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Li S, Liu H, Zeng S, Xie J, Li Z, Yang Y, Chuan J. Safety of biologics in patients with autoimmune rheumatic diseases during pregnancy: Systematic review and meta-analysis. Autoimmun Rev 2025; 24:103827. [PMID: 40339681 DOI: 10.1016/j.autrev.2025.103827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 04/29/2025] [Accepted: 05/04/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Patients with autoimmune rheumatic diseases (ARDs) face the dual challenge of controlling disease activity while ensuring fetal safety during pregnancy. Biologics are increasingly used to treat ARDs, but evidence regarding their safety during pregnancy remains uncertain. This study aims to systematically evaluate the safety of biologics during pregnancy by performing a systematic review and meta-analysis. METHODS A comprehensive search was conducted in major databases to identify studies involving pregnant ARDs patients treated with biologics from inception to 30th September 2024. The outcomes assessed included small for gestational age (SGA), cesarean section, preterm birth (PTB), low birth weight (LBW), gestational diabetes mellitus (GDM), pre-eclampsia, gestational hypertension, severe maternal infection, birth defects (BD), and a composite outcome of fetal miscarriage or death. RESULTS A total of 40 studies involving 11,712 patients were included. The pooled prevalence of adverse pregnancy outcomes (APOs) in patients exposed to biologics was comparable to those observed in the general ARDs population. Compared to other biologics, tumor necrosis factor inhibitors (TNFis) was associated with a significantly lower prevalence of cesarean section (26.93 % vs. 63.64 %, p = 0.01), early pregnancy loss (10.44 % vs. 18.77 %, p = 0.03), and termination of pregnancy (8.59 % vs. 16.11 %, p < 0.01). Compared to csDMARDs, biologic use during pregnancy did not significantly increase the risk of APOs. CONCLUSION Exposure to biologics during pregnancy in ARDs patients does not significantly increase the risk of APOs, with TNFis showing a well-supported safety profile, while non-TNFi biologics may carry higher risks, requiring cautious evaluation.
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Affiliation(s)
- Shiran Li
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Hongxi Liu
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Siyu Zeng
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Jingxian Xie
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; College of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhimin Li
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Yong Yang
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
| | - Junlan Chuan
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
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Gaio M, Vastarella MG, Sullo MG, Scavone C, Riccardi C, Campitiello MR, Sportiello L, Rafaniello C. Pregnancy Recommendations Solely Based on Preclinical Evidence Should Be Integrated with Real-World Evidence: A Disproportionality Analysis of Certolizumab and Other TNF-Alpha Inhibitors Used in Pregnant Patients with Psoriasis. Pharmaceuticals (Basel) 2024; 17:904. [PMID: 39065754 PMCID: PMC11279583 DOI: 10.3390/ph17070904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/15/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Treatment for pregnant women with psoriasis is limited by the lack of information typically related to clinical trials. While anti-tumor necrosis factor (TNF) drugs offer therapeutic benefits, their safety during pregnancy is a concern. Notably, certolizumab is comparatively safer than adalimumab, etanercept, infliximab, and golimumab according to the current recommendations. Thus, this study aimed to conduct a pharmacovigilance comparative analysis of maternal and neonatal outcomes associated with certolizumab versus other anti-TNF drugs by using data from EudraVigilance. A descriptive analysis was performed of Individual Case Safety Reports (ICSRs) associated with an anti-TNF drug and related to the pregnant patients with psoriasis from 2009 and 2023, focusing our analysis on the specific pregnancy outcomes and fetal/neonatal disorders. The most common pregnancy-related adverse event was spontaneous abortion, predominantly related to adalimumab and certolizumab. Certolizumab was also reported in cases of caesarean section, gestational diabetes, abortion, fetal death, fetal distress syndrome, pre-eclampsia, and premature separation of placenta. Generally, the findings from our study depicted a safety profile that overlapped for each anti-TNF drug, both in maternal/neonatal outcomes and other adverse events, suggesting no substantial differences between treatments. We advocate for further investigations before making concrete recommendations.
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Affiliation(s)
- Mario Gaio
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy; (C.S.); (C.R.); (L.S.); (C.R.)
- Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Maria Giovanna Vastarella
- Department of Women, Child and General and Special Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Maria Giuseppa Sullo
- AOU Policlinico, Università degli Studi della Campania “L. Vanvitelli”, 80138 Naples, Italy;
| | - Cristina Scavone
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy; (C.S.); (C.R.); (L.S.); (C.R.)
- Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Consiglia Riccardi
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy; (C.S.); (C.R.); (L.S.); (C.R.)
- Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Maria Rosaria Campitiello
- Department of Obstetrics and Gynaecology and Physiopathology of Human Reproduction, ASL Salerno, 84124 Salerno, Italy;
| | - Liberata Sportiello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy; (C.S.); (C.R.); (L.S.); (C.R.)
- Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Concetta Rafaniello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy; (C.S.); (C.R.); (L.S.); (C.R.)
- Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
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Russell MD, Dey M, Flint J, Davie P, Allen A, Crossley A, Frishman M, Gayed M, Hodson K, Khamashta M, Moore L, Panchal S, Piper M, Reid C, Saxby K, Schreiber K, Senvar N, Tosounidou S, van de Venne M, Warburton L, Williams D, Yee CS, Gordon C, Giles I, Roddy E, Armon K, Astell L, Cotton C, Davidson A, Fordham S, Jones C, Joyce C, Kuttikat A, McLaren Z, Merrison K, Mewar D, Mootoo A, Williams E, BSR Standards, Audit and Guidelines Working Group. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2022; 62:e48-e88. [PMID: 36318966 PMCID: PMC10070073 DOI: 10.1093/rheumatology/keac551] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Mark D Russell
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Mrinalini Dey
- Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Julia Flint
- Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Shropshire, UK
| | - Philippa Davie
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Alexander Allen
- Clinical Affairs, British Society for Rheumatology, London, UK
| | | | - Margreta Frishman
- Rheumatology, North Middlesex University Hospital NHS Trust, London, UK
| | - Mary Gayed
- Rheumatology, Sandwell and West Birmingham Hospitals, Birmingham, UK
| | | | - Munther Khamashta
- Lupus Research Unit, Division of Women's Health, King's College London, London, UK
| | - Louise Moore
- Rheumatic and Musculoskeletal Disease Unit, Our Lady's Hospice and Care Service, Dublin, Ireland
| | - Sonia Panchal
- Department of Rheumatology, South Warwickshire NHS Foundation Trust, Warwickshire, UK
| | - Madeleine Piper
- Royal National Hospital for Rheumatic Diseases, Royal United Hospital, Bath, UK
| | | | - Katherine Saxby
- Pharmacy, University College London Hospitals NHS Foundation Trust, London, UK
| | - Karen Schreiber
- Thrombosis and Haemostasis, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Rheumatology, Danish Hospital for Rheumatic Diseases, Sonderborg, Denmark.,Department of Regional Health Research (IRS), University of Southern Denmark, Odense, Denmark
| | - Naz Senvar
- Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Sofia Tosounidou
- Lupus UK Centre of Excellence, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | | | | | - David Williams
- Obstetrics, University College London Hospitals NHS Foundation Trust, London, UK
| | - Chee-Seng Yee
- Department of Rheumatology, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Doncaster, UK
| | - Caroline Gordon
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Ian Giles
- Centre for Rheumatology, Division of Medicine, University College London, London, UK
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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.
