Preparo dos pacientes com doença inflamatória intestinal para terapia biológica na prática clínica
DOI:
https://doi.org/10.34019/1982-8047.2019.v45.28789Palabras clave:
Doenças Inflamatórias Intestinais, Imunossupressores, Terapia Biológica, Rastreio, ImunizaçãoResumen
Introdução: A terapia biológica revolucionou o tratamento das doenças inflamatórias intestinais (DII). Embora muito efetivas, as medicações biológicas colocam os pacientes em maior risco de desenvolvimento de reações infusionais e paradoxais, infecções e alguns tipos de câncer como linfomas, este último especialmente quando feita em combinação com tiopurinas. A adequada seleção, aconselhamento e educação dos pacientes são itens importantes para o uso bem sucedido dos biológicos. Objetivo: Revisar a melhor estratégia para mostrar uma visão atualizada das etapas imprescindíveis no preparo dos pacientes com DII para terapia biológica. Material e Métodos: Realizou-se uma revisão sistemática da literatura, em fevereiro de 2018, utilizando os termos de pesquisa: “doença de Crohn”, “doença inflamatória intestinal”, “imunização”, “imunossupressores” e “terapia biológica”, em língua inglesa e portuguesa. Foram incluídos apenas artigos originais e de revisão. Discussão e Conclusão: Uma história detalhada para excluir contraindicações destas medicações e um monitoramento baseado em diretrizes são passos importantes antes de iniciar a terapia. Biológicos devem ser considerados somente se uma avaliação confirmar que o paciente tem doença ativa. É relevante também excluir condições que mimetizam a atividade de doença. Até o momento, os agentes biológicos demonstraram um perfil de segurança favorável em pacientes com DII. No entanto, é importante que o início da terapia biológica seja discutido atentamente com os pacientes, explicando os riscos e benefícios do tratamento. Antes de iniciar o uso de biológicos, os pacientes necessitam ser rastreados para tuberculose latente, hepatites B e C, e infecção por HIV. Idealmente, o status vacinal deve ser verificado e atualizado antes do início da terapia imunossupressora. As diretrizes atuais recomendam aos pacientes adultos com DII o mesmo esquema de imunização de rotina da população geral, evitando as vacinas de agentes vivos durante a terapia imunossupressora. Todas essas medidas são essenciais para estabelecer de forma segura a terapia esperada pelo uso de biológicos.
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Park SH, Aniwan S, Loftus EV Jr. Advances in the use of biologics and other novel drugs for managing inflammatory bowel disease. Curr Opin Pharmacol. 2017; 37:65-71. doi: 10.1016/j.coph.2017.09.007
Souza GS, Vidigal FM, Chebli LA, Ribeiro TCR, Furtado MC, Pace FHL et al. Effect of azathioprine or mesalazine therapy on incidence of re-hospitalization in sub-occlusive ileocecal Crohn’s disease patients. Med Sci Monit. 2013; 19:716-22. doi: 10.12659/MSM.889196
Peyrin-Biroulet L, Panés J, Sandborn WJ, Vermeire S, Danese S, Feagan BG et al. Defining disease severity in inflammatory bowel diseases: current and future directions. Clin Gastroenterol Hepatol. 2016; 14(e17):348-54. doi: 10.1016/j.cgh.2015.06.001
Santos JCD, Malaguti C, Lucca FA, Cabalzar AL, Ribeiro TCR, Gaburri PD et al. Impact of biological therapy on body composition of patients with Chron’s disease. Rev Assoc Med Bras. 2017; 63:407-13. doi: 10.1590/1806-9282.63.05.407
Peyrin-Biroulet L, Fiorino G, Buisson A, Danese S. Firstline therapy in adult Crohn’s disease: who should receive antiTNF agents? Nat Rev Gastroenterol Hepatol. 2013; 10:345-51. doi: 10.1038/nrgastro.2013.31
Pouillon L, Bossuyt P, Peyrin-Biroulet L. Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease. Expert Opin Biol Ther. 2016; 16:1277-90. doi: 10.1080/14712598.2016.1203897
Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis. 2017; 11:3-25. doi: 10.1093/ecco-jcc/jjw168
Chebli JM, Gaburri PD, Chebli LA, Ribeiro TCR, Pinto AL, Ambrogini Júnior O, Damião AO. A guide to prepare patients with inflammatory bowel diseases for anti-TNF-α therapy. Med Sci Monit. 2014; 20:487-98. doi: 10.12659/MSM.890331
Lahiff C, Safaie P, Awais A, Akbari M, Gashin L, Sheth S et al. The Crohn’s disease activity index (CDAI) is similarly elevated in patients with Crohn’s disease and in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2013; 37:786-94. doi: 10.1111/apt.12262
Kane SV. Preparing for biologic or immunosuppressant therapy. Gastroenterol Hepatol 2011; 7:544-46.
