|
1
|
Sousa P, Gisbert JP, Julsgaard M, Selinger CP, Chaparro M. Navigating Reproductive Care in Patients With Inflammatory Bowel Disease: A Comprehensive Review. J Crohns Colitis 2024; 18:ii16-ii30. [PMID: 39475080 PMCID: PMC11523042 DOI: 10.1093/ecco-jcc/jjae048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/26/2024] [Accepted: 04/27/2024] [Indexed: 11/02/2024]
Abstract
Inflammatory bowel disease [IBD] is often diagnosed in patients during their reproductive years. It is crucial that both healthcare providers and patients are adequately informed to avoid misguided decisions regarding family planning. One of the most important aspects during conception and pregnancy is to maintain disease remission, as disease activity is associated with adverse pregnancy outcomes. Apart from methotrexate, most conventional drugs used in IBD are considered low risk during conception and pregnancy. For newer agents, evidence is still limited. If needed, surgery must not be postponed and should ideally be performed in specialized centres. In most patients, delivery should be vaginal except for patients with complex perianal disease, with an ileoanal pouch anastomosis, or if there is an obstetric contraindication. In children exposed to biological treatments during pregnancy, the risk of infections appears to be low, and psychomotor development is probably not affected. Regarding immunizations, the standard vaccination schedule for inactivated vaccines should be followed for children exposed to biologics in utero. In the case of live vaccines, such as rotavirus, decisions should be individualized and take into consideration the risk-benefit ratio, particularly in developing countries. In this review, we provide a comprehensive and updated overview of aspects related to fertility, pregnancy, breastfeeding, and the impact on the care of children born to mothers with IBD. Both the available evidence and areas of uncertainty are discussed, with the goal of assisting healthcare professionals caring for IBD patients during this important stage of their lives.
Collapse
Affiliation(s)
- Paula Sousa
- Department of Gastroenterology, Hospital São Teotónio – Unidade Local de Saúde Dão Lafões, Viseu, Portugal
| | - Javier P Gisbert
- Department of Gastroenterology, Inflammatory Bowel Disease Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Mette Julsgaard
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Centre for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | | | - María Chaparro
- Department of Gastroenterology, Inflammatory Bowel Disease Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| |
Collapse
|
|
2
|
Guinn D, Kratz K, Baisden K, Ridge S, McClymont S, Fletcher EP, Johnson T, Wang Y. On placental and lactational transfer of IgG-based therapeutic proteins - Current understanding and knowledge gaps from a clinical pharmacology perspective. Clin Transl Sci 2024; 17:e70049. [PMID: 39436322 PMCID: PMC11495133 DOI: 10.1111/cts.70049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/02/2024] [Accepted: 10/03/2024] [Indexed: 10/23/2024] Open
Abstract
Maternal medication use may expose the developing fetus through placental transfer or the infant through lactational transfer. Because pregnant and lactating individuals have been historically excluded from early drug development trials, there is often limited to no human data available to inform pharmacokinetics (PK) and safety in these populations at the time of drug approval. We describe the known mechanisms of placental or lactational transfer of IgG-based therapeutic proteins and use clinical examples to highlight the potential for fetal or infant exposure during pregnancy and lactation. Placental transfer of IgG-based therapeutic proteins may result in systemic exposure to the developing fetus. A lactational transfer may be associated with local gastrointestinal (GI) exposure in the infant and may also result in systemic exposure, although data are very limited as proteins have shown instability in the GI tract. Understanding of PK and pharmacodynamic (PD) effects of IgG-based therapeutic proteins in infants exposed in utero as well as the potential exposure through human milk and its clinical implications is critical for developing treatment strategies for pregnant or lactating individuals. We share the current knowledge gaps and considerations for future evaluations to inform PK, PD, and the safety of IgG-based therapeutic proteins for safe use during pregnancy and lactation. With the increasing use of IgG-based therapeutic proteins in treating chronic diseases during pregnancy and lactation, there is a need to improve the quantity and quality of data to inform the safe use in pregnant and lactating individuals.
Collapse
Affiliation(s)
- Daphne Guinn
- Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and ResearchUS Food and Drug AdministrationSilver SpringMarylandUSA
| | - Katherine Kratz
- Division of Pediatrics and Maternal Health, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringMarylandUSA
| | - Kristie Baisden
- Division of Pediatrics and Maternal Health, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringMarylandUSA
| | - Sarah Ridge
- Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and ResearchUS Food and Drug AdministrationSilver SpringMarylandUSA
| | - Sonaly McClymont
- Division of Pediatrics and Maternal Health, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringMarylandUSA
| | - Elimika Pfuma Fletcher
- Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and ResearchUS Food and Drug AdministrationSilver SpringMarylandUSA
| | - Tamara Johnson
- Division of Pediatrics and Maternal Health, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringMarylandUSA
| | - Yow‐Ming Wang
- Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and ResearchUS Food and Drug AdministrationSilver SpringMarylandUSA
| |
Collapse
|
|
3
|
Tanaka T, Hirano D, Ishimaru S, Arataki K. A Case of Ulcerative Colitis During Pregnancy and Childbirth at an Older Age While on Biologic Therapy. Cureus 2024; 16:e66689. [PMID: 39262531 PMCID: PMC11389652 DOI: 10.7759/cureus.66689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2024] [Indexed: 09/13/2024] Open
Abstract
There is considerable uncertainty regarding the safety and efficacy of biological therapies during pregnancy. We report a case of a 46-year-old female, diagnosed with ulcerative colitis over 30 years ago, who was successfully managed with infliximab and ustekinumab. She experienced no exacerbation of her condition during two pregnancies, demonstrating the safety of biologic therapy in maintaining disease remission during pregnancy. This case report highlights successful outcomes despite the uncertainties associated with biologic therapy during pregnancy and includes a brief review of the relevant literature.
Collapse
Affiliation(s)
- Tomotaka Tanaka
- Department of Gastroenterology, Tsuchiya General Hospital, Hiroshima, JPN
| | - Daiki Hirano
- Department of Gastroenterology, Tsuchiya General Hospital, Hiroshima, JPN
| | - Syohei Ishimaru
- Department of Gastroenterology, Tsuchiya General Hospital, Hiroshima, JPN
| | - Keiko Arataki
- Department of Gastroenterology, Tsuchiya General Hospital, Hiroshima, JPN
| |
Collapse
|
|
4
|
van Gendt J, Emaus R, Visschedijk MC, Touw DJ, Bouwknegt DG, de Leeuw K, Prins JR, Malik P, Mian P. Pharmacokinetics of Monoclonal Antibodies Throughout Pregnancy: A Systematic Literature Review. Clin Pharmacokinet 2024; 63:589-622. [PMID: 38583128 PMCID: PMC11106164 DOI: 10.1007/s40262-024-01370-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND AND OBJECTIVE Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy. METHODS A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available. RESULTS A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state. CONCLUSION Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.
Collapse
Affiliation(s)
- J van Gendt
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - R Emaus
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - M C Visschedijk
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - D J Touw
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Department of Pharmaceutical Analysis, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands
| | - D G Bouwknegt
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - K de Leeuw
- Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - J R Prins
- Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - P Malik
- Calico Life Sciences, South San Francisco, USA
| | - Paola Mian
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
| |
Collapse
|
|
5
|
Lin S, Xu Z, Lin Z, Xie B, Feng J. Advances in pathogenesis and treatment of ocular involvement in Behcet's disease. Front Immunol 2023; 14:1206959. [PMID: 37841268 PMCID: PMC10570607 DOI: 10.3389/fimmu.2023.1206959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 09/08/2023] [Indexed: 10/17/2023] Open
Abstract
Behcet's disease (BD) is a chronic multi-systemic disease characterized by relapsing-remitting oral ulcers, genital ulcers, ocular inflammatory involvements, and numerous other systemic features. Ocular involvements are quite common in BD and may cause severe tissue damage and potentially blindness. Even though the pathogenesis of BD remains ambiguous, growing evidences have shown that genetic factors, environmental triggers and immunological abnormalities play significant roles in its development and progression. Novel biotherapies targeting IFN-γ, TNF-α and interleukins have been used in recent years. In this review, we mainly pay attention to the ocular involvement of BD, and discuss the current understanding of mechanisms and advances in therapeutic approaches, especially novel biologics. Finally, we discuss the management in patients with pregnancy.
