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Patterns of immunosuppressive drug use during pregnancy in women with systemic vasculitis: A nationwide population-based cohort study

  • Camille Mettler
    Affiliations
    Département de Médecine Interne, Centre de Référence National pour les maladies auto-immunes systémiques rares, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

    Unité de Recherche Clinique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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  • Nathanael Beeker
    Affiliations
    Unité de Recherche Clinique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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  • Mathis Collier
    Affiliations
    Unité de Recherche Clinique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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  • Véronique Le Guern
    Affiliations
    Département de Médecine Interne, Centre de Référence National pour les maladies auto-immunes systémiques rares, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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  • Benjamin Terrier
    Affiliations
    Département de Médecine Interne, Centre de Référence National pour les maladies auto-immunes systémiques rares, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

    Université Paris Cité, Paris, France
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  • Laurent Chouchana
    Correspondence
    Corresponding author at: 27 Rue du Faubourg Saint-Jacques, 75679, Paris Cedex 14, France.
    Affiliations
    Unité de Recherche Clinique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

    Département de Pharmacologie, Centre Régional de Pharmacovigilance, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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Published:January 24, 2023DOI:https://doi.org/10.1016/j.ejim.2023.01.015

      Highlights

      • About 40% of women with systemic vasculitis were treated by immunosuppressive drugs during pregnancy.
      • The number of patients treated with non-recommended immunosuppressant during pregnancy gradually decreased before pregnancy.
      • Proportion of systemic vasculitis flare did not increase significantly during pregnancy.

      Abstract

      Objective

      Systemic vasculitis (SV) rarely affects women of childbearing age and only small series have been reported to date in pregnant patients. The discovery of an unplanned pregnancy can be an urgent cause for modifying treatments. This study aimed to describe immunosuppressive drugs use before, during and after pregnancy in women with SV.

      Methods

      We conducted a cohort study using the French nationwide claims database. We included all women with SV being pregnant between 2013 and 2018. Exposure of interest was defined as exposure to oral systemic or injectable immunosuppressive drug identified using out-hospital reimbursement data and in-hospital reimbursement for expensive drugs.

      Results

      Of 3,246,454 pregnancies, 649 pregnancies were observed in 606 women with SV. Immunosuppressant and glucocorticoids use decreased before pregnancy and then increased after pregnancy (48.4%, 40.7%, 50.4%, respectively before, during, after). Prevalence of glucocorticoids use was broadly stable during pregnancy from 27.9% to 27.6% and 23.7% in the 1st, 2nd and 3rd trimesters, respectively, with a daily dose of about 5 mg. The number of patients treated with non-recommended immunosuppressant during pregnancy gradually decreased before pregnancy and then increased after delivery, whereas proportion of systemic vasculitis flare, estimated from the glucocorticoids daily dose, did not increase significantly during pregnancy.

      Conclusion

      Immunosuppressants and glucocorticoids use decreased before pregnancy and remained stable throughout, suggesting a vasculitis control during this period. Our findings support the importance of pre-conceptional consultations to review medications, and switch not-recommended and teratogenic medications to drugs considered being safe during pregnancy.