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5
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Actualización práctica de las recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología (GPS) para el tratamiento de la psoriasis con terapia biológica. Parte 2 «Manejo de poblaciones especiales, pacientes con comorbilidad y gestión del riesgo». ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:583-609. [DOI: 10.1016/j.ad.2022.01.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 01/26/2022] [Indexed: 12/19/2022] Open
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Carrascosa JM, Puig L, Romero IB, Salgado-Boquete L, Del Alcázar E, Lencina JJA, Moreno D, de la Cueva P. [Translated article] Practical Update of the Guidelines Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPs) on the Treatment of Psoriasis With Biologic Agents: Part 2-Management of Special Populations, Patients With Comorbid Conditions, and Risk. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:T583-T609. [PMID: 35748004 DOI: 10.1016/j.ad.2022.01.040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 01/26/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Since its inception, the Psoriasis Group (GPs) of the Spanish Academy of Dermatology and Venereology (AEDV) has worked to continuously update recommendations for the treatment of psoriasis based on the best available evidence and incorporating proposals arising from and aimed at clinical practice. An updated GPs consensus document on the treatment of moderate to severe psoriasis was needed because of changes in the treatment paradigm and the approval in recent years of a large number of new biologic agents. METHODOLOGY The consensus document was developed using the nominal group technique complemented by a scoping review. First, a designated coordinator selected a group of GPs members for the panel based on their experience and knowledge of psoriasis. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. The coordinator then drew up a set of proposed recommendations, which were discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted. RESULTS The present guidelines include updated recommendations on assessing the severity of psoriasis and criteria for the indication of systemic treatment. They also include general principles for the treatment of patients with moderate to severe psoriasis and define treatment goals for these patients as well as criteria for the indication and selection of initial and subsequent therapies Practical issues, such as treatment failure and maintenance of response, are also addressed.
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Affiliation(s)
- J M Carrascosa
- Departamento de Dermatología, Hospital Universitari Germans Trias I Pujol, Badalona, Universitat Autònoma de Barcelona, IGTP, Barcelona, Spain.
| | - L Puig
- Departamento de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - I B Romero
- Departamento de Dermatología, Hospital General Universitario de Alicante-ISABIAL - Universidad Miguel Hernández de Elche, Alicante, Spain
| | - L Salgado-Boquete
- Departamento de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - E Del Alcázar
- Departamento de Dermatología, Hospital Universitari Germans Trias I Pujol, Badalona, Universitat Autònoma de Barcelona, IGTP, Barcelona, Spain
| | - J J A Lencina
- Servicio de Dermatología, Hospital Universitario Vega Baja, Alicante, Spain
| | - D Moreno
- Departamento de Dermatología, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, Spain
| | - P de la Cueva
- Servicio de Dermatología, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain
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Balakirski G, Gerdes S, Beissert S, Ochsendorf F, von Kiedrowski R, Wilsmann-Theis D. Psoriasis-Therapie während Schwangerschaft und Stillzeit. J Dtsch Dermatol Ges 2022; 20:653-685. [PMID: 35578434 DOI: 10.1111/ddg.14789_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 03/09/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Galina Balakirski
- Zentrum für Dermatologie, Allergologie und Dermatochirurgie, HELIOS Universitätsklinikum Wuppertal, Universität Witten/Herdecke, Wuppertal
| | - Sascha Gerdes
- Psoriasis-Zentrum, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig- Holstein - Campus Kiel
| | - Stefan Beissert
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden
| | - Falk Ochsendorf
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt am Main
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8
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Balakirski G, Gerdes S, Beissert S, Ochsendorf F, von Kiedrowski R, Wilsmann-Theis D. Therapy of psoriasis during pregnancy and breast-feeding. J Dtsch Dermatol Ges 2022; 20:653-683. [PMID: 35578438 DOI: 10.1111/ddg.14789] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 03/09/2022] [Indexed: 12/21/2022]
Abstract
There have been multiple systemic drugs approved for the therapy of psoriasis vulgaris and psoriasis arthritis (PsA) in the last decade. However, treatment decisions are difficult to make in women planning a pregnancy and in pregnant and lactating women due to the paucity of data for such cases. The strongest evidence for psoriasis therapy during pregnancy exists for topical corticosteroids. Medically controlled use of UVB-therapy is also considered safe. The best evidence regarding systemic therapy during pregnancy and lactation is available for the group of TNF-alpha inhibitors, which is also reflected in the respective medical product information. This is especially important in cases of psoriatic arthritis. Among traditional systemic therapeutics, the largest clinical experience exists for ciclosporin, which, if medically necessary, may be continued during gestation. However, TNF-alpha inhibitors, especially the pegylated form, should be preferred in case of pregnancy. Furthermore, an elective pregnancy termination is not necessary due to systemic therapy of psoriasis with many further substances during the first pregnancy weeks. The current work provides a comprehensive review of the scientific literature on treatment of psoriasis during pregnancy and lactation. Based on the available scientific information, severity of psoriasis and patient's comorbidities, the best possible therapeutic approach can be found in consensus with the patient.
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Affiliation(s)
- Galina Balakirski
- Center for Dermatology, Allergology and Dermatosurgery, HELIOS University Hospital Wuppertal, Witten/Herdecke University, Wuppertal, Germany
| | - Sascha Gerdes
- Psoriasis Center, Department of Dermatology, Venereology and Allergology, University Hospital Schleswig- Holstein - Campus Kiel, Germany
| | - Stefan Beissert
- Department and Clinic for Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Falk Ochsendorf
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt am Main, Frankfurt, Germany
| | | | - Dagmar Wilsmann-Theis
- Department and Clinic for Dermatology and Allergology, University Hospital Bonn, Germany
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9
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De Felice KM, Kane S. Safety of anti-TNF agents in pregnancy. J Allergy Clin Immunol 2021; 148:661-667. [PMID: 34489011 DOI: 10.1016/j.jaci.2021.07.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis are associated with adverse pregnancy outcomes. Active maternal disease during pregnancy is associated with additional negative outcomes. Anti-TNF agents are effective treatments for inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. These agents cross the placenta starting in the second trimester, with levels detected for several months after birth. This has led to safety concerns, with continued therapy during pregnancy for both the mother and the infant. This review covers retrospective and prospective data published from various cohorts of pregnant women exposed to anti-TNF agents during pregnancy. It highlights the safety of anti-TNF drugs in pregnancy, breast-feeding, and during the first year of life of the infant.
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Affiliation(s)
- Kara M De Felice
- Department of Gastroenterology, Louisiana State University, Department of Gastroenterology, New Orleans, La.
| | - Sunanda Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minn
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Simionescu AA, Danciu BM, Stanescu AMA. State-of-the-Art Review of Pregnancy-Related Psoriasis. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:804. [PMID: 34441010 PMCID: PMC8402069 DOI: 10.3390/medicina57080804] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/14/2022]
Abstract
Psoriasis is a chronic immunologic disease involving inflammation that can target internal organs, the skin, and joints. The peak incidence occurs between the age of 30 and 40 years, which overlaps with the typical reproductive period of women. Because of comorbidities that can accompany psoriasis, including metabolic syndrome, cardiovascular involvement, and major depressive disorders, the condition is a complex one. The role of hormones during pregnancy in the lesion dynamics of psoriasis is unclear, and it is important to resolve the implications of this pathology during pregnancy are. Furthermore, treating pregnant women who have psoriasis represents a challenge as most drugs generally prescribed for this pathology are contraindicated in pregnancy because of teratogenic effects. This review covers the state of the art in psoriasis associated with pregnancy. Careful pregnancy monitoring in moderate-to-severe psoriasis vulgaris is required given the high risk of related complications in pregnancy, including pregnancy-induced hypertensive disorders, low birth weight for gestational age, and gestational diabetes. Topical corticosteroids are safe during pregnancy but effective only for localised forms of psoriasis. Monoclonal antibodies targeting cytokines specifically upregulated in psoriasis, such as ustekinumab (IL-12/23 inhibitor), secukinumab (IL-17 inhibitor) can be effective for the severe form of psoriasis during pregnancy. A multidisciplinary team must choose optimal treatment, taking into account fetal and maternal risks and benefits.
