prospective observational cohort study. Eur J Clin Pharmacol. 2018;74(4):489-95. DOI: 10.1007/s00228-017-2385-1.

Bérard A, Sheehy O, Girard S, Zhao JP, Bernatsky S. Risk of preterm birth following late pregnancy exposure to NSAIDs or COX-2 inhibitors. Pain. 2018;159(5):948-55. DOI: 10.1097/j.pain.0000000000001163.

Gardiner SJ, Doogue MP, Zhang M, Begg EJ. Quantification of infant exposure to celecoxib through breast milk. Br J Clin Pharmacol. 2006;61(1):101-4. DOI: 10.1111/j.1365-2125.2005.02520.x.

Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: A meta-analysis. Reprod Toxicol. 2008;25(2):271-5. DOI: 10.1016/j.reprotox.2007.11.010.

Branski D, Kerem E, Gross-Kieselstein E, Hurvitz H, Litt R, Abrahamov A. Bloody diarrhea: a possible complication of sulfasalazine transferred through human breast milk. J Pediatr Gastroenterol Nutr. 1986;5(2):316-7.

Mouyis M, Flint JD, Giles IP. Safety of anti-rheumatic drugs in men trying to conceive: a systematic review and analysis of published evidence. Semin Arthritis Rheum. 2019;48(5):911-20. DOI: 10.1016/j.semarthrit.2018.07.011.

Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016;55(9):1693-7. DOI: 10.1093/rheumatology/kev404.

Polifka JE, Friedman JM. Teratogen update: azathioprine and 6-mercaptopurine. Teratology 2002;65(5):240-61. DOI: 10.1002/tera.10043.

Mahadevan U, Martin CF, Sandler RS, Kane SV, Dubinsky M, Lewis JD, et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy [abstract]. Gastroenterology. 2012;142: S-149.

Mahadevan U, McConnell RA, Chambers CD. Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease. Gastroenterology. 2017;152(2):451-62. DOI: 10.1053/j.gastro.2016.10.013.

Hutson JR, Matlow JN, Moretti ME, Koren G. The fetal safety of thiopurines for the treatment of inflammatory bowel disease in pregnancy. J Obstet Gynaecol. 2013;33(1):1-8. DOI: 10.3109/01443615.2012.716106.

Puchner A, Groochenig HP, Sautner J, Helmy-Bader Y, Juch H, Reinisch S, et al. Immunosuppressives and biologics during pregnancy and lactation: A consensus report issued by the Austrian Societies of Gastroenterology and Hepatology and Rheumatology and Rehabilitation. Wien Klin Wochenschr. 2019;131(1-2):29-44. DOI: 10.1007/s00508-019-1448-y.

Biancone L, Annese V, Ardizzone S, Armuzzi A, Calabrese E, Caprioli F, et al. Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis. 2017;49(4):338-58. DOI: 10.1016/j.dld.2017.01.141.

McConnell RA, Mahadevan U. Pregnancy and the Patient with Inflammatory Bowel Disease Fertility, Treatment, Delivery, and Complications. Gastroenterol Clin North Am. 2016;45(2):285-301. DOI: 10.1016/j.gtc.2016.02.006.

Cury DB, Moss AC. Treatment of Crohn's disease in pregnant women: Drug and multidisciplinary approaches. World J Gastroenterol. 2014;20(27):8790-5. DOI: 10.3748/wjg.v20.i27.8790.

Christensen LA, Dahlerup JF, Nielsen MJ, Fallingborg JF, Schmiegelow K. Azathioprine treatment during lactation. Aliment Pharmacol Ther. 2008;28(10):1209-13. DOI: 10.1111/j.1365-2036.2008.03843.x.

Norgard B, Pedersen L, Jacobsen J, Rasmussen SN, Sorensen HT. The risk of congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine before conception. Aliment Pharmacol Ther. 2004;19(6):679-85. DOI: 10.1111/j.1365-2036.2004.01889.x.

Akbari M, Shah S, Velayos FS, Mahadevan U, Cheifetz AS. Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(1):15-22. DOI: 10.1002/ibd.22948.

Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, et al. Birth defects after maternal exposure to corticosteroids: Prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385-92. DOI: 10.1002/1096-9926(200012)62:6<385::AID-TERA5>3.0.CO;2-Z.

Kavanaugh. Proceedings From the American College of Rheumatology Reproductive Health Summit: The Management of Fertility, Pregnancy, and Lactation in Women With Autoimmune and Systemic Inflammatory Diseases. Arthritis Care Res (Hoboken). 2015;67(3):313-25. DOI: 10.1002/acr.22516.

Zakhem GA, Motosko CC, Mu EW, Ho RS. Infertility and teratogenicity after paternal exposure to systemic dermatologic medications: A systematic review. J Am Acad Dermatol. 2019;80(4):957-69. DOI: 10.1016/j.jaad.2018.09.031.

Nurmohamed L, Moretti ME, Schechter T, Einarson A, Johnson D, Lavigne SV, et al. Outcome following high-dose methotrexate in pregnancies misdiagnosed as ectopic. Am J Obst Gynecol. 2011;205(6):533.e1-3. DOI: 10.1016/j.ajog.2011.07.002.

Weber-Schoendorfer C, Hoeltzenbein M, Wacker E, Meister R, Schaefer C. No evidence for an increased risk of adverse pregnancy outcome after paternal low-dose methotrexate: an observational cohort study. Rheumatology (Oxford). 2014;53(4):757-63. DOI: 10.1093/rheumatology/ket390.

Weber-Schoendorfer C, Chambers C, Wacker E, Beghin D, Bernard N; Network of French Pharmacovigilance Centers. Pregnancy outcome after methotrexate treatment for rheumatic disease prior to or during early pregnancy: a prospective multicenter cohort study. Arthritis Rheumatol. 2014;66(5):1101–10. DOI: 0.1002/art.38368.

Petri M. Immunosuppressive Drug Use in Pregnancy. Autoimmunity. 36(1):51-6. DOI: 10.1080/0891693031000067296.

Leroy C, Rigot JM, Leroy M, Decanter C, Le Mapihan K, Parent AS, et al. Immunosuppressive drugs and fertility. Orphanet J Rare Dis. 2015;10:136. DOI: 10.1186/s13023-015-0332-8.

Haberman J, Karwa G, Greenstein SM, Soberman R, Glicklich D, Tellis V,, et al. Male fertility in cyclosporine-treated renal transplant patients. J Urol. 1991;145(2):294‐6. DOI:10.1016/s0022-5347(17)38318-0.

Georgiou GK, Dounousi E, Harissis HV. Calcineurin inhibitors and male fertility after renal transplantation - a review. Andrologia. 2016; 48(5):483-90. DOI:10.1111/and.12477.

Xu LG, Yang YR, Wang HW, Qiu F, Peng WL, Xu HM, et al. Characteristics of male fertility after renal transplantation. Andrologia. 2011;43(3):203‐7. DOI:10.1111/j.1439-0272.2010.01052.

Coscia LA, Armenti DP, King RW, Sifontis NM, Constantinescu S, Moritz MJ. Up date on the teratogenicity of maternal mycophenolate mofetil. J Pediatr Genet. 2015;4(2):42-55. DOI: 10.1055/s-0035 1556743.

Hoeltzenbein M, Elefant E, Vial T, Finkel-Pekarsky V, Stephens S, Clementi M, et al. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am J Med Genet A. 2012;158A(3):588-96. DOI: 10. 1002/ajmg.a.35223.

Skorpen CG, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75(5):795-810. DOI: 10.1136/annrheumdis-2015-208840.

Midtvedt K, BerganS, Reisæter AV, Vikse BE, Åsberg A. Exposure to mycophenolate and fatherhood. Transplantation. 2017;101(7): e214-7. DOI: 10.1097/TP.0000000000001747.

Motta M, Tincani A, Faden D, Zinzini E, Lojacono A, Marchesi A, et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25(2):86-9. DOI: 10.1038/sj.jp.7211208.

