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      Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

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          Abstract

          Background

          Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified.

          Objective

          Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy.

          Material and Methods

          A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications.

          Results

          A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population.

          Conclusion

          Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations.

          Electronic supplementary material

          The online version of this article (10.1007/s40265-020-01376-y) contains supplementary material, which is available to authorized users.

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          Most cited references159

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          GRADE guidelines: 3. Rating the quality of evidence.

          This article introduces the approach of GRADE to rating quality of evidence. GRADE specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies. In the context of a systematic review, quality reflects our confidence that the estimates of the effect are correct. In the context of recommendations, quality reflects our confidence that the effect estimates are adequate to support a particular recommendation. Randomized trials begin as high-quality evidence, observational studies as low quality. "Quality" as used in GRADE means more than risk of bias and so may also be compromised by imprecision, inconsistency, indirectness of study results, and publication bias. In addition, several factors can increase our confidence in an estimate of effect. GRADE provides a systematic approach for considering and reporting each of these factors. GRADE separates the process of assessing quality of evidence from the process of making recommendations. Judgments about the strength of a recommendation depend on more than just the quality of evidence. Copyright © 2011 Elsevier Inc. All rights reserved.
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            The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.

            A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease.
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              Understanding GRADE: an introduction.

              Grading of recommendations, assessment, development, and evaluations (GRADE) is arguably the most widely used method for appraising studies to be included in systematic reviews and guidelines. In order to use the GRADE system or know how to interpret it when reading reviews, reading several articles and attending a workshop are required. Moreover, the GRADE system is not covered in standard medical textbooks. Here, we explain GRADE concisely with the use of examples so that students and other researchers can understand it. In order to use or interpret the GRADE system, reading several articles and attending a workshop is currently required. Moreover, the GRADE system is not covered in standard medical textbooks. We read, synthesized, and digested the GRADE publications and contacted GRADE contributors for explanations where required. We composed a digested version of the system in a concise way a general medical audience could understand. We were able to explain the GRADE basics clearly and completely in under 1500 words. While advanced critical appraisal requires judgment, training, and practice, it is possible for a non-specialist to grasp GRADE basics very quickly. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.
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                Author and article information

                Contributors
                n.ghalandari@erasmusmc.nl
                Journal
                Drugs
                Drugs
                Drugs
                Springer International Publishing (Cham )
                0012-6667
                1179-1950
                27 August 2020
                27 August 2020
                2020
                : 80
                : 16
                : 1699-1722
                Affiliations
                [1 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Rheumatology, , Erasmus University Medical Center, ; Rotterdam, The Netherlands
                [2 ]GRID grid.491235.8, ISNI 0000 0004 0465 5952, Medicines Evaluation Board (MEB), ; Graadt van Roggenweg 500, 3531 AH Utrecht, The Netherlands
                [3 ]GRID grid.419940.1, ISNI 0000 0004 0631 9549, Netherlands Pharmacovigilance Centre Lareb, ; ‘s Hertogenbosch, The Netherlands
                [4 ]GRID grid.5645.2, ISNI 000000040459992X, Academic Center of Inflammunity, , Erasmus University Medical Center, ; Rotterdam, The Netherlands
                [5 ]GRID grid.5477.1, ISNI 0000000120346234, Utrecht University of Medical Sciences, ; Utrecht, The Netherlands
                Author information
                http://orcid.org/0000-0002-7130-2749
                Article
                1376
                10.1007/s40265-020-01376-y
                7568712
                32852745
                9a48a07f-e146-4ae8-9b7e-c7372459f514
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002998, College ter Beoordeling van Geneesmiddelen;
                Categories
                Systematic Review
                Custom metadata
                © Springer Nature Switzerland AG 2020

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