Collapse
Affiliation(s)
- Suibin Lin
- Department of Gynaecology and Obstetrics, Zhangpu Hospital, Zhangzhou, China
| | - Zhirong Xu
- Department of Internal Medicine, Zhangpu Hospital, Zhangzhou, China
| | - Zhiming Lin
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Baozhao Xie
- Department of Rheumatology and Immunology, the Seventh Affiliated Hospital of Guangxi Medical University (Wuzhou Gongren Hospital), Wuzhou, China
| | - Junmei Feng
- Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Rheumatology and Immunology, Nanfang Hospital of Southern Medical University, Guangzhou, China
| |
Collapse
|
|
6
|
Torres J, Chaparro M, Julsgaard M, Katsanos K, Zelinkova Z, Agrawal M, Ardizzone S, Campmans-Kuijpers M, Dragoni G, Ferrante M, Fiorino G, Flanagan E, Gomes CF, Hart A, Hedin CR, Juillerat P, Mulders A, Myrelid P, O'Toole A, Rivière P, Scharl M, Selinger CP, Sonnenberg E, Toruner M, Wieringa J, Van der Woude CJ. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023; 17:1-27. [PMID: 36005814 DOI: 10.1093/ecco-jcc/jjac115] [Citation(s) in RCA: 121] [Impact Index Per Article: 60.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Indexed: 02/02/2023]
Affiliation(s)
- Joana Torres
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - María Chaparro
- Department of Gastroenterology, Hospital Universitario de La Princesa, IIS-Princesa, UAM, CIBEREHD, Madrid, Spain
| | - Mette Julsgaard
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Zuzana Zelinkova
- Department of Internal Medicine, Svet zdravia, Nemocnica Dunajska Streda, Slovakia
- Firstst Department of Internal Medicine of University Hospital and Slovak Medical University in Bratislava, Bratislava, Slovakia
| | - Manasi Agrawal
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Sandro Ardizzone
- Gastrointestinal Unit, Department of Biomedical and Clinical Sciences. University of Milan, Milan, Italy
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy
- Gastroenterology Department, Careggi University Hospital, Florence, Italy
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Gionata Fiorino
- Department of Gastroenterology and Digestive Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Emma Flanagan
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia
| | | | - Ailsa Hart
- Inflammatory Bowel Diseases Unit, St Mark's Hospital, Harrow, UK
| | - Charlotte Rose Hedin
- Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden
- Karolinska University Hospital, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden
| | - Pascal Juillerat
- Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
- Crohn's and Colitis Center, Gastroenterology Beaulieu SA, Lausanne, Switzerland
| | - Annemarie Mulders
- Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Pär Myrelid
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Aoibhlinn O'Toole
- Beaumont Hospital, Department of Gastroenterology, Royal College of Surgeons, Dublin, Ireland
| | - Pauline Rivière
- Gastroenterology Unit, Bordeaux University Hospital, Pessac, France
| | - Michael Scharl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Elena Sonnenberg
- Charité-Universitätsmedizin Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Germany
| | - Murat Toruner
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Jantien Wieringa
- Department of Paediatrics, Haaglanden Medical Center, The Hague, The Netherlands
- Department of Paediatrics, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - C Janneke Van der Woude
- Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| |
Collapse
|
|
7
|
Donovan B, Spiel M. Inflammatory Bowel Disease in the Childbearing Adult and Newborn. Neoreviews 2023; 24:10-23. [PMID: 36587009 DOI: 10.1542/neo.24-1-e10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Inflammatory bowel disease (IBD) often affects people in their childbearing years and has implications for pregnancy outcomes, particularly as related to increased risk of preterm delivery and effects of immunosuppressive medications on the fetus. Ideally, people with IBD should attempt conception at a time when their disease is in remission to optimize pregnancy outcomes and reduce risks of flares. Generally, pregnant individuals should continue immunosuppressive medications throughout gestation in an attempt to control the disease. Maternal risks of IBD in pregnancy include exacerbated anemia, disease flare, cesarean delivery, and treatment risks. Fetal and neonatal risks include preterm birth, low birthweight, and medication exposures. There are too few clinical trials that include pregnant or breastfeeding patients to analyze the risk/benefit profile of immunosuppressive medications for IBD treatment during pregnancy, limiting the amount of data available to guide medical treatment in this population. More studies are needed on IBD therapies, particularly as more biologics are developed and become the mainstay of treatment. Neonatal clinicians should be aware of in utero medication exposure to help guide decisions regarding newborn care.
Collapse
Affiliation(s)
- Bridget Donovan
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA
| | - Melissa Spiel
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA
| |
Collapse
|
|
8
|
Kawamoto A, Fujii T, Mitani R, Suzuki Y, Yauchi T, Okamoto R. Serum Levels of Infliximab Biosimilar in a Child Delivered From a Mother Treated for Ulcerative Colitis. Inflamm Bowel Dis 2022; 28:1298-1299. [PMID: 35700275 DOI: 10.1093/ibd/izac111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Indexed: 12/09/2022]
Abstract
Lay Summary
The infliximab biosimilar CT-P13 is used for the treatment of ulcerative colitis. We report for the first time the serum drug levels and long-term health status of the child of a patient treated with CT-P13 throughout her pregnancy.
Collapse
Affiliation(s)
- Ami Kawamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Gastroenterology, Soka Municipal Hospital, Soka City, Japan
| | - Ryuji Mitani
- Department of Obstetrics and Gynecology, Yoshinogawa Medical Center, Yoshinogawa City, Japan
| | - Yasuhiro Suzuki
- Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima City, Japan
| | - Tsunehito Yauchi
- Department of Gastroenterology, Soka Municipal Hospital, Soka City, Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| |
Collapse
|
|
9
|
Ogawa E, Goto H, Ushimaru H, Matsuo A, Takeda S, Nishimura R, Hondo T, Takahashi T. Vaginal delivery after improvement in COVID-19 by monoclonal antibody treatment: A case report and literature review. J Infect Chemother 2022; 28:982-986. [PMID: 35288022 PMCID: PMC8898669 DOI: 10.1016/j.jiac.2022.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/21/2022] [Accepted: 02/24/2022] [Indexed: 01/12/2023]
Abstract
As the COVID-19 pandemic persists, pregnant women have been increasingly affected worldwide. Women during the last trimester of pregnancy are susceptible to severe COVID-19, and there are many challenges towards its treatment. Monoclonal antibody treatment (MAT) is approved for COVID-19 patients to reduce disease severity. However, there are few reports on the MAT in perinatal women. Herein, we report a 39-year-old pregnant female (36 weeks and 6 days of gestation) with improvement in COVID-19 pneumonia after treatment with casiribimab/imdevimab, resulting in successful vaginal delivery (a 2.868 kg male newborn), along with a literature review. Early diagnosis and treatment of pregnant women with COVID-19 are important. Infectious diseases doctors and/or obstetricians should be aware of the MAT option administered to perinatal COVID-19 women to reduce disease severity.
Collapse
Affiliation(s)
- Eisuke Ogawa
- Department of Rheumatology, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan,Department of Internal Medicine, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan,Corresponding author. Departments of Rheumatology and Internal Medicine, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Hirohisa Goto
- Department of General Medicine, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Hiroyasu Ushimaru
- Department of Internal Medicine, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Akemi Matsuo
- Department of Internal Medicine, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Satoshi Takeda
- Department of Obstetrics and Gynecology, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Ryohei Nishimura
- Department of Obstetrics and Gynecology, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Takaaki Hondo
- Department of Obstetrics and Gynecology, Minami-Nagano Medical Center, Shinonoi General Hospital, 666-1 Shinonoi, Nagano-city, Nagano, 388-8004, Japan
| | - Takashi Takahashi
- Laboratory of Infectious Diseases, Graduate School of Infection Control Sciences & Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan
| |
Collapse
|
|
10
|
The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease-A Systematic Literature Review. Pharmaceutics 2022; 14:pharmaceutics14061241. [PMID: 35745812 PMCID: PMC9227141 DOI: 10.3390/pharmaceutics14061241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/27/2022] [Accepted: 06/06/2022] [Indexed: 11/19/2022] Open
Abstract
Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab. The studies for mesalazine, ustekinumab and golimumab did not provide enough data to demonstrate an effect of pregnancy on concentration and PK parameters. Therefore, no evidence-based dosing advice was given. The 6-thioguanine nucleotide levels decreased during pregnancy to 61% compared to pre-pregnancy levels. The potentially toxic metabolite 6-methylmercaptopurine (6-MMP) increased to maximal 209% of the pre-pregnancy levels. Although the PK of the thiopurines changed throughout pregnancy, no evidence-based dosing advice was provided. One study suggested that caution should be exercised when the thiopurine dose is adjusted, due to shunting 6-MMP levels. For the biologicals, infliximab levels increased, adalimumab stayed relatively stable and vedolizumab levels tended to decrease during pregnancy. Although the PK of the biologicals changed throughout pregnancy, no evidence-based dosing advice for biologicals was provided. Other drugs retrieved from the literature search were mesalazine, ustekinumab and golimumab. We conclude that limited studies have been performed on PK parameters during pregnancy for drugs used in IBD. Therefore, more extensive research to determine the values of PK parameters is warranted. After gathering the PK data, evidence-based dosing regimens can be developed.
Collapse
|
|
11
|
Abstract
Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.
Collapse
|
|
12
|
Bucur Ș, Savu AP, Stănescu AMA, Șerban ED, Nicolescu AC, Constantin T, Bobircă A, Constantin MM. Oversight and Management of Women with Psoriasis in Childbearing Age. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:780. [PMID: 35744043 PMCID: PMC9227010 DOI: 10.3390/medicina58060780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 05/31/2022] [Accepted: 06/04/2022] [Indexed: 11/16/2022]
Abstract
Psoriasis is a complex disease with many associated comorbidities, all of which have a negative impact on a patient's personal, social, and sexual life. There are some unique considerations in the effects of this disease among women. The average age of diagnosis in women with psoriasis is 28 years, and this onset corresponds to the fertile life of women. There is conflicting information about the effects of psoriasis on female fertility. Some studies suggest that this condition's associated comorbidities, personal behaviors, and reduced ovarian reserve, especially due to chronic inflammation, affect women's fertility. Another possible reason women with psoriasis are less likely to become pregnant is that their sexual intercourse frequency decreases after the condition's onset. The available information on the effects of pregnancy on women with psoriasis is limited. According to current evidence, most women will experience an improvement in their skin condition. Studies show that patients with moderate-to-severe psoriasis are more prone to experience pregnancy complications. The management of pregnant and lactating women with psoriasis is also difficult, as the safety profile of commonly used drugs in patients with psoriasis is not entirely known.
Collapse
Affiliation(s)
- Ștefana Bucur
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (Ș.B.); (A.-C.N.); (T.C.); (A.B.); (M.-M.C.)
| | | | - Ana Maria Alexandra Stănescu
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (Ș.B.); (A.-C.N.); (T.C.); (A.B.); (M.-M.C.)
| | - Elena-Daniela Șerban
- 2nd Department of Dermatology, Colentina Clinical Hospital, 020125 Bucharest, Romania;
| | - Alin-Codruț Nicolescu
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (Ș.B.); (A.-C.N.); (T.C.); (A.B.); (M.-M.C.)
- Roma Medical Center for Diagnosis and Treatment, 011773 Bucharest, Romania
| | - Traian Constantin
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (Ș.B.); (A.-C.N.); (T.C.); (A.B.); (M.-M.C.)
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050659 Bucharest, Romania
| | - Anca Bobircă
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (Ș.B.); (A.-C.N.); (T.C.); (A.B.); (M.-M.C.)
- Department of Internal Medicine and Rheumatology, “Dr. I. Cantacuzino” Hospital, 073206 Bucharest, Romania
| | - Maria-Magdalena Constantin
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (Ș.B.); (A.-C.N.); (T.C.); (A.B.); (M.-M.C.)