Levy RA, Vilela VS, Cataldo MJ, Ramos RC, Duarte JL, Tura BR, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus. 2001(6);10:401-4. DOI: 10.1191/096120301678646137.

Osadchy A, Ratnapalan T, Koren G. Ocular Toxicity in Children Exposed in Utero to Antimalarial Drugs: Review of the Literature. J Rheuma. 2011;38(12):2504-8. DOI: 10.3899/jrheum.110686.

Cassina M, Johnson DL, Robinson LK, Braddock SR, Xu R, Jimenez JL, et al. Pregnancy outcome in women exposed to leflunomide before or during pregnancy. Arthritis Rheum. 2012;64(7):2085-94. DOI: 10.1002/art.34419.

Warnke C, Stüve O, Kieseier BC. Teriflunomide for the treatment of multiple sclerosis. Clin Neurol Neurosurg. 2013;115 Suppl 1:S90-4. DOI: 10.1016/j.clineuro.2013.09.030.

Chambers CD, Johnson DL, Robinson LK, Braddock SR, Xu R, Lopez-Jimenez J, et al. Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum. 2010;62(5):1494-503. DOI: 10.1002/art.27358.

Brent RL. Teratogen update: reproductive risks of Leflunomide (Arava); a pyrimidines synthesis inhibitor: counseling women taking leflunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a child. Teratology. 2001;63(2):106-12. DOI: 10.1002/1096-9926(200102)63:2<106::AID-TERA1017>3.0.CO;2-R.

Picardo S, Seow CH. A Pharmacological Approach to Managing Inflammatory Bowel Disease During Conception, Pregnancy and Breastfeeding: Biologic and Oral Small Molecule Therapy. Drugs. 2019;79(10):1053-63. DOI: 10.1007/s40265-019-01141-w.

Millsop JW, Heller MM, Eliason MJ, Murase JE. Dermatological medication effects on male fertility. Dermatol Ther. 2013;26(4):337-46. DOI: 10.1111/dth.12069.

Clowse ME, Feldman SR, Isaacs JD, Kimball AB, Strand V, Warren RB, et al. Pregnancy outcomes in the tofacitinib safety database for rheumatoid arthritis and psoriasis. Drug Saf. 2016;39(8):755-62. DOI: 10.1007/s40264-016-0431-z.

Gerosa M, Argolini LM, Artusi C, Chighizola CB. The use of biologics and small molecules in pregnant patients with rheumatic diseases. Expert Rev Clin Pharmacol. 2018;11(10):987-98. DOI: 10.1080/17512433.2018.1525293.

Grunewald S, Jank A. New systemic agents in dermatology with respect to fertility, pregnancy, and lactation. J Dtsch Dermatol Ges. 2015;13(4):277-89. DOI: 10.1111/ddg.12596.

Chambers CD, Johnson DL, Xu R, Luo Y, Lopez-Jimenez J, Adam MP, et al; OTIS Collaborative Research Group. Birth outcomes in women who have taken adalimumab in pregnancy: A prospective cohort study. PLoS One. 2019;14(10):e0223603. DOI: 10.1371/journal.pone.0223603.

Burmester GR, Landewé R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, et al. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76(2):414-7. DOI: 10.1136/annrheumdis-2016-209322.

Pottinger E, Woolf RT, Exton LS, Burden AD, Nelson-Piercy C, Smith CH. Exposure to biological therapies during conception and pregnancy: a systematic review. Br J Dermatol. 2018;178(1):95‐102. DOI: 10.1111/bjd.15802.

Heppt F, Colsman A, Maronna A, Uslu U, Heppt MV, Kiesewetter F, et al. Influence of TNF-alpha inhibitors and fumaric acid esters on male fertility in psoriasis patients. J Eur Acad Dermatol Venereol. 2017;31(11):1860-6. DOI: 10.1111/jdv.14364.

Carter JD, Valeriano J, Vasey FB. Tumor necrosis factor-alpha inhibition and VATER association: A causal relationship. J Rheumatol. 2006;33(5):1014-7.

