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      Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis

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          Abstract

          Objectives

          We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA).

          Methods

          Female patients with RA aged 20–50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs.

          Results

          A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs.

          Conclusion

          Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy.

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          Most cited references34

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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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            2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

            To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).
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              Global epidemiology of rheumatoid arthritis

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                Author and article information

                Journal
                RMD Open
                RMD Open
                rmdopen
                rmdopen
                RMD Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2056-5933
                2024
                22 March 2024
                : 10
                : 1
                : e003739
                Affiliations
                [1 ] departmentDepartment of Rheumatology , Ringgold_420263Hanyang University Hospital for Rheumatic Diseases , Seoul, Korea
                [2 ] Ringgold_652616Hanyang University Institute for Rheumatology Research , Seoul, Korea
                [3 ] departmentCollege of Pharmacy , Ringgold_26729Chung-Ang University , Seoul, Korea
                [4 ] departmentDepartment of Obstetrics and Gynecology, College of Medicine , Ringgold_26716Hanyang University , Seoul, Korea
                Author notes
                [Correspondence to ] Dr Yoon-Kyoung Sung; sungyk@ 123456hanyang.ac.kr ; Dr Dae Hyun Yoo; dhyoo@ 123456hanyang.ac.kr
                Author information
                http://orcid.org/0000-0001-9420-2129
                http://orcid.org/0000-0003-4493-8837
                http://orcid.org/0000-0001-6691-8939
                Article
                rmdopen-2023-003739
                10.1136/rmdopen-2023-003739
                10961547
                38519107
                19eca208-6e4a-432f-bfb2-77941d84f3b6
                © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 19 September 2023
                : 11 March 2024
                Funding
                Funded by: Ministry of Health & Welfare, Republic of Korea;
                Award ID: HC19C0052
                Award ID: HI19C0481
                Categories
                Epidemiology
                1506
                Original research
                Custom metadata
                unlocked

                rheumatoid arthritis,epidemiology,risk factors
                rheumatoid arthritis, epidemiology, risk factors

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