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Affiliation(s)
- Anca Angela Simionescu
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Bianca Mihaela Danciu
- Department of Obstetrics, Gynecology and Neonatology, “Dr. Alfred Rusescu” National Institute for Maternal and Child Health, 127715 Bucharest, Romania;
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Barenbrug L, Groen MT, Hoentjen F, van Drongelen J, Reek JMPAVD, Joosten I, de Jong EMGJ, van der Molen RG. Pregnancy and neonatal outcomes in women with immune mediated inflammatory diseases exposed to anti-tumor necrosis factor-α during pregnancy: A systemic review and meta-analysis. J Autoimmun 2021; 122:102676. [PMID: 34126302 DOI: 10.1016/j.jaut.2021.102676] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/27/2021] [Accepted: 05/29/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Anti-TNFα is increasingly used as treatment for immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and psoriasis (PS). However, the impact of anti-TNFα during pregnancy on mother and newborn is under debate. This requires a sound knowledge of the effects of this treatment on pregnancy and neonatal outcomes. OBJECTIVES To assess pregnancy and neonatal outcomes after anti-TNFα therapy during pregnancy in women with IMID, specifically IBD, RA and PS. METHODS We performed a systematic review and meta-analysis of 39 studies assessing pregnancy and neonatal outcomes of women with IMID exposed to anti-TNFα agents during pregnancy. We used a random-effects model to determine pooled outcome measures. RESULTS An increased risk of preterm births (OR 1.45, 95% CI = 1.16 to 1.82, p = 0.001) and infections in newborns (OR 1.12, 95% CI = 1.00 to 1.27, p = 0.05)) was seen for women in the combined group of IMID exposed to anti-TNFα compared to diseased controls. Specifically for IBD patients exposed to anti-TNFα, the risk was increased for preterm birth (OR 1.66, 95% CI = 1.14 to 2.42, p = 0.009), and low birth weight (OR 1.49, 95% CI = 1.01 to 2.20, p = 0.047) compared to diseased controls. Combined data from studies of women with RA and PS, showed no increased risk for adverse pregnancy outcome after exposure to anti-TNFα. Most children of mothers with IMID received vaccination according to national vaccination schemes and only minor adverse events were reported. CONCLUSION Exposure to anti-TNFα agents during pregnancy is associated with increased risk of preterm birth and infections in newborns of women with IMID compared to diseased controls. The risk of preterm birth and low birth weight was increased in women with IBD specifically. The increased risk of infections in newborns underlines the importance of vaccination, which seems to be safe in children exposed to anti-TNFα. Delay of vaccination is therefore unnecessary in these children. These data may aid in balancing the continuing anti-TNFα therapy versus the risk of adverse pregnancy outcomes.
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Affiliation(s)
- Liana Barenbrug
- Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Maarten Te Groen
- Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Frank Hoentjen
- Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Joris van Drongelen
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands
| | | | - Irma Joosten
- Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Elke M G J de Jong
- Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Renate G van der Molen
- Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
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12
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Prasad JD, Gunn KC, Davidson JO, Galinsky R, Graham SE, Berry MJ, Bennet L, Gunn AJ, Dean JM. Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury. Int J Mol Sci 2021; 22:4008. [PMID: 33924540 PMCID: PMC8069827 DOI: 10.3390/ijms22084008] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/09/2021] [Accepted: 04/10/2021] [Indexed: 12/13/2022] Open
Abstract
Despite the prevalence of preterm brain injury, there are no established neuroprotective strategies to prevent or alleviate mild-to-moderate inflammation-related brain injury. Perinatal infection and inflammation have been shown to trigger acute neuroinflammation, including proinflammatory cytokine release and gliosis, which are associated with acute and chronic disturbances in brain cell survival and maturation. These findings suggest the hypothesis that the inhibition of peripheral immune responses following infection or nonspecific inflammation may be a therapeutic strategy to reduce the associated brain injury and neurobehavioral deficits. This review provides an overview of the neonatal immunity, neuroinflammation, and mechanisms of inflammation-related brain injury in preterm infants and explores the safety and efficacy of anti-inflammatory agents as potentially neurotherapeutics.
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Affiliation(s)
- Jaya D. Prasad
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1010, New Zealand; (J.D.P.); (K.C.G.); (J.O.D.); (L.B.); (A.J.G.)
| | - Katherine C. Gunn
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1010, New Zealand; (J.D.P.); (K.C.G.); (J.O.D.); (L.B.); (A.J.G.)
| | - Joanne O. Davidson
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1010, New Zealand; (J.D.P.); (K.C.G.); (J.O.D.); (L.B.); (A.J.G.)
| | - Robert Galinsky
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia;
| | - Scott E. Graham
- Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1010, New Zealand;
| | - Mary J. Berry
- Department of Pediatrics and Health Care, University of Otago, Dunedin 9016, New Zealand;
| | - Laura Bennet
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1010, New Zealand; (J.D.P.); (K.C.G.); (J.O.D.); (L.B.); (A.J.G.)
| | - Alistair J. Gunn
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1010, New Zealand; (J.D.P.); (K.C.G.); (J.O.D.); (L.B.); (A.J.G.)
| | - Justin M. Dean
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1010, New Zealand; (J.D.P.); (K.C.G.); (J.O.D.); (L.B.); (A.J.G.)
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13
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Belinchón I, Velasco M, Ara-Martín M, Armesto Alonso S, Baniandrés Rodríguez O, Ferrándiz Pulido L, García-Bustinduy M, Martínez-López JA, Martínez Sánchez N, Pérez Ferriols A, Pérez Pascual E, Rivera Díaz R, Ruiz-Villaverde R, Taberner Ferrer R, Vicente Villa A, Carrascosa JM. Management of Psoriasis During Preconception, Pregnancy, Postpartum, and Breastfeeding: A Consensus Statement. ACTAS DERMO-SIFILIOGRAFICAS 2021; 112:225-241. [PMID: 33065101 DOI: 10.1016/j.ad.2020.10.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 10/02/2020] [Indexed: 02/01/2023] Open
Abstract
OBJECTIVE To develop evidence- and experience-based recommendations for the management of psoriasis during preconception, pregnancy, postpartum, and breastfeeding. METHODS The nominal group technique and the Delphi method were used. Fifteen experts (12 dermatologists, 2 of whom were appointed coordinators; 1 rheumatologist; and 2 gynecologists) were selected to form an expert panel. Following a systematic review of the literature on fertility, pregnancy, postpartum, and breastfeeding in women with psoriasis, the coordinators drew up a series of preliminary recommendations for discussion by the panel at a nominal group meeting. The experts defined the scope, sections, and intended users of the statement and prepared a final list of recommendations. Consensus was obtained using a Delphi process in which an additional 51 dermatologists rated their level of agreement with each recommendation on a scale of 1 (total disagreement) to 10 (total agreement). Consensus was defined by a score of 7 or higher assigned by at least 70% of participants. Level of evidence and strength of recommendation were reported using the Oxford Center for Evidence-Based Medicine categories. The final statement was approved by the expert panel. RESULTS The resulting consensus statement includes 23 recommendations on preconception (fertility and contraception), pregnancy (planning, pharmacological management, and follow-up), and breastfeeding (management and follow-up). Consensus was achieved for all recommendations generated except one. CONCLUSIONS These recommendations for the better management of psoriasis in women of childbearing age could improve outcomes and prognosis.