Mahadevan U, Cucchiara S, Hyams JS et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organisation: pregnancy and pediatrics. Am J Gastroenterol. 2011;106(2):214-23. DOI: 10.1038/ajg.2010.464.

Clark DA. Anti-TNF alpha therapy in immune-mediated subfertility: State of the art. J Reprod Immunol. 2010;85(1):15-24. DOI: 10.1016/j.jri.2010.01.007.

Nielsen OH, Loftus EV Jr, Jess T. Safety of TNF-alpha inhibitors during IBD pregnancy: a systematic review. BMC Med. 2013;11:174. DOI: 10.1186/1741-7015-11-174.

Ostensen M. Safety issues of biologics in pregnant patients with rheumatic diseases. Ann N Y Acad Sci. 2014;1317:32-8. DOI: 10.1111/nyas.12456.

Matro R, Martin CF, Wolf DC. Detection of biologic agents in breast milk and implication for infection, growth and development in infants born to women with inflammatory bowel disease: results from the PIANO registry [abstract]. Gastroenterology. 2015;148:S-141.

Paschou S, Voulgari PV, Vrabie IG, Saougou IG, Drosos AA. Fertility and reproduction in male patients with ankylosing spondylitis treated with infliximab. J Rheumatol. 2009;36(2):351-4. DOI: 0.3899/jrheum.080554.

Perdichizzi A, Nicoletti F, La Vignera S, Barone N, D’Agata R, Vicari E, et al. Effects of tumour necrosis factor-alpha on human sperm motility and apoptosis. J Clin Immunol. 2007;27(2):152-62. DOI: 10.1007/s10875-007-9071-5.

Villiger PM, Caliezi G, Cottin V, Förger F, Senn A, Østensen M. Effects of TNF antagonists on sperm characteristics in patients with spondyloarthritis. Ann Rheum Dis. 2010;69(10):1842-4. DOI: 10.1136/ard.2009.127423.

Clowse MEB, Scheuerle AE, Chambers C, Afzali A, Kimball AB, Cush JJ, et al. Pregnancy outcomes after exposure to certolizumab pegol: Updated results from a pharmacovigilance safety database. Arthritis Rheumatol. 2018;70(9):1399-407. DOI: 10.1002/art.40508.

Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14(8):1673-6. DOI: 10.1111/jth.13366.

Giles I, Yee CS, Gordon C. Stratifying management of rheumatic disease for pregnancy and breastfeeding. Nat Rev Rheumatol. 2019;15(7):391-402. DOI: 10.1038/s41584-019-0240-8.

Ostensen M. The use of biologics in pregnant patients with rheumatic disease. Expert Rev Clin Pharmacol. 2017;10(6):661-9. DOI: 10.1080/17512433.2017.1305268.

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). Clin Exp Rheumatol. 2011; 29(6):1021-3.

Chang Z, Spong CY, Jesus AA, Davis MA, Plass N, Stone DL, et al. Anakinra use during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS). Arthritis Rheumatol. 2014;66(11):3227-32. DOI: 10.1002/art.38811.

Youngstein T, Hoffmann P, Gül A, Lane T, Williams R, Rowczenio DM, et al. International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors. Rheumatology (Oxford). 2017;56(12):2102-8. DOI: 10.1093/rheumatology/kex305.

Pham T, Bachelez H, Berthelot JM, Blacher J, Claudepierre P, Constantin A, et al. Abatacept therapy and safety management. Joint Bone Spine. 2012;79 Suppl 1:3-84. DOI: 0.1016/S1297-319X(12)70011-8.

Kumar M, Ray L, Vemuri S, Simon TA. Pregnancy outcomes following exposure to abatacept during pregnancy. Semin Arthritis Rheum. 2015;45(3):351-6. DOI: 10.1016/j.semarthrit.2015.06.016.

Hoeltzenbein M, Becka E, Rajwanshi R, Skorpen CG, Berber E, Schaefer C, et al. Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data. Semin Arthritis Rheum. 2016;46(2):238-45. DOI: 10.1016/j.semarthrit.2016.05.004.