Schoepfer AM, Beglinger C, Straumann A, Safroneeva E, Romero Y, Armstrong D et al. Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index,Creactive protein, platelets, hemoglobin, and blood leukocytes. Inflamm Bowel Dis. 2013; 19:332-41. doi: 10.1097/MIB.0b013e3182810066
Schoepfer AM, Beglinger C, Straumann A, Trummler M, Vavricka SR, Bruegger LE et al. Fecal calprotectin correlates more closely with the simple endoscopic score for Crohn’s disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol. 2010; 105:162-69. doi: 10.1038/ajg.2009.545
Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N et al. C-Reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Am J Gastroenterol. 2015; 110:802-19. doi: 10.1038/ajg.2015.120
Quigley EM. Overlapping irritable bowel syndrome and inflammatory bowel disease: less to this than meets the eye? Therap Adv Gastroenterol. 2016; 9(2):199-212. doi: 10.1177/1756283X15621230
Halpin SJ, Ford AC. Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2012; 107:1474-82. doi: 10.1038/ajg.2012.260
Camilleri M. Managing symptoms of irritable bowel syndrome in patients with inflammatory bowel disease. Gut. 2011; 60: 425-8. doi: 10.1136/gut.2010.234583
Meng J, Agrawal A, Whorwell PJ. Refractory inflammatory bowel disease-could it be an irritable bowel? Nat Rev Gastroenterol Hepatol. 2013; 10:58-61. doi: 10.1038/nrgastro.2012.173
Chebli JM, Abreu NC, Chebli LA, Reboredo MM, Pinheiro HS. Intestinal spirochetosis: an unusual cause of IBD flare-up during anti-TNF therapy. Int J Colorectal Dis. 2016; 31:745-46. doi: 10.1007/s00384-015-2240-8
Rao K, Higgins PD. Epidemiology, diagnosis, and management of clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016; 22:1744-54. doi: 10.1097/MIB.0000000000000793
Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis: Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis. 2017; 11:649-70. doi: 10.1093/ ecco-jcc/jjx008
Sager K, Alam S, Bond A, Chinnappan L, Probert CS. Review article: cytomegalovirus and inflammatory bowel disease. Aliment Pharmacol Ther. 2015; 41:725-33. doi: 10.1111/ apt.13124
Ricci Júnior JE, Chebli LA, Ribeiro TCR, Castro AC, Gaburri PD, Pace FHL et al. Small intestinal bacterial overgrowth is associated with concurrent intestinal inflammation but not with systemic inflammation in Crohn’s disease patients. J Clin Gastroenterol. 2018; 52(6):530-36. doi: 10.1097/MCG.0000000000000803
Di Sario A, Bendia E, Schiadà L, Sassaroli P, Benedetti A. Biologic drugs in Crohn’s disease and ulcerative colitis: safety profile. Curr Drug Saf. 2016; 11:55-61. doi: 10.2174/157488631101160212171757
Cohn HM, Dave M, Loftus EV Jr. Understanding the cautions and contraindications of immunomodulator and biologic therapies for use in inflammatory bowel disease. Inflamm Bowel Dis. 2017; 23:1301-15. doi: 10.1097/MIB.0000000000001199
Siegel CA. Shared decision making in inflammatory bowel disease: helping patients understand the tradeoffs between treatment options. Gut. 2012; 61:459-65. doi: 10.1136/ gutjnl-2011-300988
Annese V, Beaugerie L, Egan L, Biancone L, Bolling C, Brandts C et al. European evidence-based consensus: inflammatory bowel disease and malignancies. J Crohns Colitis. 2015; 9:945-65. doi: 10.1093/ecco-jcc/jjv141
Cosnes J. What should be done in inflammatory bowel disease patients with prior malignancy? Dig Dis. 2017; 35:50-5. doi: 10.1159/000449083