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Affiliation(s)
- I Belinchón
- Servicio de Dermatología, Hospital General Universitario de Alicante-ISABIAL-UMH, Alicante, España.
| | - M Velasco
- Servicio de Dermatología, Hospital Universitario Arnau de Vilanova, Valencia, España
| | - M Ara-Martín
- Servicio de Dermatología, Hospital Clínico Lozano Blesa, Zaragoza, España
| | - S Armesto Alonso
- Servicio de Dermatología, Hospital Universitario Marqués de Valdecilla, Santander, España
| | | | - L Ferrándiz Pulido
- Servicio de Dermatología, Hospital Universitario Virgen Macarena, Sevilla, España
| | - M García-Bustinduy
- Servicio de Dermatología, Hospital Universitario de Canarias, Santa Cruz de Tenerife, España
| | - J A Martínez-López
- Servicio de Reumatología, Hospital Universitario Fundación Jiménez Díaz, Madrid, España
| | - N Martínez Sánchez
- Servicio de Ginecología-Obstetricia, Hospital Universitario La Paz, Madrid, España
| | - A Pérez Ferriols
- Servicio de Dermatología, Hospital General de Valencia, Valencia, España
| | - E Pérez Pascual
- Servicio de Ginecología-Obstetricia, Hospital General Universitario de Alicante-ISABIAL, Alicante, España
| | - R Rivera Díaz
- Servicio de Dermatología, Hospital Universitario 12 de Octubre, Madrid, España
| | - R Ruiz-Villaverde
- Servicio de Dermatología, Hospital Universitario San Cecilio, Granada, España
| | - R Taberner Ferrer
- Servicio de Dermatología, Hospital Son Llàtzer, Palma de Mallorca, España
| | - A Vicente Villa
- Servicio de Dermatología, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, España
| | - J M Carrascosa
- Servicio de Dermatología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, España
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14
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Belinchón I, Velasco M, Ara-Martín M, Armesto Alonso S, Baniandrés Rodríguez O, Ferrándiz Pulido L, García-Bustinduy M, Martínez-López J, Martínez Sánchez N, Pérez Ferriols A, Pérez Pascual E, Rivera Díaz R, Ruiz-Villaverde R, Taberner Ferrer R, Vicente Villa A, Carrascosa J. Management of Psoriasis During Preconception, Pregnancy, Postpartum, and Breastfeeding: A Consensus Statement. ACTAS DERMO-SIFILIOGRAFICAS 2021. [DOI: 10.1016/j.adengl.2020.10.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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15
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De Lorenzo R, Ramirez GA, Punzo D, Lorioli L, Rovelli R, Canti V, Barera G, Rovere-Querini P. Neonatal outcomes of children born to mothers on biological agents during pregnancy: State of the art and perspectives. Pharmacol Res 2019; 152:104583. [PMID: 31816434 DOI: 10.1016/j.phrs.2019.104583] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 11/29/2019] [Accepted: 11/30/2019] [Indexed: 12/19/2022]
Abstract
Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are used in pregnant patients with rheumatic diseases. Long-term follow-up data about newborns exposed to bDMARDs during pregnancy are however scarce. Here we summarize the published evidence and available recommendations for use of bDMARDs during pregnancy. We analyse clinical features at birth and at follow-up of 84 children, including: 16 consecutive children born to mothers with autoimmune diseases exposed to bDMARDs in utero; 32 children born to mothers with autoimmune diseases who did not receive bDMARDs; 36 children born to healthy mothers. In our monocentric cohort, children born to mothers with autoimmune diseases had lower gestational age at birth compared to those born to healthy mothers, independently of exposure to bDMARDs. At multivariate analysis, prematurity was an independent predictor of the need for antibiotic treatment, but not for hospitalisation or neonatal intensive care unit (ICU) stay during the neonatal period. Exposure to bDMARDs during pregnancy does not seem to interfere with post-natal development up to infancy. Prospective studies are needed in larger cohorts of pregnant patients to confirm that bDMARDs do not have a negative impact on psychomotor achievements in newborns.
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Affiliation(s)
- Rebecca De Lorenzo
- Università Vita-Salute San Raffaele, Milan, Italy; Department of Medicine and Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Giuseppe A Ramirez
- Università Vita-Salute San Raffaele, Milan, Italy; Department of Medicine and Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Daniele Punzo
- Università Vita-Salute San Raffaele, Milan, Italy; Department of Medicine and Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Laura Lorioli
- Unit of Paediatrics, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Rosanna Rovelli
- Unit of Paediatrics, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valentina Canti
- Università Vita-Salute San Raffaele, Milan, Italy; Department of Medicine and Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Graziano Barera
- Unit of Paediatrics, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Patrizia Rovere-Querini
- Università Vita-Salute San Raffaele, Milan, Italy; Department of Medicine and Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
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16
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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]
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17
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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: 173] [Impact Index Per Article: 24.7] [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.
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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
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18
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Brown SM, Aljefri K, Waas R, Hampton P. Systemic medications used in treatment of common dermatological conditions: safety profile with respect to pregnancy, breast feeding and content in seminal fluid. J DERMATOL TREAT 2018; 30:2-18. [PMID: 28092212 DOI: 10.1080/09546634.2016.1202402] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Prescribing for pregnant or lactating patients and male patients wishing to father children can be a difficult area for dermatologists. There is a lack of review articles of commonly used systemic medications in dermatology with respect to their effects on developing embryogenesis and their potential transfer across the placenta, in breast milk and in seminal fluid. This paper aims to provide an up to date summary of evidence to better equip dermatologists to inform patients about the effects of systemic medications commonly used in dermatology to treat conditions such as atopic dermatitis, psoriasis and acne, on current and future embryogenesis and fertility.