Sakurai T, Takai R, Burgin H, Ishihara K, Sakamoto Y, Amano J, et al. The effects of interleukin-6 signal blockade on fertility, embryo-fetal development, and immunization in vivo. Birth Defects Res B Dev Reprod Toxicol. 2012;95(4):304-17. DOI: 10.1002/bdrb.21019.

Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011;117(5):1499-506. DOI: 10.1182/blood-2010-07-295444.

Klink DT, van Elburg RM, Schreurs MW, van Well GT. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol. 2008;2008:271363. DOI: 10.1155/2008/271363.

Owczarek W, Walecka I, Lesiak A, Czajkowski R, Reich A, Zerda I, et al. The use of biological drugs in psoriasis patients prior to pregnancy, during pregnancy and lactation: a review of current clinical guidelines. Postepy Dermatol Alergol. 2020;37(6):821-30. DOI: 10.5114/ada.2020.102089.

Schaufelberg BW, Horn E, Cather JC, Rahawi KW. Pregnancy outcomes in women exposed to ustekinumab in the psoriasis clinical development program [abstract]. J Am Acad Dermatol. 2014;70:AB178.

Mahadevan U, Vermeire S, Lasch K, Abhyankar B, Bhayat F, Blake A, et al. Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;45(7):941-50. DOI: 10.1111/apt.13960.

Wieringa JW, Driessen GJ, Van der Woude CJ. Pregnant women with inflammatory bowel disease: the effects of biologicals on pregnancy, outcome of infants, and the developing immune system. Expert Rev Gastroenterol Hepatol. 2018;12(8):811-8. DOI: 10.1080/17474124.2018.1496820.

Moens A, van der Woude CJ, Julsgaard M, Humblet E, Sheridan J, Baumgart DC, et al. Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study. Aliment Pharmacol Ther. 2020;51(1):129-38. DOI: 10.1111/apt.15539.

Julsgaard M, Kjeldsen J, Bibby BM, Brock B, Baumgart DC. Vedolizumab concentrations in the breast milk of nursing mothers with inflammatory bowel disease. Gastroenterology. 2018;154(3):752-4.e1. DOI: 10.1053/j.gastro.2017.08.067.

Warren RB, Reich K, Langley RG, Strober B, Gladman D, Deodhar A, et al. Secukinumab in pregnancy: outcomes in psoriasis, psoriatic arthritis and ankylosing spondylitis from the global safety database. Br J Dermatol. 2018;179(5):1205-7. DOI: 10.1111/bjd.16901.

Irani V, Guy AJ, Andrew D, Beeson JG, Ramsland PA, Richards JS. Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases. Mol Immunol. 2015;67(2 Pt A):171-82. DOI: 10.1016/j.molimm.2015.03.255.

Haycraft K, DiRuggiero D, Rozzo SJ, Mendelsohn AM, Bhutani T. Outcomes of Pregnancies from the tildrakizumab phase I-III clinical development program. Br J Dermatol. 2020;183(1):184-6. DOI: 10.1111/bjd.18897.

Odufalu FD, Long M, Lin K, Mahadevan U; PIANO Investigators from the Crohn’s and Colitis Foundation (CCF) Clinical Research Alliance recruited patients for their respective centers for participant enrollment. Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry. Gut. 2021:gutjnl-2021-325317. DOI: 10.1136/gutjnl-2021-325317.

Leung KK, Tandon P, Govardhanam V, Maxwell C, Huang V. The Risk of Adverse Neonatal Outcomes With Maternal Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Inflamm Bowel Dis. 2021:27(4):550-62. DOI: 10.1093/ibd/izaa122.

Kimball AB, Guenther L, Kalia S, de Jong EMGJ, Lafferty KP, Chen DY, Langholff W, Shear NH. Pregnancy Outcomes in Women With Moderate-to-Severe Psoriasis From the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2021 Mar 1;157(3):301-306. doi: 10.1001/jamadermatol.2020.5595. PMID: 33533924; PMCID: PMC7859871.

Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD,et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Apr;72(4):529-556. doi: 10.1002/art.41191. Epub 2020 Feb 23. PMID: 32090480.