- 2nd Department of Dermatology, Colentina Clinical Hospital, 020125 Bucharest, Romania;
| |
Collapse
|
|
13
|
The impact of gender and sex in psoriasis: What to be aware of when treating women with psoriasis. Int J Womens Dermatol 2022; 8:e010. [PMID: 35619672 PMCID: PMC9112394 DOI: 10.1097/jw9.0000000000000010] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 02/02/2022] [Indexed: 12/25/2022] Open
Abstract
Psoriasis is a common chronic inflammatory skin disease with an exceptionally high burden for women.
Collapse
|
|
14
|
Carnovale C, Parisi F, Battini V, Zavatta A, Cheli S, Cattaneo D, Gringeri M, Mosini G, Guarnieri G, Cammarata G, Cetin I. The use of biological agents in pregnant women affected by autoimmune disorders: Why we need more research of this neglected area. Pharmacol Res 2021; 171:105786. [PMID: 34314858 DOI: 10.1016/j.phrs.2021.105786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/12/2021] [Accepted: 07/22/2021] [Indexed: 11/20/2022]
Abstract
Women of childbearing age are largely affected by several autoimmune disorders (the estimates range between 1.5 and 10 per 10,000). The increasing number of effective biological agents has dramatically revolutionized the treatment of these clinical conditions, ameliorating the patient's quality of life. The use of these agents by women during pregnancy is growing to ensure the disease activity control and avoid adverse health outcomes. However, for many newer biological agents, the degree of information concerning their use in pregnancy is often incomplete to perform a conclusive risk assessment on fetal and maternal health given the exclusion of this specific population from pharmacological clinical trials. More recently, the COVID-19 pandemic has confirmed the unacceptable inequities of pharmacological research and medical treatment for pregnant and lactating women, exacerbating the need for filling the gaps of quantitative and qualitative pharmacology data in this sensitive population. ere we summarize (i) what is already known about safety and effectiveness of biological agents in this understudied population (with specific focus on pregnancy-related health outcomes), and what we are going to learn from the on-going studies among pregnant women treated with biological agents; (ii) the methodological and ethical considerations that characterize the pharmacological research in pregnancy, also discussing emerging evidence on the use of therapeutic drug monitoring (TDM) in this clinical setting.
Collapse
Affiliation(s)
- Carla Carnovale
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy.
| | - Francesca Parisi
- Department of Woman, Mother and Neonate, "V. Buzzi" Children Hospital, ASST Fatebenefratelli Sacco, 20141 Milan, Italy
| | - Vera Battini
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy
| | - Alice Zavatta
- Department of Woman, Mother and Neonate, "V. Buzzi" Children Hospital, ASST Fatebenefratelli Sacco, 20141 Milan, Italy
| | - Stefania Cheli
- Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy
| | - Dario Cattaneo
- Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy
| | - Michele Gringeri
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy
| | - Giulia Mosini
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy
| | - Greta Guarnieri
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy
| | - Gianluca Cammarata
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Milan, Italy
| | - Irene Cetin
- Department of Woman, Mother and Neonate, "V. Buzzi" Children Hospital, ASST Fatebenefratelli Sacco, 20141 Milan, Italy; Department of Biomedical and Clinical Sciences, "Luigi Sacco", University of Milan, 20157 Milan, Italy
| |
Collapse
|
|
15
|
Bosshard N, Zbinden A, Eriksson KK, Förger F. Rituximab and Canakinumab Use During Lactation: No Detectable Serum Levels in Breastfed Infants. Rheumatol Ther 2021; 8:1043-1048. [PMID: 33999372 PMCID: PMC8217349 DOI: 10.1007/s40744-021-00313-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 04/22/2021] [Indexed: 12/18/2022] Open
Abstract
Introduction In breastfeeding patients with chronic inflammatory rheumatic diseases, a postpartum flare may require the use of biologics. However, data on the safety of biologics during lactation are scarce, potentially impeding the decision-making process. Case series We report two cases of women in whom treatment with a monoclonal IgG antibody (rituximab or canakinumab) was indicated during the lactation period. In both cases, breastfeeding was continued, and drug levels in the mother’s serum, in serial breast milk samples and in the infant’s serum were measured. Both rituximab and canakinumab showed minimal drug concentrations in breast milk and no detectable levels in the infants’ sera. Conclusion The lack of detectable levels of rituximab and canakinumab in the sera of breastfed infants reflects the poor oral bioavailability of these biologics and helps to promote their use in breastfeeding patients.
Collapse
Affiliation(s)
- Nicole Bosshard
- Department of Rheumatology and Immunology, University Hospital-University of Bern, Bern, Switzerland.
| | - Astrid Zbinden
- Department of Rheumatology and Immunology, University Hospital-University of Bern, Bern, Switzerland
| | - Klara Kristin Eriksson
- Department of Rheumatology and Immunology, University Hospital-University of Bern, Bern, Switzerland
| | - Frauke Förger
- Department of Rheumatology and Immunology, University Hospital-University of Bern, Bern, Switzerland.
| |
Collapse
|
|
16
|
LaHue SC, Anderson A, Krysko KM, Rutatangwa A, Dorsey MJ, Hale T, Mahadevan U, Rogers EE, Rosenstein MG, Bove R. Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2020; 7:e769. [PMID: 32461351 PMCID: PMC7286664 DOI: 10.1212/nxi.0000000000000769] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 04/23/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. METHODS We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. RESULTS Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. CONCLUSIONS The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.
Collapse
Affiliation(s)
- Sara C LaHue
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Annika Anderson
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Kristen M Krysko
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Alice Rutatangwa
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Morna J Dorsey
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Thomas Hale
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Uma Mahadevan
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Elizabeth E Rogers
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Melissa G Rosenstein
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA
| | - Riley Bove
- From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA.
| |
Collapse
|
|
17
|
Louchet M, Sibiude J, Peytavin G, Picone O, Tréluyer JM, Mandelbrot L. Placental transfer and safety in pregnancy of medications under investigation to treat coronavirus disease 2019. Am J Obstet Gynecol MFM 2020; 2:100159. [PMID: 32838264 PMCID: PMC7308040 DOI: 10.1016/j.ajogmf.2020.100159] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/02/2020] [Accepted: 06/07/2020] [Indexed: 12/15/2022]
Abstract
Objective Treatment of coronavirus disease 2019 is mostly symptomatic, but a wide range of medications are under investigation against severe acute respiratory syndrome coronavirus 2. Although pregnant women are excluded from clinical trials, they will inevitably receive therapies whenever they seem effective in nonpregnant patients and even under compassionate use. Methods We conducted a review of the literature on placental transfer and pregnancy safety data of drugs under current investigation for coronavirus disease 2019. Results Regarding remdesivir, there are no data in pregnant women. Several other candidates already have safety data in pregnant women, because they are repurposed drugs already used for their established indications. Thus, they may be used in pregnancy, although their safety in the context of coronavirus disease 2019 may differ from conventional use. These include HIV protease inhibitors such as lopinavir/ritonavir that have low placental transfer, interferon that does not cross the placental barrier, and hydroxychloroquine or chloroquine that has high placental transfer. There are also pregnancy safety and placental transfer data for colchicine, steroids, oseltamivir, azithromycin, and some monoclonal antibodies. However, some drugs are strictly prohibited in pregnancy because of known teratogenicity (thalidomide) or fetal toxicities (renin-angiotensin system blockers). Other candidates including tocilizumab, other interleukin 6 inhibitors, umifenovir, and favipiravir have insufficient data on pregnancy outcomes. Conclusion In life-threatening cases of coronavirus disease 2019, the potential risks of therapy to the fetus may be more than offset by the benefit of curing the mother. Although preclinical and placental transfer studies are required for a number of potential anti-severe acute respiratory syndrome coronavirus 2 drugs, several medications can already be used in pregnant women.
Collapse
Affiliation(s)
- Margaux Louchet
- Assistance Publique-Hôpitaux de Paris, Service de Gynécologie-Obstétrique, Hôpital Louis Mourier, Colombes, France
| | - Jeanne Sibiude
- Assistance Publique-Hôpitaux de Paris, Service de Gynécologie-Obstétrique, Hôpital Louis Mourier, Colombes, France
- Inserm Infection, Antimicrobials, Modelling, Evolution U1137, Paris, France
- Université de Paris, Paris, France
| | | | - Olivier Picone
- Assistance Publique-Hôpitaux de Paris, Service de Gynécologie-Obstétrique, Hôpital Louis Mourier, Colombes, France
- Inserm Infection, Antimicrobials, Modelling, Evolution U1137, Paris, France
- Université de Paris, Paris, France
| | - Jean-Marc Tréluyer
- Université de Paris, Paris, France
- Assistance Publique-Hôpitaux de Paris, Service de Pharmacologie-Toxicologie, Hôpital Bichat, Paris, France; and Assistance Publique-Hôpitaux de Paris, URC/CIC Cochin-Necker, Paris, France
| | - Laurent Mandelbrot
- Assistance Publique-Hôpitaux de Paris, Service de Gynécologie-Obstétrique, Hôpital Louis Mourier, Colombes, France
- Inserm Infection, Antimicrobials, Modelling, Evolution U1137, Paris, France
- Université de Paris, Paris, France
- Corresponding author: Laurent Mandelbrot, MD.
| |
Collapse
|
|
18
|
Wieringa JW, van der Woude CJ. Effect of biologicals and JAK inhibitors during pregnancy on health-related outcomes in children of women with inflammatory bowel disease. Best Pract Res Clin Gastroenterol 2019; 44-45:101665. [PMID: 32359679 DOI: 10.1016/j.bpg.2019.101665] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/14/2019] [Accepted: 12/26/2019] [Indexed: 02/06/2023]
Abstract
Current guidelines advise to maintain immunomodulators and biologicals in pregnant patients because relapse of inflammatory bowel is associated with unfavourable pregnancy outcome. With the exception of Methotrexate, IBD therapy seems not to be related to an increase of congenital malformations or infections requiring hospitalisation of the babies, although the effect the on the developing immune system of the exposed infants remains unknown. In this review we will focus on the effect of IBD drugs on health-related outcomes in children taking into account possible long-term effects of biologicals and immunomodulators, which are transferred across the placenta.