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Affiliation(s)
| | - Khadija Aljefri
- a Dermatology Department , Royal Victoria Infirmary , Newcastle Upon Tyne , UK
| | - Rachel Waas
- a Dermatology Department , Royal Victoria Infirmary , Newcastle Upon Tyne , UK
| | - Philip Hampton
- a Dermatology Department , Royal Victoria Infirmary , Newcastle Upon Tyne , UK
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19
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Önalan G, Tohma YA, Zeyneloğlu HB. Effect of Etanercept on the Success of Assisted Reproductive Technology in Patients with Endometrioma. Gynecol Obstet Invest 2017; 83:358-364. [PMID: 29208847 DOI: 10.1159/000484895] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 10/31/2017] [Indexed: 12/20/2022]
Abstract
AIMS To determine the effects of a tumor necrosis factor inhibitor (etanercept) on pregnancy outcomes in patients with endometrioma who were treated with assisted reproductive technology. METHODS Sixty-eight infertile patients who had endometrioma were included in our retrospective case-control study. We administered etanercept (Enbrel, 50 mg in 1 mL intramuscularly) to 19 patients on the second day of their previous menstrual cycle. All patients were treated with assisted reproductive technology. Pregnancy and live birth rates (LBR) were documented. RESULTS When all other parameters (age, body mass index, infertility) are supposed to be constant, the clinical pregnancy rate was significantly higher in patients who used etanercept in an antagonist protocol than in patients who did not use etanercept (χ2 = 5.547; p = 0.019) but LBR did not reach a statistical significance (χ2 = 3.179; p = 0.075). The use of etanercept had an OR of 4.17 (95% CI 1.23-14.14) compared with not using etanercept for clinical pregnancy rate. The use of etanercept increased the rate of pregnancy (χ2 = 6.55; p = 0.01). The pregnancy rate with the use of etanercept had an OR of 4.23 (95% CI 1.35-13.25) compared with patients who did not use etanercept. In the same way, the use of etanercept increased LBR twofold, but it is not significant in the border line (χ2 = 3.771; p = 0.052). CONCLUSIONS Etanercept may be a new non-hormonal therapy that may be an adjunct to treatment of infertile women with endometrioma. However, the safety of etanercept on embryos and fetuses has not been fully clarified.
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20
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Detrimental roles of TNF-alpha in the antiphospholipid syndrome and de novo synthesis of antiphospholipid antibodies induced by biopharmaceuticals against TNF-alpha. J Thromb Thrombolysis 2017; 44:565-570. [DOI: 10.1007/s11239-017-1571-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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21
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Hoxha A, Calligaro A, Di Poi E, Peccatori S, Favaro M, Del Ross T, Ramonda R, Grava C, Raffeiner B, Ravagni P, De Vita S, Ruffatti A. Pregnancy and foetal outcomes following anti-tumor necrosis factor alpha therapy: A prospective multicentre study. Joint Bone Spine 2017; 84:169-173. [DOI: 10.1016/j.jbspin.2016.03.014] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 03/24/2016] [Indexed: 02/07/2023]
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22
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Abrouk M, Beroukhim K, Nakamura M, Zhu TH, Farahnik B, Singh R, Lee K, Koo J, Bhutani T. Considerations on biologic agents in psoriasis with the new pregnancy lactation labeling rule. Int J Womens Dermatol 2017; 3:S67-S69. [PMID: 28492043 PMCID: PMC5419054 DOI: 10.1016/j.ijwd.2017.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 02/02/2016] [Accepted: 02/02/2016] [Indexed: 11/06/2022] Open
Affiliation(s)
- Michael Abrouk
- Irvine School of Medicine, University of California, Irvine, CA
| | - Keroush Beroukhim
- David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA
| | - Mio Nakamura
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
| | - Tian Hao Zhu
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | | | - Rasnik Singh
- David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA
| | - Kristina Lee
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
| | - John Koo
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
| | - Tina Bhutani
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
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23
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Burmester GR, Landewé R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis 2017; 76:414-417. [PMID: 27338778 PMCID: PMC5284339 DOI: 10.1136/annrheumdis-2016-209322] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 04/25/2016] [Accepted: 05/27/2016] [Indexed: 12/27/2022]
Abstract
BACKGROUND Adalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications. OBJECTIVE To update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA. METHODS This analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials. AEs of interest included overall infections, laboratory abnormalities and AEs associated with influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry. RESULTS Serious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. Two patients experienced hepatitis B reactivation. No significant laboratory abnormalities were reported with adalimumab-plus-methotrexate compared with placebo-plus-methotrexate. Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study. Relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women were similar between that of unexposed women with RA and healthy women. CONCLUSIONS This analysis confirms and expands the known safety profile of adalimumab and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defects. The benefits of influenza vaccination are reinforced. TRIAL REGISTRATION NUMBERS NCT00195663, NCT00195702, NCT00448383, NCT00049751, NCT00234845, NCT00650390, NCT00235859, NCT00647920, NCT00649545, NCT00647491, NCT00649922, NCT00538902, NCT00420927, NCT00870467, NCT00650156, NCT00647270, NCT01185288, NCT01185301.
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Affiliation(s)
- Gerd R Burmester
- Department of Rheumatology and Clinical Immunology, Charité–University Medicine Berlin, Free University and Humboldt University of Berlin, Berlin, Germany
| | - Robert Landewé
- Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Mark C Genovese
- Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA
| | - Alan W Friedman
- Immunology Clinical Development, AbbVie, North Chicago, Illinois, USA
| | - Nathan D Pfeifer
- Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA
| | - Nupun A Varothai
- Data and Statistical Sciences, AbbVie, North Chicago, Illinois, USA
| | - Ana P Lacerda
- Immunology Clinical Development, AbbVie, North Chicago, Illinois, USA
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24
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Lund T, Thomsen SF. Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy: A patient series. Dermatol Ther 2017; 30. [PMID: 28071837 DOI: 10.1111/dth.12454] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 10/25/2016] [Accepted: 10/31/2016] [Indexed: 02/06/2023]
Abstract
From 2002 to 2016 a total of seven women with severe refractory psoriasis were exposed to the TNF-inhibitors infliximab and adalimumab or to the IL12/23 inhibitor ustekinumab during one or more pregnancies. Maternal, fetal or teratogenic toxicity were not detected during pregnancy and puerperium. All pregnancies were uneventful and resulted in delivery of 10 healthy children in total, one of the women is due February 2017. Postpartum, five of the women were lactating, but none of the women or newborns developed adverse reactions. Data on safety of treatment during breastfeeding are sparse, but so far appears to be safe due to the lack of absorption across the gastrointestinal lining. Currently biological therapy with either TNF-inhibitors or ustekinumab is not recommended during pregnancy, however in selected women with severe psoriasis these treatment modalities may be considered.
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Affiliation(s)
- Tamara Lund
- Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark
| | - Simon Francis Thomsen
- Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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25
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Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and Comprehensive Review. Clin Rev Allergy Immunol 2017; 53:40-53. [DOI: 10.1007/s12016-016-8596-x] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Abdolmohammadi-Vahid S, Danaii S, Hamdi K, Jadidi-Niaragh F, Ahmadi M, Yousefi M. Novel immunotherapeutic approaches for treatment of infertility. Biomed Pharmacother 2016; 84:1449-1459. [DOI: 10.1016/j.biopha.2016.10.062] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 10/18/2016] [Accepted: 10/21/2016] [Indexed: 10/20/2022] Open
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Flynn A, Burke N, Byrne B, Gleeson N, Wynne B, Barnes L. Two case reports of generalized pustular psoriasis of pregnancy: Different outcomes. Obstet Med 2016; 9:55-9. [PMID: 27512494 PMCID: PMC4950411 DOI: 10.1177/1753495x15626623] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Accepted: 12/02/2015] [Indexed: 12/18/2022] Open
Abstract
Generalized pustular psoriasis of pregnancy is a rare dermatosis with potential serious consequences for both the mother and fetus. Treatment is difficult and historically steroids were the mainstay of treatment. Cyclosporin has been used for a few cases resistant to steroids. We report our own experience of two cases of generalized pustular psoriasis of pregnancy. Cases of generalized pustular psoriasis of pregnancy need review by a dermatologist with experience of skin disorders in pregnancy. Both the fetus and mother need to be monitored closely when systemic illness occurs, as there is a risk of stillbirth. Maternal sepsis is a known complication of generalized pustular psoriasis of pregnancy. Cyclosporin, when used appropriately is effective and relatively safe.