      Keywords

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      References

        • Jennette J.C.
        • Falk R.J.
        • Bacon P.A.
        • Basu N.
        • Cid M.C.
        • Ferrario F.
        • et al.
        2012 revised International Chapel Hill consensus conference nomenclature of vasculitides.
        Arthritis Rheum. 2013; 65: 1-11
        • Ross C.
        • D'Souza R.
        • Pagnoux C
        Pregnancy Outcomes in Systemic Vasculitides.
        Curr Rheumatol Rep. 2020; 22 (26): 63
        • Gatto M.
        • Iaccarino L.
        • Canova M.
        • Zen M.
        • Nalotto L.
        • Ramonda R.
        • et al.
        Pregnancy and vasculitis: a systematic review of the literature.
        Autoimmun Rev. 2012; 11: A447-A459
        • Gloor A.D.
        • Chollet L.
        • Christ L.A.
        • Cullmann J.L.
        • Bonel H.M.
        • Villiger P.M.
        Takayasu arteritis: prevalence and clinical presentation in Switzerland.
        PLoS ONE. 2021; 16e0250025
        • Watts R.A.
        • Robson J.
        Introduction, epidemiology and classification of vasculitis.
        Best Pract Res Clin Rheumatol. 2018; 32: 3-20
        • Comarmond C.
        • Saadoun D.
        • Nizard J.
        • Cacoub P.
        Pregnancy issues in Takayasu arteritis.
        Semin Arthritis Rheum. 2020; 50 (Oct 1): 911-914
        • Barros T.
        • Braga A.
        • Marinho A.
        • Braga J.
        Behçet's disease and pregnancy: a retrospective case-control study.
        Yale J Biol Med. 2021; 94: 585-592
        • Machen L.
        • Clowse M.E.B.
        Vasculitis and Pregnancy.
        Rheum Dis Clin North Am. 2017; 43: 239-247
        • Hellmich B.
        • Agueda A.
        • Monti S.
        • Buttgereit F.
        • Boysson H de
        • Brouwer E.
        • et al.
        2018 Update of the EULAR recommendations for the management of large vessel vasculitis.
        Ann Rheum Dis. 2020; 79 (Jan 1): 19-30
        • Hatemi G.
        • Christensen R.
        • Bang D.
        • Bodaghi B.
        • Celik A.F.
        • Fortune F.
        • et al.
        2018 update of the EULAR recommendations for the management of Behçet's syndrome.
        Ann Rheum Dis. 2018; 77 (Jun 1): 808-818
        • Yates M.
        • Watts R.A.
        • Bajema I.M.
        • Cid M.C.
        • Crestani B.
        • Hauser T.
        • et al.
        EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.
        Ann Rheum Dis. 2016; 75: 1583-1594
        • Pecher A.C.
        • Henes M.
        • Henes J.C.
        Optimal management of ANCA-associated vasculitis before and during pregnancy: current perspectives.
        Arch Gynecol Obstet. 2022; (Sep 14)
        • Sammaritano L.R.
        • Bermas B.L.
        • Chakravarty E.E.
        • Chambers C.
        • Clowse M.E.B.
        • Lockshin M.D.
        • et al.
        2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.
        Arthritis Rheumatol Hoboken NJ. 2020; (Feb 23)
        • Eudy A.M.
        • Siega-Riz A.M.
        • Engel S.M.
        • Franceschini N.
        • Howard A.G.
        • Clowse M.E.B.
        • et al.
        Effect of pregnancy on disease flares in patients with systemic lupus erythematosus.
        Ann Rheum Dis. 2018; 77: 855-860
        • Rebić N.
        • Sayre E.C.
        • Zusman E.Z.
        • Amiri N.
        • Baldwin C.
        • De Vera M.A.
        Perinatal use and discontinuation of disease-modifying anti-rheumatic drugs and biologics in women with rheumatoid arthritis: a cohort study.
        Rheumatol Oxf Engl. 2020; 59 (Jul 1): 1514-1521
        • Bezin J.
        • Duong M.
        • Lassalle R.
        • Droz C.
        • Pariente A.
        • Blin P.
        • et al.
        The national healthcare system claims databases in France, SNIIRAM and EGB: powerful tools for pharmacoepidemiology.
        Pharmacoepidemiol Drug Saf. 2017; 26: 954-962
        • Chouchana L.
        • Beeker N.
        • Treluyer J.M.
        Is there a safety signal for dolutegravir and integrase inhibitors during pregnancy?.
        J Acquir Immune Defic Syndr 1999. 2019; 81 (01): 481-486
        • Charlton R.A.
        • Neville A.J.
        • Jordan S.
        • Pierini A.
        • Damase-Michel C.
        • Klungsøyr K.
        • et al.
        Healthcare databases in Europe for studying medicine use and safety during pregnancy.
        Pharmacoepidemiol Drug Saf. 2014; 23: 586-594
        • Mettler C.
        • Bouam S.
        • Chouchana L.
        • Terrier B.
        Validation of Takayasu arteritis, polyarteritis nodosa and Behcet's disease diagnosis codes in a French hospital database.
        Eur J Intern Med. 2021; (Aug 10;S0953-6205(21)00265-X)
        • Deshayes S.
        • Moulis G.
        • Pillebout E.
        • Aouba A.
        Audemard-Verger A. Positive predictive value of hospital discharge diagnosis code to identify immunoglobulin A vasculitis in France: a validation study.
        Eur J Intern Med. 2017; 43: e18-e19
        • Lazarewicz K.
        • Watson P.
        Giant cell arteritis.
        BMJ. 2019; 365: l1964
        • Mettler C.
        • Bouam S.
        • Liva-Yonnet S.
        • Pugnet G.
        • Terrier B.
        Validation of anti-neutrophil cytoplasm antibodies associated vasculitides diagnosis codes from the electronic health records of two French university hospitals.
        Eur J Intern Med [Internet]. 2022; (May 18 [cited 2022 May 18]; Available from:)
        • Prat M.
        • Derumeaux H.
        • Sailler L.
        • Lapeyre-Mestre M.
        • Moulis G.
        Positive predictive values of peripheral arterial and venous thrombosis codes in French hospital database.
        Fundam Clin Pharmacol. 2018; 32: 108-113
      1. Méthode de la cartographie des pathologies et des dépenses de l'Assurance Maladie [Internet]. [cited 2021 Aug 15]. Available from: https://assurance-maladie.ameli.fr/etudes-et-donnees/entree-par-theme/pathologies/cartographie-assurance-maladie/methode/methode-cartographie-pathologies-depenses-assurance-maladie.