Collapse
Affiliation(s)
- J W Wieringa
- Department of Pediatrics, Haaglanden Medical Center and Department of Pediatrics, Subdivision of Infectious Diseases and Immunology, Erasmus MC University Medical Center-Sophia Children's Hospital, Rotterdam, Lijnbaan 32, CK The Hague, 2501, the Netherlands.
| | - C J van der Woude
- Department of Gastroenterology, Erasmus MC University Medical Center, 's Gravendijkwal 230, 3015, CE, Rotterdam, the Netherlands.
| |
Collapse
|
|
19
|
Soh MC, Moretto M. The use of biologics for autoimmune rheumatic diseases in fertility and pregnancy. Obstet Med 2019; 13:5-13. [PMID: 32284726 DOI: 10.1177/1753495x19841799] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 03/10/2019] [Indexed: 12/18/2022] Open
Abstract
In an age where autoimmune rheumatic diseases are successfully managed with biologics, their discontinuation in pregnancy is inadvisable without careful forethought; maternal disease activity is associated with adverse pregnancy outcomes, which has long-term implications for both mother and offspring. We aim to provide clinicians with the necessary tools to facilitate decision-making - when a biologic should be used, when it can be discontinued in pregnancy if appropriate. The pathophysiology of these biologic molecules and their effect on fertility, pregnancy and parturition are discussed. A summary of the 2016 international guidelines (European League Against Rheumatism and British Society in Rheumatology) on biologics in pregnancy has been tabulated; more recent publications are discussed in depth. Data on transplacental-transfer ratios and breastmilk excretion rates are also included. Biologic effects on organogenesis, their implications for the exposed infant in terms of infection risks and vaccination requirements are included, and future directions for research proposed.
Collapse
Affiliation(s)
- May Ching Soh
- Department of Rheumatology, Tauranga Hospital, Bay of Plenty District Health Board, Tauranga, New Zealand.,Department of Obstetrics and Gynaecology, Elizabeth Rothwell Building, Waikato Hospital, Waikato District Health Board, Hamilton, New Zealand.,Women's Health Academic Centre, King's College London, London, UK
| | - Marcelo Moretto
- Department of Gynaecology, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.,Clínica Generar-Human Reproduction, Porto Alegre, Brazil
| |
Collapse
|
|
20
|
Shannahan SE, Erlich JM, Peppercorn MA. Insights into the treatment of inflammatory bowel disease in pregnancy. Therap Adv Gastroenterol 2019; 12:1756284819852231. [PMID: 31191713 PMCID: PMC6540496 DOI: 10.1177/1756284819852231] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Accepted: 04/17/2019] [Indexed: 02/04/2023] Open
Abstract
Patients diagnosed with inflammatory bowel disease (IBD) are most commonly diagnosed in late adolescence or early adulthood, with half of patients being diagnosed before age 32, thus impacting peak years of reproduction and family planning. While controlled IBD has no negative effects on the ability to conceive, there is overall a trend towards voluntary childlessness due to patients' concerns for adverse fetal outcomes from underlying IBD and from adverse medication effects. Active disease at the time of conception is associated with worsening disease activity during pregnancy and carries a higher risk of poor fetal outcomes. It is therefore important to maintain remission during pregnancy, which is often achieved with pharmacologic therapy. The goal of this paper is to provide a comprehensive review of the current literature and safety data for pharmacologic treatment of IBD in pregnancy, in breastfeeding women, and in men planning to have children.
Collapse
Affiliation(s)
- Sarah E. Shannahan
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Jonathan M. Erlich
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Mark A. Peppercorn
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
21
|
Berkhout A, Clark JE, Wen SCH. In utero exposure to biologic disease-modifying anti-rheumatic drugs and effects to the infant: infectious complications, vaccine response, and safety of live vaccine administration. Expert Rev Vaccines 2019; 18:495-504. [PMID: 30916600 DOI: 10.1080/14760584.2019.1599286] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Biologic disease-modifying anti-rheumatic drugs (bDMARDS) are increasingly used in clinical practice for a variety of conditions. Due to concerns surrounding persistence of drug levels and resulting immunosuppression, current case reports recommend against live vaccine administration in the first year of life for an infant exposed to perinatal bDMARDS. As a result, this significantly impacts receipt of rotavirus vaccination, a vaccine recommended in many countries' national immunization program. Area covered: We have reviewed all available published literature to explore the effect of peripartum bDMARDS exposure on infant immune responses, safety of live vaccines, and vaccine efficacy in the first year of life. Expert opinion: We recommend that otherwise healthy newborns with a history of perinatal exposure to bDMARDS should receive rotavirus vaccinations as per the recommended schedule. Bacille Calmette et Guerin vaccine should be withheld in the first year of life. No additional booster doses of inactivated vaccines are required as they appear to mount adequate immune responses to the routine schedule.
Collapse
Affiliation(s)
- Angela Berkhout
- a Infection Management and Prevention Service, Queensland Children's Hospital , University of Queensland , Brisbane , Australia.,b The Queensland Children's Hospital , Brisbane , Australia
| | - Julia E Clark
- a Infection Management and Prevention Service, Queensland Children's Hospital , University of Queensland , Brisbane , Australia.,b The Queensland Children's Hospital , Brisbane , Australia
| | - Sophie Chien-Hui Wen
- a Infection Management and Prevention Service, Queensland Children's Hospital , University of Queensland , Brisbane , Australia.,b The Queensland Children's Hospital , Brisbane , Australia
| |
Collapse
|
|
22
|
Abstract
Many of the therapeutic options for patients with inflammatory bowel disease (IBD) suppress the immune system, which increases the risk of certain infections in these patients. Effective vaccines exist and offer protection against a number of infectious diseases. However, data has shown that IBD patients are inadequately vaccinated and, as a result, are at risk of developing certain preventable infections. Furthermore, gastroenterologists' knowledge regarding the appropriate immunizations to administer to their IBD patients is suboptimal. Areas covered: Over the past several years, there has been a considerable amount of research contributing to our knowledge regarding vaccination of patients with IBD. Expert opinion: This updated review article focuses on the current immunization schedule for the IBD patient and stresses the important role of the gastroenterologist as an active participant in the health maintenance of their IBD patients.
Collapse
Affiliation(s)
- Samantha Zullow
- a Department of Medicine, Division of Gastroenterology and Hepatology , New York University School of Medicine , New York , NY , USA
| | - Francis A Farraye
- b Department of Medicine, Section of Gastroenterology , Boston University School of Medicine , Boston , MA , USA
| |
Collapse
|
|
23
|
Tam LS, Wei JCC, Aggarwal A, Baek HJ, Cheung PP, Chiowchanwisawakit P, Dans L, Gu J, Hagino N, Kishimoto M, Reyes HM, Soroosh S, Stebbings S, Whittle S, Yeap SS, Lau CS. 2018 APLAR axial spondyloarthritis treatment recommendations. Int J Rheum Dis 2019; 22:340-356. [PMID: 30816645 DOI: 10.1111/1756-185x.13510] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 01/10/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Despite the availability of axial spondyloarthritis (SpA) recommendations proposed by various rheumatology societies, we considered that a region-specific guideline was of substantial added value to clinicians of the Asia-Pacific region, given the wide variations in predisposition to infections and other patient factors, local practice patterns, and access to treatment across countries. MATERIALS AND METHODS Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique. RESULTS Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA. CONCLUSION These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.
Collapse
Affiliation(s)
- Lai Shan Tam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Amita Aggarwal
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Han Joo Baek
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Peter P Cheung
- Division of Rheumatology, National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
| | | | - Leonila Dans
- Department of Pediatrics and Clinical Epidemiology, Philippine General Hospital, University of the Philippines, Manila, Philippines
| | - Jieruo Gu
- Department of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Noboru Hagino
- Division of Hematology and Rheumatology, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Mitsumasa Kishimoto
- Immuno-Rheumatology Center, St Luke`s International Hospital, St Luke`s International University, Tokyo, Japan
| | - Heizel Manapat Reyes
- Division of Rheumatology, Department of Medicine, Philippine General Hospital, University of the Philippines, Manila, Philippines
| | - Soosan Soroosh
- AJA University of Medical Sciences, Rheumatology Research Center, Tehran, Iran
| | - Simon Stebbings
- Department of Medicine Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
| | - Samuel Whittle
- The Queen Elizabeth Hospital, University of Adelaide, Adelaide, South Australia, Australia
| | - Swan Sim Yeap
- Department of Medicine, Subang Jaya Medical Centre, Subang Jaya, Malaysia
| | - Chak Sing Lau
- Division of Rheumatology and Clinical Immunology, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| |
Collapse
|
|
24
|
Tsao NW, Lynd LD, Sayre EC, Sadatsafavi M, Hanley G, De Vera MA. Use of biologics during pregnancy and risk of serious infections in the mother and baby: a Canadian population-based cohort study. BMJ Open 2019; 9:e023714. [PMID: 30787081 PMCID: PMC6398640 DOI: 10.1136/bmjopen-2018-023714] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES To investigate the association between exposure to biologics during pregnancy and serious infections in mothers and infants. DESIGN Retrospective cohort study. SETTING Population-based. PARTICIPANTS Women with one or more autoimmune diseases identified by International Classification of Diseases 9th/10th revision codes in healthcare administrative databases in British Columbia, Canada, who had pregnancies ending in a live or stillbirth between 1 January 2002 and 31 December 2012. Women were defined as exposed if they had at least one biologic prescription during pregnancy, and infants born to these women were considered exposed in utero. Disease-matched women with no biologics prescriptions during pregnancy, and their infants, comprised the unexposed groups. PRIMARY OUTCOME MEASURES Serious infections requiring hospitalisation. RESULTS Over the 10-year study period, there were 6218 women (8607 pregnancies) who had an autoimmune disease diagnosis, of which 90 women were exposed to biologics during pregnancy, with 100 babies born to these women. Among women exposed to biologics during pregnancy, occurrence of serious postpartum infections were low, ranging from 0% to 5%, depending on concomitant exposures to immunosuppressants. In multivariable models using logistic regression, the OR for the association of biologics exposure with serious maternal postpartum infections was 0.79 (95% CI 0.24 to 2.54). In infants exposed to biologics in utero, occurrence of serious infections during the first year of life ranged from 0% to 7%, depending on concomitant exposures to immunosuppressants in utero. Multivariable models showed no association between biologics exposure in utero and serious infant infections (OR 0.56, 95% CI 0.17 to 1.81). CONCLUSIONS These population-based data suggest that the use of biologics by women with autoimmune diseases during pregnancy is not associated with an increased risk of serious infections in mothers, during post partum or in infants during the first year of life.