Siegel CA. Review article: explaining risks of inflammatory bowel disease therapy to patients. Aliment Pharmacol Ther. 2011; 33:23-32. doi: 10.1111/j.1365-2036.2010.04489.x
Ardura SST, Monica I, Siegel JD, Lu Ying, Bousvaros A, Crandall W. NASPGHAN clinical report: surveillance, diagnosis, and prevention of infectious diseases in pediatric patients with inflammatory bowel disease receiving tumor necrosis factor-alfa inhibitors. J Pediatr Gastroenterol Nutr. 2016; 63:130-55. doi: 10.1097/MPG.0000000000001188
Cosnes J. Smoking and diet: impact on disease course? Dig Dis. 2016; 34(1-2):72-7. doi: 10.1159/000442930
Abreu C, Sarmento A, Magro F. Screening, prophylaxis and counselling before the start of biological therapies: a practical approach focused on IBD patients. Dig Liver Dis. 2017; 49(12):1289-97. doi: 10.1016/j.dld.2017.09.002
Park SH, Aniwan S, Loftus EV Jr. Advances in the use of biologics and other novel drugs for managing inflammatory bowel disease. Curr Opin Pharmacol. 2017; 37:65-71. doi: 10.1016/j.coph.2017.09.007
Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis. 2017; 11:3-25. doi: 10.1093/ecco-jcc/jjw168
Bartalesi F, Scirè C, Requena-Méndez A, Abad MA, Buonfrate D, Caporali R et al. Recommendations for infectious disease screening in migrants to Western Europe with inflammatory arthropathies before starting biologic agents: results from a multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI) facing the largest impact of the flow of migrants today. Clin Exp Rheumatol. 2017; 35:752-65.
Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC et al. Asian Organization for Crohn’s and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment: part 1: risk assessment. J Gastroenterol Hepatol. 2018; 33(1):20-9. doi: 10.1111/jgh.14019
Dobler CC. Biologic Agents and Tuberculosis. Microbiol Spectrum. 2016; 4(6):1-10. doi: 10.1128/microbiolspec.
Abreu C, Afonso J, Camila Dias C, Ruas R, Sarmento A, Magro F. Serial tuberculosis screening in inflammatory bowel disease patients receiving anti-TNFα therapy. J Crohns Colitis. 2017; 11(10):1223-9. doi: 10.1093/ecco-jcc/jjx080
Wallis RS. Infectious complications of tumor necrosis factor blockade. Curr Opin Infect Dis. 2009; 22:403-9. doi: 10.1097/QCO.0b013e32832dda55
Abreu C, Almeida F, Ferraz R, Dias CC, Sarmento A, Magro F. The tuberculin skin test still matters for the screening of latent Tuberculosis infections among inflammatory bowel diseases patients. Dig Liver Dis. 2016; 48:1438-43. doi: 10.1016/j.dld.2016.08.107
Carmona L, Gómez-Reino JJ, Rodríguez-Valverde V, Montero D, Pascual-Gómez E, Mola EM et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005; 52:1766-72. doi: 10.1002/art.21043
Diel R, Loddenkemper R, Nienhaus A. Evidence-based comparison of commercial interferon-gamma release assays fordetecting active TB: a metaanalysis. Chest. 2010; 137:952-68. doi: 10.1378/chest.09-2350
Cotter J, Rosa B. The importance of IGRA in patients candidates for biological therapy. J Crohns Colitis. 2013; 7:928-9. doi: 10.1016/j.crohns.2013.02.013
Duarte R, Campainha S, Cotter J, Rosa B, Varela P, Correia A et al. Position paper on tuberculosis screening in patients with immune mediated inflammatory diseases candidates for biological therapy. Acta Reumatol Port. 2012; 37:253-9.