      2. European Platform on Rare Disease Registration [Internet]. [cited 2021 Sep 28]. Available from: https://eu-rd-platform.jrc.ec.europa.eu.

        • Sangle S.R.
        • Vounotrypidis P.
        • Briley A.
        • Nel L.
        • Lutalo P.M.K.
        • Sanchez-Fernandez S.
        • et al.
        Pregnancy outcome in patients with systemic vasculitis: a single-centre matched case-control study.
        Rheumatol Oxf Engl. 2015; 54: 1582-1586
        • Pagnoux C.
        • Le Guern V.
        • Goffinet F.
        • Diot E.
        • Limal N.
        • Pannier E.
        • et al.
        Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies.
        Rheumatol Oxf Engl. 2011; 50: 953-961
        • Abisror N.
        • Mekinian A.
        • Hachulla E.
        • Lambert M.
        • Morel N.
        • Chapelon C.
        • et al.
        Analysis of risk factors for complications and adverse obstetrical outcomes in women with Takayasu arteritis: a French retrospective study and literature review.
        Clin Rheumatol. 2020; 39: 2707-2713
        • Orgul G.
        • Aktoz F.
        • Beksac M.S.
        Behcet's disease and pregnancy: what to expect?.
        J Obstet Gynaecol J Inst Obstet Gynaecol. 2018; 38: 185-188
        • Nguyen V.
        • Wuebbolt D.
        • Pagnoux C.
        • D'Souza R
        Pregnancy outcomes in women with primary systemic vasculitis: a retrospective study.
        J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2019; : 1-7
        • Götestam Skorpen C.
        • Hoeltzenbein M.
        • Tincani A.
        • Fischer-Betz R.
        • Elefant E.
        • Chambers C.
        • et al.
        The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.
        Ann Rheum Dis. 2016; 75: 795-810
        • Flint J.
        • Panchal S.
        • Hurrell A.
        • van de Venne M.
        • Gayed M.
        • Schreiber K.
        • et al.
        BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids.
        Rheumatol Oxf Engl. 2016; 55: 1693-1697
        • Harris C.
        • Marin J.
        • Beaulieu M.C.
        Rituximab induction therapy for de novo ANCA associated vasculitis in pregnancy: a case report.
        BMC Nephrol. 2018; 19 (28): 152
        • Singh P.
        • Dhooria A.
        • Rathi M.
        • Agarwal R.
        • Sharma K.
        • Dhir V.
        • et al.
        Successful treatment outcomes in pregnant patients with ANCA-associated vasculitides: a systematic review of literature.
        Int J Rheum Dis. 2018; 21: 1734-1740
        • Dalkilic E.
        • Coskun B.N.
        • Yağız B.
        • Pehlivan Y.
        A successful pregnancy in a patient with Takayasu's arteritis under tocilizumab treatment: a longitudinal case study.
        Int J Rheum Dis. 2019; 22: 1941-1944
        • Daher A.
        • Sauvetre G.
        • Girszyn N.
        • Verspyck E.
        • Levesque H.
        • Le Besnerais M
        Granulomatosis with polyangiitis and pregnancy: a case report and review of the literature.
        Obstet Med. 2020; 13: 76-82
        • Fischer-Betz R.
        • Specker C.
        • Brinks R.
        • Aringer M.
        • Schneider M.
        Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine.
        Rheumatol Oxf Engl. 2013; 52: 1070-1076
        • Saadoun D.
        • Bura-Riviere A.
        • Comarmond C.
        • Lambert M.
        • Redheuil A.
        • Mirault T.
        • et al.
        French recommendations for the management of Takayasu's arteritis.
        Orphanet J Rare Dis. 2021; 16 (Jul 21Suppl): 311
        • van Driel D.
        • Wesseling J.
        • Sauer P.J.J.
        • Touwen B.C.L.
        • van der Veer E.
        • Heymans H.S.A.
        Teratogen update: fetal effects after in utero exposure to coumarins overview of cases, follow-up findings, and pathogenesis.
        Teratology. 2002; 66: 127-140
        • Schaefer C.
        • Hannemann D.
        • Meister R.
        • Eléfant E.
        • Paulus W.
        • Vial T.
        • et al.
        Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study.
        Thromb Haemost. 2006; 95: 949-957