Collapse
Affiliation(s)
- Nicole W Tsao
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Larry D Lynd
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
- Centre for Health Evaluation and Outcomes Sciences, Vancouver, British Columbia, Canada
| | - Eric C Sayre
- Arthritis Research Canada, Richmond, British Columbia, Canada
| | - Mohsen Sadatsafavi
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Gillian Hanley
- Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mary A De Vera
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| |
Collapse
|
|
25
|
Lee KE, Jung SA, Park SH, Moon CM, Shim SY, Kim ES, Cho SJ, Kim SE, Cho KB, Yang SK. Influence of anti-tumor necrosis factor-alpha therapy to pregnant inflammatory bowel disease women and their children's immunity. Intest Res 2019; 17:237-243. [PMID: 30727711 PMCID: PMC6505087 DOI: 10.5217/ir.2018.00071] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 11/17/2018] [Indexed: 12/11/2022] Open
Abstract
Background/Aims The onset of inflammatory bowel disease (IBD) usually occurs at young age, and therefore, women IBD patients experience pregnancy during their disease progression. Recently, the use of anti-tumor necrosis factor-α (anti-TNF-α) has been rapidly increasing. The aim of this study was to evaluate pregnancy related outcomes in women with IBD who were treated with anti-TNF-α during pregnancy and immunity of their children. Methods Korean women with IBD who had been treated with anti-TNF-α during pregnancy had been enrolled. Medical records were reviewed and a survey was performed for each patient. For the patients who agreed on additional examination for their children, children’s growth, medical history and antibody to hepatitis B surface antigen (anti-HBs) titer were checked. Results All 18 patients had been diagnosed with Crohn’s disease. There was not any case of preterm delivery, low birth-weight infant, congenital anomaly, nor stillbirth. All 12 children had followed the regular vaccination schedule for hepatitis B and 4 of them showed negative results for anti-HBs. After the 1 booster vaccination, all children demonstrated seroconversion. Regarding live vaccines, 4 children had bacillus Calmette-Guerin and 4 had rotavirus vaccine before 6 months, without any specific side effects. Conclusions This was the first study of immunity of the children born from IBD women who had been treated with anti-TNF-α medication during their pregnancy. IBD women had comparable pregnancy outcomes with the general women population, suggesting that the disease activity rather than the administered medication would be more important in healthy pregnancy. Considering the history of vaccination and anti-HBs titers, immunity seems to be intact in the children.
Collapse
Affiliation(s)
- Ko Eun Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Mo Moon
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - So Yeon Shim
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.,Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Su Jin Cho
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seong-Eun Kim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Kwang Bum Cho
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
26
|
Pham-Huy A, Sadarangani M, Huang V, Ostensen M, Castillo E, Troster SM, Vaudry W, Nguyen GC, Top KA. From mother to baby: antenatal exposure to monoclonal antibody biologics. Expert Rev Clin Immunol 2019; 15:221-229. [PMID: 30570400 DOI: 10.1080/1744666x.2019.1561282] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION More women with autoimmune and inflammatory conditions are being treated with monoclonal antibody biologics (mAbs) during their pregnancy, to maintain clinical remission. The use of anti-tumor necrosis factor alpha agents in pregnancy appears to be safe but less is known regarding other mAbs, such as anti-integrins and anti-cytokine agents. There are currently no comprehensive guidelines on how to manage the exposed infants. Areas covered: We review recent literature to assess the impact of mAbs on birth and early infant outcomes, including what is currently known about maternal and infant drug levels at birth and drug clearance in the infant. We describe the potential risks of infections and reported hematological and immunological effects of antenatal mAbs exposure on the infant and provide guidance on the management of the exposed infant. Expert opinion: Exposed infants should be monitored closely. Certain mAb exposures require specific testing and management. Safety monitoring should be done in a multidisciplinary approach and should include pediatric care providers. The current clinical experience with anti-tumor necrosis factor agents in pregnancy cannot be extrapolated to other mAbs. Long-term observational studies and a multicenter international registry are needed to better appreciate the impact of exposure, especially to newer mAbs.
Collapse
Affiliation(s)
- Anne Pham-Huy
- a Department of Pediatrics, Division of Infectious Diseases , Children's Hospital of Eastern Ontario, University of Ottawa , Ottawa , ON , Canada
| | - Manish Sadarangani
- b Vaccine Evaluation Center , BC Children's Hospital Research Institute, University of British Columbia , Vancouver , BC , Canada
| | - Vivian Huang
- c Division of Gastroenterology , Mount Sinai Hospital, University of Toronto , Toronto , ON , Canada
| | - Monika Ostensen
- d Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology , St. Olavs University Hospital , Trondheim , Norway.,e Department of Rheumatology , Sørlandet Sykehus , Kristiansand , Norway
| | - Eliana Castillo
- f Departments of Medicine and Obstetrics and Gyneacology , Cumming School of Medicine , Calgary , AB , Canada
| | - Sarah M Troster
- g Division of Rheumatology , University of Alberta , Edmonton , AB , Canada
| | - Wendy Vaudry
- h Division of infectious Diseases, Department of Pediatrics , University of Alberta, Stollery Children's Hospital , Edmonton , AB , Canada
| | - Geoffrey C Nguyen
- c Division of Gastroenterology , Mount Sinai Hospital, University of Toronto , Toronto , ON , Canada
| | - Karina A Top
- i Departments of Pediatrics and Community Health & Epidemiology , Dalhousie University , Halifax , NS , Canada
| |
Collapse
|
|
27
|
Puchner A, Gröchenig HP, Sautner J, Helmy-Bader Y, Juch H, Reinisch S, Högenauer C, Koch R, Hermann J, Studnicka-Benke A, Weger W, Puchner R, Dejaco C. 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; 131:29-44. [PMID: 30643992 PMCID: PMC6342891 DOI: 10.1007/s00508-019-1448-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 12/06/2018] [Indexed: 12/14/2022]
Abstract
An increasing and early-onset use of immunosuppressives and biologics has become more frequently seen among patients with inflammatory bowel diseases (IBD) and rheumatic disorders. Many women in their childbearing years currently receive such medications, and some of them in an interdisciplinary setting. Many questions arise in women already pregnant or wishing to conceive with respect to continuing or discontinuing treatment, the risks borne by the newborns and their mothers and long-term safety. Together with the Austrian Society of Rheumatology and Rehabilitation, the IBD working group of the Austrian Society of Gastroenterology and Hepatology has elaborated consensus statements on the use of immunosuppressives and biologics in pregnancy and lactation. This is the first Austrian interdisciplinary consensus on this topic. It is intended to serve as a basis and support for providing advice to our patients and their treating physicians.
Collapse
Affiliation(s)
- Antonia Puchner
- Division of Rheumatology, Third Medical Department, Medical University of Vienna/Vienna General Hospital, Vienna, Austria
| | - Hans Peter Gröchenig
- Medical Department, Hospital of the Brothers of Mercy, St. Veit an der Glan, Austria
| | - Judith Sautner
- Second Medical Department, Korneuburg-Stockerau Hospital/Lower Austrian Center for Rheumatology, Stockerau, Austria
| | - Yvonne Helmy-Bader
- Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
| | - Herbert Juch
- Department of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria
| | - Sieglinde Reinisch
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Christoph Högenauer
- Division of Gastroenterology and Hepatology, Medical Department, Medical University of Graz, Graz, Austria
| | - Robert Koch
- Division of Gastroenterology, First Medical Department, Medical University of Innsbruck, Innsbruck, Austria
| | - Josef Hermann
- Division of Rheumatology and Immunology, Medical Department, Medical University of Graz, Graz, Austria
| | | | - Wolfgang Weger
- Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
| | - Rudolf Puchner
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Clemens Dejaco
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
28
|
Psoriasis: Which therapy for which patient. J Am Acad Dermatol 2019; 80:43-53. [DOI: 10.1016/j.jaad.2018.06.056] [Citation(s) in RCA: 169] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 05/24/2018] [Accepted: 06/01/2018] [Indexed: 12/17/2022]
|
|
29
|
|
|
30
|
Papp KA, Haraoui B, Kumar D, Marshall JK, Bissonnette R, Bitton A, Bressler B, Gooderham M, Ho V, Jamal S, Pope JE, Steinhart AH, Vinh DC, Wade J. Vaccination Guidelines for Patients With Immune-Mediated Disorders on Immunosuppressive Therapies. J Cutan Med Surg 2018; 23:50-74. [PMID: 30463418 PMCID: PMC6330697 DOI: 10.1177/1203475418811335] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND: Patients with immune-mediated diseases on immunosuppressive therapies have more infectious episodes than healthy individuals, yet vaccination practices by physicians for this patient population remain suboptimal. OBJECTIVES: To evaluate the safety and efficacy of vaccines in individuals exposed to immunosuppressive therapies and provide evidence-based clinical practice recommendations. METHODS: A literature search for vaccination safety and efficacy in patients on immunosuppressive therapies (2009-2017) was conducted. Results were assessed using the Grading of Recommendation, Assessment, Development, and Evaluation system. RESULTS: Several immunosuppressive therapies attenuate vaccine response. Thus, vaccines should be administered before treatment whenever feasible. Inactivated vaccines can be administered without treatment discontinuation. Similarly, evidence suggests that the live zoster vaccine is safe and effective while on select immunosuppressive therapy, although use of the subunit vaccine is preferred. Caution regarding other live vaccines is warranted. Drug pharmacokinetics, duration of vaccine-induced viremia, and immune response kinetics should be considered to determine appropriate timing of vaccination and treatment (re)initiation. Infants exposed to immunosuppressive therapies through breastmilk can usually be immunized according to local guidelines. Intrauterine exposure to immunosuppressive agents is not a contraindication for inactivated vaccines. Live attenuated vaccines scheduled for infants and children ⩾12 months of age, including measles, mumps, rubella, and varicella, can be safely administered as sufficient time has elapsed for drug clearance. CONCLUSIONS: Immunosuppressive agents may attenuate vaccine responses, but protective benefit is generally maintained. While these recommendations are evidence based, they do not replace clinical judgment, and decisions regarding vaccination must carefully assess the risks, benefits, and circumstances of individual patients.