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Affiliation(s)
- Aoibheann Flynn
- Department of Dermatology, St. James’s Hospital Dublin, Dublin, Ireland
| | - Naomi Burke
- Department of Gynaecology, St. James’s Hospital Dublin, Dublin, Ireland
| | - Bridgette Byrne
- Department of Obstetrics and Gynaecology, The Coombe Women and Infants Maternity Hospital, Dublin, Ireland
| | - Noreen Gleeson
- Department of Gynaecology, St. James’s Hospital Dublin, Dublin, Ireland
| | - Bairbre Wynne
- Department of Dermatology, St. James’s Hospital Dublin, Dublin, Ireland
| | - Louise Barnes
- Department of Dermatology, St. James’s Hospital Dublin, Dublin, Ireland
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Wan J, Imadojemu S, Werth VP. Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum. Clin Dermatol 2016; 34:344-52. [DOI: 10.1016/j.clindermatol.2016.02.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Abrouk M, Beroukhim K, Nakamura M, Zhu TH, Farahnik B, Singh R, Brodsky M, Lee K, Koo J, Bhutani T. Considerations on biologic agents in psoriasis with the new pregnancy lactation labeling rule. Int J Womens Dermatol 2016; 2:62-64. [PMID: 28492009 PMCID: PMC5412117 DOI: 10.1016/j.ijwd.2016.02.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 02/02/2016] [Accepted: 02/02/2016] [Indexed: 11/05/2022] Open
Affiliation(s)
- Michael Abrouk
- Irvine School of Medicine, University of California, Irvine, CA
| | - Kourosh Beroukhim
- David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA
| | - Mio Nakamura
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
| | - Tian Hao Zhu
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | | | - Rasnik Singh
- David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA
| | - Merrick Brodsky
- Irvine School of Medicine, University of California, Irvine, CA
| | - Kristina Lee
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
| | - John Koo
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
| | - Tina Bhutani
- Department of Dermatology, Psoriasis, and Skin Treatment Center, University of California, San Francisco, CA
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Bangsgaard N, Rørbye C, Skov L. Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments. Am J Clin Dermatol 2015; 16:389-98. [PMID: 26149091 DOI: 10.1007/s40257-015-0137-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment.
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Affiliation(s)
- Nannie Bangsgaard
- Herlev and Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, 2900, Hellerup, Denmark.
| | - Christina Rørbye
- Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, 2650, Hvidovre, Denmark
| | - Lone Skov
- Herlev and Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, 2900, Hellerup, Denmark
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Garip Y. Use of biologic agents for rheumatic diseases in pregnancy. World J Rheumatol 2015; 5:50-58. [DOI: 10.5499/wjr.v5.i2.50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 03/03/2015] [Accepted: 05/06/2015] [Indexed: 02/06/2023] Open
Abstract
Biologic agents have ushered a new era in the treatment of inflammatory rheumatic diseases. In recent years, several biologic agents have been approved by food and drug administration and have significantly improved outcomes for patients with immune mediated inflammatory disorders including rheumatic and inflammatory bowel diseases. The most common used biologic therapeutic agents are tumor necrosis factor inhibitors (etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab), an interleukin (IL)-6 inhibitor (tocilizumab), an IL-1 receptor antagonist (anakinra), an anti-CD-20 antibody (rituximab), and a T cell co-stimulation modulator (abatacept). Their use during pregnancy has been controversial because of absence of controlled studies which have enrolled pregnant women. This brief overview provides published data on use of biologic agents for the treatment of rheumatic diseases in pregnancy.
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Mena-Vazquez N, Manrique-Arija S, Fernandez-Nebro A. Safety of biologic therapies during pregnancy in women with rheumatic disease. World J Rheumatol 2015; 5:82-89. [DOI: 10.5499/wjr.v5.i2.82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 09/08/2014] [Accepted: 04/07/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory rheumatic diseases frequently affect women of childbearing age. Biologic therapy during pregnancy is an important topic that is yet unresolved. The majority of documented experiences are in case series, case reports, or registries. Tumor necrosis factor (TNF) inhibitors are now better known. Some evidence suggests that it is possible that differences between drugs regarding safety are associated with the structure and capacity to cross the placenta, but we are not aware of any study that supports unequivocally this statement. Most of the monoclonal antibodies are actively transferred to fetal circulation using the neonatal Fc receptor. Although this transfer does not appear to be associated with the risk of miscarriage, stillbirth, or congenital abnormality, the rate of premature births and lower birth weight may be increased. During fetal development, the neonatal period, and childhood, the immune system is constantly maturing. The ability to produce cytokines in response to infectious stimulus remains low for years, but is similar to that of an adult around the age of 3 years owing to the adaptive nature of the newborn’s immune system as a result of exposure to microbes. Therefore, exposure to TNF inhibitors may have serious consequences on the newborn, such as severe infections or allergic reactions. Regarding the former, an anecdotal case report described a fatal case of disseminated bacillus Calmette-Guérin (BCG) infection in an infant born to a mother taking infliximab for Crohn’s disease. Although the baby was born and progressed well initially, he died at 4.5 mo after he was vaccinated with BCG. Fortunately, serious infections do not appear to be frequent in newborns exposed to in utero biologic therapy. However, very limited short-term experiences are available regarding complications in an exposed fetus, and no data are available about long-term implications on the child’s developing immune system. Therefore, we must be aware of potential complications in later years. Although the clinical data to date are promising, no firm conclusions can be drawn about the safety of biologic drugs during pregnancy, and, without further evidence, guidelines that suggest these drugs should be avoided at the time of conception cannot yet be changed.
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Khan N, Asim H, Lichtenstein GR. Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy. Expert Opin Drug Saf 2015; 13:1699-708. [PMID: 25406728 DOI: 10.1517/14740338.2014.973399] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The highest incidence of inflammatory bowel disease (IBD) is seen between the second and fourth decades of life, which is the most fertile age for women. Increased disease activity has been shown to effect female fertility and pregnancy outcomes, stressing the need for drugs that can safely induce and maintain clinical remission without harming either the mother or fetus. AREAS COVERED Anti-TNF-α agents have been shown to be effective in both inducing and maintaining remission among IBD patients. This review highlights the results of previous studies conducted on pregnant women who were exposed to anti-TNF-α agents during the course of their pregnancy. The drugs reviewed include infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP) and golimumab (GMB). Of > 200 articles reviewed, 105 were included in the manuscript based on relevance. The keywords used were anti-TNF, infliximab, adalimumab, certolizumab, golimumab, biologics, pregnancy and inflammatory bowel disease. EXPERT OPINION Anti-TNF agents have been studied extensively during pregnancy from the early case reports to the more recent prospective Pregnancy in IBD and Neonatal Outcomes study. A comprehensive review of the literature has shown that biologics can be safely used during pregnancy. In view of this safety data, it is recommended to maintain therapy during pregnancy.