Theis VS, Rhodes JM. Review article: minimizing tuberculosis during anti-tumour necrosis factor-alpha treatment of inflammatory bowel disease. Aliment Pharmacol Ther. 2008; 27:19-30. doi: 10.1111/j.1365-2036.2007.03553.x
Geiter LJ, Gordin FM, Hershfield E, Horsburgh CR, Jereb JA, Jordan TJ et al. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000; 161(3):S221-47. doi: 10.1164/ ajrccm.161.supplement_3.ats600
Degasperi E, Caprioli F, El Sherif O, Back D, Colombo M, Aghemo A. Challenges in treating patients with inflammatory bowel disease and concurrent viral hepatitis infection. Expert Rev Gastroenterol Hepatol. 2016; 10:1373-83. doi: 10.1080/17474124.2016.1246181
Dusheiko G. Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues. Liver Int. 2013; 33:137-50. doi: 10.1111/liv.12078
Loras C, Saro C, Gonzalez-Huix F, Mínguez M, Merino O, Gisbert JP et al. Prevalence and factors related to hepatitis B and C in inflammatory bowel disease patients in Spain: a nationwide, multicenter study. Am J Gastroenterol. 2009; 104:57-63. doi: 10.1038/ajg.2008.4
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007; 45:507-39. doi: 10.1002/hep.21513
Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014; 8(6):443-68. doi: 10.1016/j.crohns.2013.12.013
Loras C, Gisbert JP, Mínguez M, Merino O, Bujanda L, Saro C et al. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. Gut. 2010; 59(10):1340-6. doi: 10.1136/gut.2010.208413
Loras C, Gisbert JP, Saro MC, Piqueras M, Sánchez-Montes C, Barrio J et al. Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: multicenter prospective observational study (REPENTINA 3). J Crohns Colitis. 2014; 8(11):1529-38. doi: 10.1016/j.crohns.2014.06.009
Belle A, Baumann C, Bigard MA, Zallot C, Gizard E, Guéant JL et al. Impact of immunosuppressive therapy on hepatitis B vaccination in inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2015; 27(8):877-81. doi: 10.1097/MEG.0000000000000370
Farraye FA. Vaccination of Patients with Inflammatory Bowel Disease. Gastroenterol Hepatol. 2017; 3:431-4.
Rojas-Feria M, Castro M, Suárez E, Ampuero J, Romero-Gómez M. Hepatobiliary manifestations in inflammatory bowel disease: the gut, the drugs and the liver. World J Gastroenterol. 2013; 19(42):7327-40. doi: 10.3748/wjg.v19.i42.7327
Seto WK, Wong DK, Chan TS, Hwang YY, Fung J, Liu KS et al. Association of hepatitis B core-related antigen with hepatitis B virus reactivation in occult viral carriers undergoing high-risk immunosuppressive therapy. Am J Gastroenterol. 2016; 111(12):1788-95. doi: 10.1038/ ajg.2016.436
European Association for the Study of the Liver. EASL 2017 Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017; 67(2):370-98. doi: 10.1016/j.jhep.2017.03.021
López-Serrano P, Pérez-Calle JL, Sánchez-Tembleque MD. Hepatitis B and inflammatory bowel disease: role of antiviral prophylaxis. World J Gastroenterol. 2013; 19:1342-8. doi: 10.3748/wjg.v19.i9.1342
Gisbert JP, Chaparro M, Esteve M. Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2011; 33:619-33.
Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008; 49(4):652-7. doi: 10.1016/j.jhep.2008.07.014
Shouval D, Shibolet O. Immunosuppression and HBV reactivation. Semin Liver Dis. 2013; 33:167-77. doi: 10.1055/ s-0033-1345722
Allen AM, Kim WR, Larson J, Loftus EV Jr. Efficacy and safety of treatment of hepatitis C in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013; 11:1655-60. doi: 10.1016/j.cgh.2013.07.014
Sansone S, Guarino M, Castiglione F, Rispo A, Auriemma F, Loperto I et al. Hepatitis B and C virus reactivation in immunosuppressed patients with inflammatory bowel disease. World J Gastroenterol. 2014; 20(13):3516-24. doi: 10.3748/wjg.v20.i13.3516
Campbell S, Ghosh S. Infliximab therapy for Crohn’s disease in the presence of chronic hepatitis C infection. Eur J Gastroenterol Hepatol. 2001; 13:191-2.