Collapse
Affiliation(s)
- Kim A Papp
- 1 K Papp Clinical Research, Waterloo, ON, Canada.,2 Probity Medical Research, Waterloo, ON, Canada
| | - Boulos Haraoui
- 3 Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Deepali Kumar
- 4 University Health Network, Toronto, ON, Canada.,5 Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - John K Marshall
- 6 Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | | | - Alain Bitton
- 8 McGill University Health Centre, Montreal, QC, Canada
| | - Brian Bressler
- 9 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,10 St Paul's Hospital, Vancouver, BC, Canada
| | - Melinda Gooderham
- 2 Probity Medical Research, Waterloo, ON, Canada.,11 Faculty of Medicine, Queen's University, Kingston, ON, Canada
| | - Vincent Ho
- 9 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Shahin Jamal
- 12 Vancouver Coastal Health, Vancouver, BC, Canada
| | - Janet E Pope
- 13 Faculty of Medicine, University of Western Ontario, London, ON, Canada.,14 St Joseph's Health Care, London, ON, Canada
| | - A Hillary Steinhart
- 5 Faculty of Medicine, University of Toronto, Toronto, ON, Canada.,15 Mount Sinai Hospital, Toronto, ON, Canada
| | - Donald C Vinh
- 8 McGill University Health Centre, Montreal, QC, Canada.,16 Research Institute, McGill University Health Centre, Montreal, QC, Canada
| | - John Wade
- 9 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.,17 Vancouver General Hospital, Vancouver, BC, Canada
| |
Collapse
|
|
31
|
Fujita H, Terui T, Hayama K, Akiyama M, Ikeda S, Mabuchi T, Ozawa A, Kanekura T, Kurosawa M, Komine M, Nakajima K, Sano S, Nemoto O, Muto M, Imai Y, Yamanishi K, Aoyama Y, Iwatsuki K. Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP. J Dermatol 2018; 45:1235-1270. [PMID: 30230572 DOI: 10.1111/1346-8138.14523] [Citation(s) in RCA: 166] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 05/25/2018] [Indexed: 05/01/2024]
Abstract
Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.
Collapse
Affiliation(s)
- Hideki Fujita
- Division of Dermatological Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Tadashi Terui
- Division of Dermatological Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Koremasa Hayama
- Division of Dermatological Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shigaku Ikeda
- Department of Dermatology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Tomotaka Mabuchi
- Department of Dermatology, Tokai University School of Medicine, Isehara, Japan
| | - Akira Ozawa
- Department of Dermatology, Tokai University School of Medicine, Isehara, Japan
| | - Takuro Kanekura
- Department of Dermatology, Kagoshima University School of Medicine, Kagoshima, Japan
| | - Michiko Kurosawa
- Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Mayumi Komine
- Department of Dermatology, Jichi Medical University, Shimotsuke, Japan
| | - Kimiko Nakajima
- Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan
| | - Shigetoshi Sano
- Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan
| | | | - Masahiko Muto
- Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan
| | - Yasutomo Imai
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kiyofumi Yamanishi
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yumi Aoyama
- Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
| | - Keiji Iwatsuki
- Department of Dermatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| |
Collapse
|
|
32
|
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; 12:811-818. [PMID: 29972674 DOI: 10.1080/17474124.2018.1496820] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Relapse of inflammatory bowel disease (IBD) during conception and pregnancy has been associated with a negative pregnancy outcome. Therefore, it is advised to maintain drugs in order to prevent relapse. The effect of drugs, which cross the placenta, on children who have been exposed during pregnancy will be discussed in this review. Areas covered: A literature search was performed using the following search terms: inflammatory bowel disease, pregnancy, infant, antitumor necrosis factor alpha, infliximab, adalimumab, golimumab, certolizumab, anti-integrins, vedolizumab, anti-interleukin (IL)-12/23 ustekinumab, placenta, vaccination. Other studies were identified by using references from articles identified through our original literature search. The occurrence of unfavorable pregnancy outcome and congenital malformations does not seem to be increased after exposure to anti-TNFα, but the effects on the developing immune system are largely unknown. For anti-integrins and anti IL-12/23, the numbers of exposed pregnancies are too small to draw any conclusions. Expert commentary: Follow-up of the developing immune system in children exposed to these drugs seems warranted, preferably in a prospective study design.
Collapse
Affiliation(s)
- Jantien W Wieringa
- a Department or Pediatrics , Haaglanden Medical Center , The Hague , The Netherlands.,b Department of Pediatric Infectious Diseases and Immunology , Erasmus Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands
| | - Gertjan J Driessen
- c Department of Pediatrics , Haga Teaching Hospital, Juliana Children's Hospital , The Hague , The Netherlands
| | | |
Collapse
|
|
33
|
Wong PKK, Bagga H, Barrett C, Hanrahan P, Johnson D, Katrib A, Leder K, Marabani M, Pentony P, Riordan J, White R, Young L. A practical approach to vaccination of patients with autoimmune inflammatory rheumatic diseases in Australia. Intern Med J 2018; 47:491-500. [PMID: 28101910 DOI: 10.1111/imj.13371] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 12/18/2016] [Accepted: 12/18/2016] [Indexed: 12/14/2022]
Abstract
Autoimmune inflammatory rheumatic diseases (AIIRD), such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are often complicated by infection, which results in significant morbidity and mortality. The increased risk of infection is probably due to a combination of immunosuppressive effects of the AIIRD, comorbidities and the use of immunosuppressive conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and more recently, targeted synthetic DMARDs and biologic DMARDs that block specific pro-inflammatory enzymes, cytokines or cell types. The use of these various DMARDs has revolutionised the treatment of AIIRD. This has led to a marked improvement in quality of life for AIIRD patients, who often now travel for prolonged periods. Many infections are preventable with vaccination. However, as protective immune responses induced by vaccination may be impaired by immunosuppression, where possible, vaccination may need to be performed prior to initiation of immunosuppression. Vaccination status should also be reviewed when planning overseas travel. Limited data regarding vaccine efficacy in patients with AIIRD make prescriptive guidelines difficult. However, a vaccination history should be part of the initial work-up in all AIIRD patients. Those caring for AIIRD patients should regularly consider vaccination to prevent infection within the practicalities of routine clinical practice.
Collapse
Affiliation(s)
- Peter K K Wong
- Mid-North Coast Arthritis Clinic, Coffs Harbour, New South Wales, Australia.,UNSW Rural Clinical School, Coffs Harbour, New South Wales, Australia
| | - Hanish Bagga
- Mid-North Coast Arthritis Clinic, Coffs Harbour, New South Wales, Australia
| | - Claire Barrett
- Department of Rheumatology, Redcliffe Hospital, Brisbane, Queensland, Australia.,Redcliffe Northside Rheumatology, Brisbane, Queensland, Australia
| | - Paddy Hanrahan
- Private Rheumatology Practice, South Perth, Western Australia, Australia.,Faculty of Medicine, University of Western Australia, South Perth, Western Australia, Australia
| | - Doug Johnson
- Department of General Medicine and Infectious Diseases, Austin Health, Melbourne, Victoria, Australia
| | - Amel Katrib
- Department of Rheumatology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Karin Leder
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.,Victorian Infectious Disease Service, Royal Melbourne Hospital at the Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Mona Marabani
- Private Rheumatology Practice, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Peta Pentony
- Mid-North Coast Arthritis Clinic, Coffs Harbour, New South Wales, Australia.,Institute of Rheumatology and Orthopaedics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - John Riordan
- Illawarra Rheumatology and University of Wollongong Graduate School of Medicine, Wollongong, New South Wales, Australia
| | - Ray White
- Private Rheumatology Practice, Sydney, New South Wales, Australia
| | - Laurel Young
- Department of Rheumatology, Redcliffe Hospital, Brisbane, Queensland, Australia.,Redcliffe Northside Rheumatology, Brisbane, Queensland, Australia
| |
Collapse
|
|
34
|
|
|
35
|
Seow CH, Leung Y, Vande Casteele N, Ehteshami Afshar E, Tanyingoh D, Bindra G, Stewart MJ, Beck PL, Kaplan GG, Ghosh S, Panaccione R. The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 45:1329-1338. [PMID: 28318043 DOI: 10.1111/apt.14040] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 01/26/2017] [Accepted: 02/21/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Transplacental transfer of infliximab and adalimumab results in detectable drug levels in the cord blood and infant. AIM To determine if pregnancy influenced the pharmacokinetics of anti-TNF agents in women with inflammatory bowel disease. METHODS Twenty-five women from the University of Calgary inflammatory bowel disease(IBD) pregnancy clinic on maintenance infliximab or adalimumab were recruited prospectively with serum bio-banking performed each trimester. Infliximab trough and adalimumab steady-state levels were the outcomes of interest and were analysed using the ANSER infliximab and adalimumab assays. Multivariate linear mixed-effects models were constructed to assess infliximab and adalimumab drug levels during pregnancy adjusting for the clinical covariates of albumin, BMI and CRP. RESULTS Fifteen women (eight Crohn's disease, seven ulcerative colitis) received infliximab and 10 women with 11 pregnancies were treated with adalimumab. Median age was 29.6 years (IQR: 27.6-31.2 years). Median disease duration was 9.2 years (IQR: 3.16-15.0 years). Median trough infliximab concentrations were 8.50 μg/mL (IQR: 7.23-10.07 μg/mL), 10.31 μg/mL (IQR: 7.66-15.63 μg/mL) and 21.02 μg/mL (IQR: 16.01-26.70 μg/mL) at trimesters 1, 2 and 3 respectively. Significant changes in albumin and BMI (P < 0.05) but not CRP (P > 0.05) were documented throughout pregnancy. After adjusting for albumin, BMI and CRP, infliximab trough levels increased during pregnancy, by 4.2 μg/mL per trimester (P = 0.02), while adalimumab drug levels remained stable (P > 0.05). CONCLUSIONS Infliximab levels rise during pregnancy, whereas adalimumab levels remain stable after accounting for changes in albumin, BMI and CRP. Therapeutic drug monitoring in the second trimester may be useful in guiding dosing in the third trimester.