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Affiliation(s)
- Nabeel Khan
- University of Pennsylvania Perelman School of Medicine, Department of Gastroenterology , Philadelphia, PA , USA
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Hoffman MB, Farhangian M, Feldman SR. Psoriasis during pregnancy: characteristics and important management recommendations. Expert Rev Clin Immunol 2015; 11:709-20. [DOI: 10.1586/1744666x.2015.1037742] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Potential neuroprotective strategies for perinatal infection and inflammation. Int J Dev Neurosci 2015; 45:44-54. [DOI: 10.1016/j.ijdevneu.2015.02.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 02/16/2015] [Accepted: 02/16/2015] [Indexed: 01/17/2023] Open
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Ruiz V, Manubens E, Puig L. Psoriasis In Pregnancy: A Review (II). ACTAS DERMO-SIFILIOGRAFICAS 2014. [DOI: 10.1016/j.adengl.2014.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Khan N, Asim H, Lichtenstein GR. Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy. Expert Opin Drug Saf 2014. [DOI: 10.1517/14740338.2015.973399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Krause ML, Amin S, Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis 2014; 6:169-84. [PMID: 25342996 DOI: 10.1177/1759720x14551568] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease of synovial joints, can lead to chronic pain and structural joint damage, as well as other organ involvement, especially if not adequately controlled. Because it can affect women in their reproductive years, care of pregnant women with RA requires a delicate balance of maintaining disease control while limiting potential toxicity to the fetus and neonate. While most women experience a substantial improvement in disease activity during pregnancy, for some women their RA remains active. It can even manifest itself for the first time during pregnancy or early in the post-partum period. Optimizing disease control prior to conception is key, but utilizing disease-modifying treatments effectively and safely throughout pregnancy and lactation requires open dialogue and shared decision making. This review provides evidence-based recommendations for use of disease-modifying antirheumatic drugs (DMARDs) and biologic response modifiers to guide rheumatologists in their care of pregnant and lactating women with RA and serves as a guide to counsel male patients with RA on family planning decisions.
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Affiliation(s)
- Megan L Krause
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Shreyasee Amin
- Division of Rheumatology, Department of Internal Medicine; and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Ashima Makol
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
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Management of the pregnant inflammatory bowel disease patient on anti-tumour necrosis factor: state of the art and future directions. Can J Gastroenterol Hepatol 2014; 28:505-9. [PMID: 25101334 PMCID: PMC4205908 DOI: 10.1155/2014/967598] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Antitumour necrosis factor (anti-TNF) therapy has been a major advance in the treatment of inflammatory bowel disease (IBD) by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta), recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.
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Guiddir T, Frémond ML, Triki TB, Candon S, Croisille L, Leblanc T, de Pontual L. Anti-TNF-α therapy may cause neonatal neutropenia. Pediatrics 2014; 134:e1189-93. [PMID: 25266439 DOI: 10.1542/peds.2014-0054] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Although anti-tumor necrosis factor (anti-TNF) antibodies are associated with a clear risk of agranulocytosis in adults and are known to cross the placenta, monitoring of the absolute neutrophil count (ANC) in neonates born to mothers receiving these biological agents is not currently recommended. Here, we report on the first case series of 4 newborn patients with severe neutropenia born to mothers treated for ulcerative colitis with infliximab during pregnancy (including the third trimester). The newborns presented with severe neutropenia at birth, which was subsequently complicated by skin infections. The newborns' ANCs returned to the normal range within 8 to 14 weeks, at which time infliximab could not be detected in the blood. Anti-TNF agents probably exert a direct, toxic effect on the bone marrow. Furthermore, the detection of a CD16 autoantibody in 1 mother-newborn pair suggests that infliximab can induce autoimmune neutropenia. Abnormally high levels of the CD16 autoantibody in newborn serum or immaturity of the fetal bone marrow might explain why neutropenia was observed in the child but not in the mother. We recommend the systematic measurement of ANC on cord blood at birth and (in the event of an infection) in the weeks thereafter.
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Affiliation(s)
| | | | - Tewfik Bibi Triki
- Laboratoire d'Hématologie, Université Paris 13, Sorbonne Paris Cité, Hôpital Jean Verdier, Assistance Publique des Hôpitaux de Paris, Bondy Cedex, France
| | - Sophie Candon
- Laboratoire d'Immunologie, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, Paris, France
| | | | - Thierry Leblanc
- Service d'Hématologie Pédiatrique, Hôpital Robert Debré, AP-HP, Paris, France
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Ergaz Z, Bar-Oz B, Vainer GW, Abu-Leil S, Simanovsky N, Diav-Citrin O. Congenital fulminant Kaposiform hemangioendothelioma of the leg. Reprod Toxicol 2014; 50:1-3. [PMID: 25277314 DOI: 10.1016/j.reprotox.2014.09.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Revised: 09/16/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023]
Abstract
Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor associated with Kasabach Merritt syndrome. We present a case of congenital Kaposiform hemangioendothelioma of the leg in a female infant who was born to a mother treated with various medications including etanercept, a TNF antagonist, due to rheumatoid arthritis. The neonate suffered from a fulminant form of Kasabach Merritt syndrome with disseminated intravascular coagulation (DIC) resulting in multi-organ failure which led to her demise.
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Affiliation(s)
- Zivanit Ergaz
- Department of Neonatology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
| | - Benjamin Bar-Oz
- Department of Neonatology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Gilad W Vainer
- Department of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Sinan Abu-Leil
- Department of Neonatology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Natalia Simanovsky
- Department of Medical Imaging, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Orna Diav-Citrin
- The Israeli Teratology Information Service, Israel Ministry of Health, Jerusalem, Israel
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43
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Matz H. Biologics in the Treatment of Skin Diseases During Pregnancy and Lactation. CURRENT DERMATOLOGY REPORTS 2014. [DOI: 10.1007/s13671-014-0085-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Yiu ZZN, Griffiths CEM, Warren RB. Safety of biological therapies for psoriasis: effects on reproductive potential and outcomes in male and female patients. Br J Dermatol 2014; 171:485-91. [PMID: 24749725 DOI: 10.1111/bjd.13060] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2014] [Indexed: 02/06/2023]
Abstract
The effects of biological therapies for psoriasis on pregnancy outcomes and lactation, and male fertility and mutagenicity are common concerns in the clinical setting. There is relatively little evidence to guide the clinician and patient. Here, we review the safety profile of the commonly used biological therapies for psoriasis in individuals of reproductive potential. Safety data were derived from large-scale registries, adverse event reporting databases, clinical trials and case reports. We assessed the effect of each therapy on adverse pregnancy outcomes including congenital malformations, and lactation with maternal administration, and male fertility and potential mutagenicity with paternal administration. We provide applicable guidance to inform clinician and patient before and after conception.
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Affiliation(s)
- Z Z N Yiu
- The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, M6 8HD, U.K
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45
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Seifarth C, Ritz JP, Pohlen U, Kroesen AJ, Siegmund B, Frericks B, Buhr HJ. Therapy of complicated Crohn's disease during pregnancy--an interdisciplinary challenge. Int J Colorectal Dis 2014; 29:645-51. [PMID: 24793212 DOI: 10.1007/s00384-014-1880-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/18/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Severe courses of Crohn's disease (CD) during pregnancy are rare. However, if occurring, the risk of miscarriage and low birth weight is increased. At present, only limited data is available on the treatment of CD during pregnancy. In particular, there are no standard guidelines for surgical therapy. Nevertheless, surgery is often unavoidable if complications during the course of the disease arise. PURPOSE This study provides a critical overview of conventional and interventional treatment options for CD complications during pregnancy and analyses the surgical experience gained thus far. For illustrative purposes, clinical cases of three young women with a severe clinical course during pregnancy are presented. METHODS After treatment-refractory for conservative and interventional measures, surgery remained as the only treatment option. In all cases, a split stoma was created after resection to avoid anastomotic leaks that would endanger the lives of mother and child. The postoperative course of all three patients was uneventful, and pregnancy remained intact until delivery. No further CD specific medication was required before birth. CONCLUSIONS The management of CD patients during pregnancy requires close interdisciplinary co-operation between gastroenterologists, obstetricians, anaesthetists and visceral surgeons. For the protection of mother and child treatment should thus be delivered in a specialised centre. This article demonstrates the advantages of surgical therapy by focusing on alleviating CD complaints and preventing postoperative complications.