European Association for Study of Liver. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol. 2016; 66:153-94. doi: 10.1016/ j.jhep.2016.09.001
Peyrin-Biroulet L, Cadranel JF, Nousbaum JB, Oussalah A, Seddik M, Canva V et al. Interaction of ribavirin with azathioprine metabolism potentially induces myelosuppression. Aliment Pharmacol Ther. 2008; 28(8):984-93. doi: 10.1111/j.1365-2036.2008.03812.x
Pasquereau S, Kumar A, Herbein G. Targeting TNF and TNF receptor pathway in HIV-1 infection: from immune activation to viral reservoirs. Viruses. 2017; 9(4):pii: E64. doi: 10.3390/ v9040064
Ting PT, Koo JY. Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients. Int J Dermatol. 2006; 45:689-92.
Gaylis, N. Infliximab in the treatment of an HIV positive patient with Reiter’s syndrome. J Rheumatol. 2003; 30:407-11.
Gallitano SM, McDermott L, Brar K, Lowenstein E. Use of tumor necrosis factor (TNF) inhibitors in patients with HIV/AIDS. J Am Acad Dermatol. 2016; 74:974-80. doi: 10.1016/j.jaad.2015.11.043
Wangsiricharoen S, Ligon C, Gedmintas L, Dehrab A, Tungsiripat M, Bingham C et al. The rates of serious infections in HIV-infected patients who received tumor necrosis factor (TNF)-α inhibitor therapy for concomitant autoimmune diseases. Arthritis Care Res. 2016; 69:449-52. doi: 10.1002/acr.22955
Long MD, Gulati A, Wohl D, Herfarth H. Immunizations in pediatric and adult patients with inflammatory bowel disease: a practical case-based approach. Inflamm Bowel Dis. 2015; 21(8):1993-2003. doi: 10.1097/MIB.0000000000000395
Gisbert JP, Chaparro M. Vaccination strategies in patients with IBD. Nat Rev Gastroenterol Hepatol. 2013; 10:277-85. doi: 10.1038/nrgastro.2013.28
Kantsø B, Simonsen J, Hoffmann S, Valentiner-Branth P, Petersen AM, Jess T. Inflammatory bowel disease patients are at increased risk of invasive pneumococcal disease: a nationwide Danish cohort study 1977-2013. Am J Gastroenterol. 2015; 110:1582-7. doi: 10.1038/ajg.2015.284
Reich J, Wasan SK, and Farraye FA. Vaccination and health maintenance issues to consider in patients with inflammatory bowel disease. Gastroenterol Hepatol. 2017: 13(12):717-24.
Melmed GY. Vaccination strategies for patients with inflammatory bowel disease on immunomodulators and biologics. Inflamm Bowel Dis. 2009; 15:1410-6. doi: 10.1002/ ibd.20943
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M et al. IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 58(3):309-18. doi: 10.1093/cid/cit816
Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017; 112:241-58. doi: 10.1038/ajg.2016.537
Harpaz R, Ortega-Sanchez IR, Seward JF. Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC): prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008; 57(RR-5):1-30.
Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014; 63:822-5.
Dipasquale V, Romano C. Vaccination strategies in pediatric inflammatory bowel disease. Vaccine. 2017; 35(45):6070-5. doi: 10.1016/j.vaccine.2017.09.031
Gisbert JP, Chaparro M. Safety of anti-TNF agents during pregnancy and breastfeeding in women with inflammatory bowel disease. Am J Gastroenterol. 2013; 108:1426-38. doi: 10.1038/ajg.2013.171
Lu Y, Bousvaros A. Immunizations in children with inflammatory bowel disease treated with immunosuppressive therapy. Gastroenterol Hepatol. 2014; 10:355-63.
Veereman-Wauters G, Ridder L, Veres G, Kolacek S, Fell J, Malmborg P et al. Risk of infection and prevention in pediatric patients with IBD: ESPGHAN IBD Porto Group commentary. J Pediatr Gastroenterol Nutr. 2012; 54(6):830-7. doi: 10.1097/MPG.0b013e31824d1438
Mahadevan U, Wolf DC, Dubinsky M, Cortot A, Lee SD, Siegel CA et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013; 11(3):286-92. doi: 10.1016/j.cgh.2012.11.011
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
Gaidos JK, Kane SV. Managing IBD therapies in pregnancy. Curr Treat Options Gastroenterol. 2017; 15(1):71-83. doi: 10.1007/s11938-017-0123-5
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