Collapse
Affiliation(s)
- C H Seow
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.,Department of Community Health Sciences, University of Calgary, Calgary, Canada
| | - Y Leung
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - N Vande Casteele
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - E Ehteshami Afshar
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - D Tanyingoh
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - G Bindra
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - M J Stewart
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - P L Beck
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - G G Kaplan
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.,Department of Community Health Sciences, University of Calgary, Calgary, Canada
| | - S Ghosh
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| | - R Panaccione
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada
| |
Collapse
|
|
36
|
Treatment with biologics during pregnancy in patients with rheumatic diseases. Reumatologia 2017; 55:57-58. [PMID: 28539675 PMCID: PMC5442294 DOI: 10.5114/reum.2017.67598] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 04/10/2017] [Indexed: 11/17/2022] Open
|
|
37
|
Abstract
INTRODUCTION An increasing number of female patients with autoimmune diseases are treated with biologic drugs. Concerns in regard to safety of biologics during pregnancy arise in patients who have not completed their families. Areas covered: A review of the literature dealing with child outcomes of pregnancies exposed to biologics shows that TNF inhibitors (TNFi) are the best studied in regard to human pregnancy. In studies comparing exposed pregnancies to disease-matched controls no increased risk of spontaneous abortion, low birth weight, prematurity or congenital malformations has been observed. For rituximab, tocilizumab, anakinra, belimumab and ustekinumab no prospective, controlled studies are available, and firm conclusions about their safety during pregnancy cannot be drawn. Expert commentary: TNFi appear fairly safe when given in early pregnancy. For biologics other than TNFi prospective, controlled studies on outcomes after early and late pregnancy exposure are urgently needed. Possible effects of TNFi and all other biologics on children's immune function, infection rate and vaccination responses are either limited or absent and need to be extended. Development of laboratory tests to measure concentrations of biologics routinely in children exposed in utero would facilitate decisions in regard to the time point of vaccination with live vaccines.
Collapse
Affiliation(s)
- Monika Østensen
- a Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology , St. Olavs Hospital - Trondheim University Hospital , Norway
| |
Collapse
|
|
38
|
Abstract
While much of the existing literature in the field of reproductive rheumatology focuses on fertility, preconception counseling, and pregnancy, there is limited information regarding the postpartum period and lactation. Evidence suggests that many rheumatologic disorders flare after delivery, which, along with limitations in medications compatible with breastfeeding, make this time period challenging for women with rheumatologic conditions. This article discusses rheumatologic disease activity during the postpartum period and reviews the safety during lactation of commonly used medications for the management of rheumatic diseases. Fortunately, many of the commonly used medications are compatible with breastfeeding.
Collapse
|
|
39
|
Abstract
OPINION STATEMENT Inflammatory bowel disease is frequently diagnosed before or during key childbearing years. One of the most important factors for a healthy pregnancy is having quiescent disease prior to conception and maintaining disease remission for the duration of the pregnancy. In order to achieve that, most women will need to continue their inflammatory bowel disease (IBD) treatment during pregnancy. One of the main concerns these women have is whether these medications will have adverse effects on their growing fetus. Aminosalicylates, antibiotics, and steroids are all relatively low risk for use during pregnancy and breastfeeding. Recent studies also support the safety of continuing immunomodulators and anti-tumor necrosis factor agents during pregnancy and with breastfeeding. There seems to be an increased risk for infection, however, with use of combination therapy including both a biologic agent and an immunomodulator. Less evidence is available on the use of anti-integrins in pregnancy; however, the current data suggest they may be safe as well. Conversations about a patient's desire for pregnancy should occur between the patient and provider on a regular basis prior to conception and particularly with any change in disease activity or change in the treatment regimen. This chapter will review the current evidence on the safety of IBD medications during pregnancy and lactation so that providers can more easily discuss the importance of medication adherence for disease remission with their patients who are contemplating conception.
Collapse
|
|
40
|
Minami N, Matsuura M, Koshikawa Y, Yamada S, Honzawa Y, Yamamoto S, Nakase H. Maternal and fetal outcomes in pregnant Japanese women with inflammatory bowel disease: our experience with a series of 23 cases. Intest Res 2017; 15:90-96. [PMID: 28239318 PMCID: PMC5323313 DOI: 10.5217/ir.2017.15.1.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 08/31/2016] [Accepted: 09/05/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS Our physicians work to expand the possibilities to treat female patients with inflammatory bowel disease (IBD) who wish to become pregnant. Although many drugs, including 5-aminosalicylate (5-ASA), corticosteroids, immunomodulators, and biologics, are used safely during pregnancy, few reports have described the therapeutic regimen throughout pregnancy and the management of patients who relapse during pregnancy precisely. The aim of this study was to assess the management of patients with IBD during pregnancy. METHODS We identified 19 patients (five with Crohn's disease and 14 with ulcerative colitis [UC]) who became pregnant with a total of 23 pregnancies between May 2005 and May 2015 by reviewing the medical records of Kyoto University Hospital. The following data were collected: the maternal variables, the IBD treatment type, the disease activity, the pregnancy outcome, and the mode of delivery. RESULTS Among the 19 patients, 18 had become pregnant after being diagnosed with IBD, while one had developed UC newly after pregnancy. Throughout the gestation, all patients were treated with probiotics, 5-ASA, prednisolone, cytapheresis, or infliximab. The relapse rate during pregnancy was 21.7% (5/23 cases). The five patients who experienced a relapse were able to pursue their pregnancy after intensification of their treatments. There were no adverse fetal or neonatal problems, except in one case that required an emergency Caesarean section because of placental dysfunction and in which a very low-birth-weight infant was born preterm. CONCLUSIONS Our present data confirmed that even if the disease flares up during pregnancy, good pregnancy outcomes can be achieved with an optimal intensification of the patient's treatment.
Collapse
Affiliation(s)
- Naoki Minami
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Yorimitsu Koshikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Satoshi Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Yusuke Honzawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Shuji Yamamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| |
Collapse
|
|
41
|
Poturoglu S, Ormeci AC, Duman AE. Treatment of pregnant women with a diagnosis of inflammatory bowel disease. World J Gastrointest Pharmacol Ther 2016; 7:490-502. [PMID: 27867682 PMCID: PMC5095568 DOI: 10.4292/wjgpt.v7.i4.490] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 08/20/2016] [Accepted: 09/21/2016] [Indexed: 02/06/2023] Open
Abstract
The frequency of diagnosis of inflammatory bowel disease (IBD) has increased in younger populations. For this reason, pregnancy in patients with IBD is a topic of interest, warranting additional focus on disease management during this period. The main objective of this article is to summarize the latest findings and guidelines on the management of potential problems from pregnancy to the breastfeeding stage. Fertility is decreased in patients with active IBD. Disease remission prior to conception will likely decrease the rate of pregnancy-related complications. Most of the drugs used for IBD treatment are safe during both pregnancy and breastfeeding. Two exceptions are methotrexate and thalidomide, which are contraindicated in pregnancy. Anti-tumor necrosis factor agents are not advised during the third trimester as they exhibit increased transplacental transmission and potentially cause immunosuppression in the fetus. Radiological and endoscopic examinations and surgical interventions should be performed only when absolutely necessary. Surgery increases the fetal mortality rate. The delivery method should be determined with consideration of the disease site and presence of progression or flare up. Treatment planning should be a collaborative effort among the gastroenterologist, obstetrician, colorectal surgeon and patient.
Collapse
|
|
42
|
Shihab Z, Yeomans ND, De Cruz P. Anti-Tumour Necrosis Factor α Therapies and Inflammatory Bowel Disease Pregnancy Outcomes: A Meta-analysis. J Crohns Colitis 2016; 10:979-88. [PMID: 26755733 DOI: 10.1093/ecco-jcc/jjv234] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 12/14/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) commonly affects women during their reproductive years, leading to concerns regarding pregnancy outcomes and therapeutic safety. The aim of this study was to assess the risks associated with anti-tumour necrosis factor α (anti-TNFα) therapy for pregnancy outcomes, including rates of congenital abnormality, based on published studies. METHODS Published studies were screened from on-line databases and international meeting abstracts. A meta-analysis was performed for adverse pregnancy outcomes (APOs), congenital abnormalities (CAs), preterm birth (PTB) and low birth weight (LBW). The prevalence of CAs was compared with whole-population pooled registry data. RESULTS In women exposed to anti-TNFα the pooled odds ratio for APOs was 1.14 (95% confidence interval [CI] 0.73-1.78; p = 0.55) compared with disease-matched controls. The pooled odds ratios for CAs, PTB and LBW were 0.89 (0.37-2.13; p = 0.79), 1.21 (0.74-2.00; p = 0.45) and 1.36 (0.77-2.38; p = 0.29) respectively. The rate of CAs in TNFα-exposed women was not statistically different from that in population-wide registries (difference 0.4%, 95% CI -2.0 to +2.7). CONCLUSIONS Anti-TNFα therapy does not increase the risk of APOs, CAs, PTB or LBW compared with disease-matched controls. Furthermore, the risk of CAs is not increased when published prevalence data are compared with data for the general population. These findings may offer some reassurance for women and physicians regarding the safety profile of anti-TNFα during pregnancy in IBD.
Collapse
Affiliation(s)
- Zaid Shihab
- University of Melbourne, Melbourne, Victoria, Australia
| | - Neville D Yeomans
- University of Melbourne, Melbourne, Victoria, Australia Office for Research, Austin Health, Melbourne, Victoria, Australia
| | | |
Collapse
|
|
43
|
Levy RA, de Jesús GR, de Jesús NR, Klumb EM. Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactation. Autoimmun Rev 2016; 15:955-63. [PMID: 27490204 DOI: 10.1016/j.autrev.2016.07.014] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Accepted: 07/07/2016] [Indexed: 02/08/2023]
Abstract
The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be recommended.