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Affiliation(s)
- C Seifarth
- Department of General, Visceral and Vascular Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany,
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Ostensen M. Safety issues of biologics in pregnant patients with rheumatic diseases. Ann N Y Acad Sci 2014; 1317:32-8. [PMID: 24840548 DOI: 10.1111/nyas.12456] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The safety of biologic agents during pregnancy is still being investigated. Tumor necrosis factor α (TNF-α) inhibitors are the only well-studied biological drugs in pregnancy; they do not appear to be teratogenic but increase the risk of infection after birth when given in late pregnancy. The long-term effects in exposed children are, at present, unknown. An increased risk of infection is a concern for all biologics and the risk increases further should combination with glucocorticoids be necessary. Experiences with rituximab, abatacept, anakinra, tocilizumab, and belimumab in pregnancy are limited. These drugs should be avoided during pregnancy or used only when no other option is available for treatment of serious maternal disease.
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Affiliation(s)
- Monika Ostensen
- National Service for Pregnancy and Rheumatic Diseases, Department of Rheumatology, Trondheim University Hospital, Trondheim, Norway
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47
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Diav-Citrin O, Otcheretianski-Volodarsky A, Shechtman S, Ornoy A. Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a prospective, comparative, observational study. Reprod Toxicol 2014; 43:78-84. [PMID: 24284028 DOI: 10.1016/j.reprotox.2013.11.004] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Revised: 10/29/2013] [Accepted: 11/14/2013] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To evaluate pregnancy safety of anti-TNF-α medications. DESIGN Prospective, comparative, observational study done at the Israeli Teratology Information Service between 2002 and 2011. RESULTS 83 anti-TNF-α-exposed-pregnancies (97.6% in the first trimester, T1) were followed-up and compared with 86 disease-matched (DM) and 341 non-teratogenic-exposed (NTE) pregnancies. The anti-TNF-α group consisted of 35 infliximab-, 25 etanercept-, and 23 adalimumab-exposed pregnancies. The rate of major congenital anomalies did not significantly differ between the three groups [3/65 (4.6%) (anti-TNF-α, T1), 5/79 (6.3%) (DM), 8/336 (2.4%) (NTE)], even after excluding genetic or cytogenetic anomalies [3/65 (4.6%) (anti-TNF-α, T1), 4/79 (5.1%) (DM), 6/336 (1.8%) (NTE)]. There were no cases of VATER/VACTERL association. CONCLUSION The present study suggests that anti-TNF-α treatment does not pose a major teratogenic risk in humans. This conclusion is based on relatively small numbers of exposed pregnancies and should be interpreted with caution. Larger studies are needed to establish anti-TNF-α pregnancy safety.
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Affiliation(s)
- Orna Diav-Citrin
- The Israeli Teratology Information Service, Israel Ministry of Health, Jerusalem, Israel; The Hebrew University Hadassah Medical School, Jerusalem, Israel.
| | | | - Svetlana Shechtman
- The Israeli Teratology Information Service, Israel Ministry of Health, Jerusalem, Israel
| | - Asher Ornoy
- The Israeli Teratology Information Service, Israel Ministry of Health, Jerusalem, Israel; The Hebrew University Hadassah Medical School, Jerusalem, Israel
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Ruiz V, Manubens E, Puig L. Psoriasis in pregnancy: a review (II). ACTAS DERMO-SIFILIOGRAFICAS 2013; 105:813-21. [PMID: 24314892 DOI: 10.1016/j.ad.2013.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 06/10/2013] [Accepted: 06/17/2013] [Indexed: 12/16/2022] Open
Abstract
Scarce scientific evidence is available to define the precise effects that certain drugs might have on embryonic and fetal development if taken by pregnant women with psoriasis, given the ethical concerns that preclude enrolling such women in clinical trials. The little information on the use of biologics during gestation that has been published is based on retrospective and observational studies, and experience with these drugs in this context in psoriasis is still very limited. The literature seems to suggest that biologic therapy is safe during pregnancy, but there is no certainty. This detailed review of accumulated experience with biologic therapy during pregnancy relies mainly on descriptions of the management of other types of rheumatic disease, although the use of these agents in psoriasis is growing steadily.
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Affiliation(s)
- V Ruiz
- Servicio de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España.
| | - E Manubens
- Servicio de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - L Puig
- Servicio de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
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Abstract
INTRODUCTION Biological therapies have revolutionized moderate-to-severe psoriasis treatment. Increased understanding of disease pathogenesis has yielded multiple therapeutic targets involving the IL-23/Th17 pathway, while current therapies continue to be monitored for long-term efficacy and safety. AREAS COVERED This review details current understanding of psoriasis immunopathogenesis specifically related to therapeutic targets. Approved and emerging biological psoriasis therapies targeting TNF-α, IL-12/23p40, IL-17 and IL-23p19 are covered. Biological agent uses in special circumstances are reviewed together with the emerging debate on biosimilar therapies and their potential future role in psoriasis and other inflammatory diseases. EXPERT OPINION Psoriasis treatment has expanded and has become more effective due to increased understanding of disease pathogenesis. However, lack of efficacy in select psoriasis patients, safety concerns and limited treatment efficacy in psoriasis variants (e.g., pustular) are areas which still need improvement. As such, pharmacogenomics will be of vital importance in future for individualized psoriasis care. Further, a better understanding of the multiple psoriasis comorbidities, especially cardiovascular disease, continues to be of significant interest in the psoriasis community. Last, the emergence of biosimilar agents has the potential to change psoriasis treatment, especially as it relates to better access for the psoriasis community worldwide.
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Affiliation(s)
- Bobbak Mansouri
- Dermatology Research FellowBaylor University Medical Center, Division of Dermatology , 3900 Junius Street, Suite 125, Dallas, TX 75204 , USA
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Abstract
Anticytokine therapies have revolutionized the treatment of chronic inflammatory diseases, particularly autoimmune diseases such as rheumatoid arthritis. As the first introduced principle of cytokine blockade in the 1990s, tumor necrosis factor (TNF)-α antagonists still represent the leading anticytokine therapy. There are currently five TNF antagonists available with indications in the fields of rheumatology, dermatology, and gastroenterology. Other therapeutic approaches have been introduced in the last 10 years, e.g., the blockade of interleukin (IL)-1, IL-6, and IL-12/23. The advantages of cytokine blockers are their rapid onset of action with high response rates and a tolerable safety profile. Nevertheless, anticytokine therapy can cause increased rates of tuberculosis and hepatitis B infections or reactivation. An appropriate screening before therapy is mandatory, and thorough monitoring of the disease course before and during therapy is also important. The development of further anticytokine drugs for the induction and maintenance of remission is, therefore, required.
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Affiliation(s)
- L Naumann
- Medizinische Klinik mit Schwerpunkt für Rheumatologie und klinische Immunologie, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin
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