Collapse
Affiliation(s)
- Roger A Levy
- Department of Rheumatology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Pós-graduação em Ciências Médicas (PGCM), Faculdade de Ciências, Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Guilherme R de Jesús
- Department of Obstetrics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Obstetrics, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil; Pós-graduação em Ciências Médicas (PGCM), Faculdade de Ciências, Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Nilson R de Jesús
- Department of Obstetrics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Evandro M Klumb
- Department of Rheumatology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Pós-graduação em Ciências Médicas (PGCM), Faculdade de Ciências, Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| |
Collapse
|
|
44
|
Sheibani S, Cohen R, Kane S, Dubinsky M, Church JA, Mahadevan U. The Effect of Maternal Peripartum Anti-TNFα Use on Infant Immune Response. Dig Dis Sci 2016; 61:1622-7. [PMID: 26725061 DOI: 10.1007/s10620-015-3992-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 12/08/2015] [Indexed: 01/11/2023]
Abstract
BACKGROUND Infliximab (IFX) and adalimumab (ADA) cross the placenta in the third trimester and can be detectable in infants for up to 12 months. AIM The aim of this study was to determine whether in utero IFX or ADA exposure results in an impaired immune response in infants, as measured by immunoglobulin levels and antibody responses to routine primary immunizations. METHODS Infants who were exposed to in utero anti-TNFα agents were prospectively evaluated. Immunoglobulin levels (IgG, IgM, IgA) and antibodies to standard vaccinations, including tetanus toxoid (tetanus) and Haemophilus influenza type b (Hib), were measured in infants of at least 6 months of age. RESULTS Twelve infants were prospectively studied: 10 exposed to in utero IFX and 2 exposed to ADA with at least one dose administered in the third trimester. Immunoglobulin levels were available on 10/12 patients, with all showing adequate immunoglobulin levels, except for low IgM levels in 5 (50 %) infants. Adequate responses to both the tetanus and Hib vaccines were seen in 11 of 12 (92 %) infants. CONCLUSIONS Infants exposed to anti-TNFα agents in utero demonstrate appropriate response to two commonly administered neonatal vaccines and show adequate immunoglobulin levels, except for IgM. Newborns with a history of exposure to anti-TNFα agents should follow a standard vaccination schedule for inactive vaccines.
Collapse
Affiliation(s)
- Sarah Sheibani
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
- Division of Gastroenterology, University of Southern California, Keck School of Medicine, 1520 San Pablo Street, Suite 1000, Los Angeles, CA, 90033-5312, USA.
| | - Russell Cohen
- Division of Gastroenterology, Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Sunanda Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Marla Dubinsky
- Division of Gastroenterology, Department of Medicine, Mt. Sinai Medical Center, New York, NY, USA
| | - Joseph A Church
- Division of Clinical Immunology and Allergy, Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Uma Mahadevan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| |
Collapse
|
|
45
|
Förger F, Villiger PM. Treatment of rheumatoid arthritis during pregnancy: present and future. Expert Rev Clin Immunol 2016; 12:937-44. [DOI: 10.1080/1744666x.2016.1184973] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
|
46
|
Krause ML, Makol A. Management of rheumatoid arthritis during pregnancy: challenges and solutions. Open Access Rheumatol 2016; 8:23-36. [PMID: 27843367 PMCID: PMC5098768 DOI: 10.2147/oarrr.s85340] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Rheumatoid arthritis, a chronic inflammatory autoimmune disease with significant physical disability, affects women three times more frequently than men, often in their childbearing years. Parenthood decisions can be challenging, often affected by perceptions of their disease state, health care needs, and complex pharmacological treatments. Many women struggle to find adequate information to guide them on pregnancy planning, lactation, and early parenting in relation to their chronic condition. The expanded availability and choice of pharmacotherapies have supported optimal disease control prior to conception and enhanced physical capabilities for women to successfully overcome the challenges of raising children but require a detailed understanding of their risks and safety in the setting of pregnancy and breastfeeding. This review outlines the various situational challenges faced by rheumatologists in providing care to men and women in the reproductive age group interested in starting a family. Up to date evidence-based solutions particularly focusing on the safe use of disease-modifying antirheumatic drugs and biologic response modifiers to assist rheumatologists in the care of pregnant and lactating women with RA are reviewed.
Collapse
Affiliation(s)
- Megan L Krause
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, MN, USA
| | - Ashima Makol
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, MN, USA
| |
Collapse
|
|
47
|
Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, Ling KL, Lim WC, Thia KT, Wei SC, Leung WK, Koh PK, Gearry RB, Goh KL, Ouyang Q, Sollano J, Manatsathit S, de Silva HJ, Rerknimitr R, Pisespongsa P, Abu Hassan MR, Sung J, Hibi T, Boey CCM, Moran N, Leong RWL. Asia-Pacific consensus statements on Crohn's disease. Part 2: Management. J Gastroenterol Hepatol 2016; 31:56-68. [PMID: 25819311 DOI: 10.1111/jgh.12958] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2015] [Indexed: 02/05/2023]
Abstract
The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field.
Collapse
Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ida Hilmi
- Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Peter R Gibson
- Monash University Department of Medicine, Box Hill Hospital, Melbourne, Victoria, Australia
| | - Kwong Ming Fock
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Khoon Lin Ling
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Wee Chian Lim
- Department of Gastroenterology, Tan Tock Seng Hospital, Singapore
| | - Kelvin T Thia
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Shu-chen Wei
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | | | - Poh Koon Koh
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Khean Lee Goh
- Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Qin Ouyang
- Division of Gastroenterology, Department of Internal Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Sathaporn Manatsathit
- Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - H Janaka de Silva
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Pises Pisespongsa
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Joseph Sung
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | | | | | - Neil Moran
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
| | - Rupert W L Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
| | | |
Collapse
|
|
48
|
Management of Inflammatory Bowel Disease during Pregnancy and Breastfeeding Varies Widely: A Need for Further Education. Can J Gastroenterol Hepatol 2016; 2016:6193275. [PMID: 27725926 PMCID: PMC5048030 DOI: 10.1155/2016/6193275] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2015] [Accepted: 08/25/2016] [Indexed: 12/16/2022] Open
Abstract
Background. Inflammatory bowel disease (IBD) affects patients in their young reproductive years. Women with IBD require maintenance therapies during pregnancy and breastfeeding. However, physician management of IBD during pregnancy and breastfeeding has not been well characterized. Objective. To characterize physician perceptions and management of IBD during pregnancy and breastfeeding. Methods. A cross-sectional survey of Canadian physicians who are involved in the care of women with IBD was conducted. The survey included multiple-choice and Likert scale questions about perceptions and practice patterns regarding the management of IBD during pregnancy and breastfeeding. Results. 183 practicing physicians completed the questionnaire: 97/183 (53.0%) gastroenterologists; 75/183 (41.0%) general practitioners; and 11/183 (6.0%) other physicians. Almost half (87/183, 47.5%) of the physicians felt comfortable managing pregnant IBD patients. For specified IBD medications, proportions of physicians who indicated they would continue them during pregnancy were as follows: sulfasalazine, 47.4%; oral mesalamine, 67.0%; topical mesalamine, 70.3%; oral prednisone, 68.0%; topical prednisone, 78.0%; oral budesonide, 61.6%; topical budesonide, 75.0%; ciprofloxacin, 15.3%; metronidazole, 31.4%; azathioprine, 57.1%; methotrexate, 2.8%; infliximab, 55.6%; adalimumab, 78.1%. Similar proportions of physicians would continue these medications during breastfeeding. A higher proportion of gastroenterologists than nongastroenterologists indicated appropriate use of these IBD medications during pregnancy and breastfeeding. Conclusions. Physician management of IBD during pregnancy and breastfeeding varies widely. Relative to other physicians, responses of gastroenterologists more frequently reflected best practices pertaining to medications for control of IBD during pregnancy and breastfeeding. There is a need for further education regarding the management of IBD during pregnancy and breastfeeding.
Collapse
|
|
49
|
Ling J, Koren G. Challenges in vaccinating infants born to mothers taking immunoglobulin biologicals during pregnancy. Expert Rev Vaccines 2015; 15:239-56. [DOI: 10.1586/14760584.2016.1115351] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Juejing Ling
- Department of Pharmaceutical Sciences, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Gideon Koren
- Department of Pharmaceutical Sciences, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada
| |
Collapse
|
|
50
|
Damas OM, Deshpande AR, Avalos DJ, Abreu MT. Treating Inflammatory Bowel Disease in Pregnancy: The Issues We Face Today. J Crohns Colitis 2015; 9:928-36. [PMID: 26129693 DOI: 10.1093/ecco-jcc/jjv118] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 06/25/2015] [Indexed: 12/12/2022]
Abstract
Many women of childbearing age are living with inflammatory bowel disease [IBD], yet there are limited studies on the use of IBD medications in pregnancy. In this review, we provide a comprehensive update on the safety of these medications during pregnancy, particularly thiopurines and biologicals. Antibiotics, steroids, and aminosalicylates are relatively low risk for use in pregnancy, and growing evidence supports the safety of immunomodulators and anti-tumour necrosis factor agents as well. Available studies on infliximab, adalimumab, and certolizumab pegol show no increase in adverse events during pregnancy or perinatally. Similarly, studies on lactation demonstrate that concentrations of subcutaneous anti-tumour necrosis factor biologicals are undetectable, and levels of thiopurines and infliximab are negligible in breast milk. Less is known about anti-integrins in pregnancy [eg natalizumab and vedolizumab] but currently available data suggest they may be safe as well. Although more studies are needed to examine the long-term effects of these medications on offspring, the available data provide reassuring information for providers caring for women of childbearing age.
Collapse
Affiliation(s)
- Oriana M Damas
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| | - Amar R Deshpande
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| | - Danny J Avalos
- University of Miami Miller School of Medicine Palm Beach Regional Campus, Internal Medicine Division, Department of Medicine, West Palm Beach, FL
| | - Maria T Abreu
- University of Miami Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL
| |
Collapse
|