ABS0383 PREGNANCY OUTCOMES IN PATIENTS EXPOSED TO VOCLOSPORIN: A SUMMARY OF AVAILABLE DATA FROM CLINICAL TRIALS AND POST-MARKETING SOURCES

Background: Published data suggest active lupus nephritis (LN) in pregnancy is strongly associated with poor maternal and fetal outcomes, including renal flare, gestational hypertension, pre-eclampsia, newborn prematurity, intrauterine growth retardation, and spontaneous miscarriage [1, 2]. Pregnant patients with systemic lupus erythematosus (SLE) and active LN have demonstrated a 6-fold increase in fetal loss and a 3-fold increase in poor pregnancy outcomes compared to patients with SLE without a history of LN [3]. Therapeutic agents including mycophenolate mofetil (MMF), commonly used in LN, have also been linked to birth defects and pregnancy loss. Therefore, it is necessary to carefully balance disease control with pregnancy management, to minimize potential harm to the fetus. Voclosporin, a second generation calcineurin inhibitor, was approved for use in active LN in the United States in January 2021, the European Union in September 2022, and Japan in 2024. Per the approved labeling in the US and European Union, use in pregnant women should be avoided[4, 5]. The approved Japanese label states voclosporin should be administered to pregnant women or women suspected of being pregnant only if the expected therapeutic benefit is thought to outweigh any possible risk [6]. In embryofetal developmental studies of pregnant rats and rabbits during the period of organogenesis, no treatment-related fetal malformations were observed [4]. During the clinical development program of voclosporin, patients were excluded if pregnant, breastfeeding, or if they were of childbearing potential and not using adequate contraceptive precautions. Available data on the use of voclosporin in pregnant patients are insufficient to assess the drug-associated risk for adverse maternal or fetal outcomes. There have been reports of pregnancy in patients exposed to voclosporin during clinical trials and in the post-marketing setting. Objectives: Our objective was to describe the available pregnancy outcomes following voclosporin exposure from these sources. Methods: Data were collected from the voclosporin clinical trials (plaque psoriasis [NCT00244842], uveitis [NCT01243983], and LN [AURA-LV, NCT02141672; AURORA 1, NCT03021499]) and the Aurinia Safety Database containing post-marketing/spontaneous reports of pregnancy up to December 31 st , 2024. Results: A total of 66 pregnancies in 64 female patients of child-bearing age have been reported from the clinical development program and post-marketing reports with voclosporin. Clinical Trials During the clinical development program for voclosporin, ten pregnancies in ten patients were reported. Consistent with the study protocols, all patients discontinued voclosporin when pregnancy was detected. Five patients treated with voclosporin became pregnant during the clinical trials for plaque psoriasis and uveitis. Four resulted in live births, and the fifth pregnancy was lost to follow-up and later reported as terminated with no further information available. Five pregnancies were also reported during the clinical trials for LN. Of these cases, three ended with elective abortion, one was lost to follow up, and one pregnancy resulted in a live birth. Post-marketing reports As of December 31 st , 2024, 56 reports of pregnancy in 54 LN patients treated with voclosporin in the United States have been received. Pregnancy outcomes were not available in the majority of the reports (68%, n=38). Of the remaining 18 reports, ten ended with miscarriage (including one patient who had two miscarriages), three with elective abortion, and one with stillbirth; four pregnancies resulted in live births. No congenital anomalies were reported when pregnancy outcomes were provided. Conclusion: Active LN in pregnancy is associated with an increased risk of adverse maternal and fetal outcomes, and observations from this limited cohort reflect the overall challenges faced by female patients of child-bearing age with active LN. The limited data presented here are insufficient to draw conclusions regarding the use of voclosporin during pregnancy, and additional research is needed to better characterize maternal and fetal outcomes following voclosporin exposure. REFERENCES: [1] Clowse ME. Rheum Dis Clin North Am . May 2007;33(2):237-52. [2] Tan B, So PN, Krishnan A, et al. 2023;5(11):100724. [3] Lucas A, Eudy AM, Gladman D, et al. Lupus . Oct 2022;31(11):1401-1407. [4] LUPKYNIS [package insert]. Rockville, MD: Aurinia Pharma US, Inc.; 2021. Revised: 4/2024. [5] LUPKYNIS [SmPC]. Windsor, UK; Otsuka Pharmaceuticals (UK) Ltd.; 2022. Revised: 8/20/2024. [6] LUPKYNIS [package insert]. Tokyo, Japan; Otsuka Pharmaceutical Co, Ltd.; 2024. Acknowledgements: NIL . Disclosure of Interests: Eugenia Yupei Chock: None declared, Tasim Begum Aurinia Pharmaceuticals Inc., Aurinia Pharmaceuticals Inc., Kathryn Dao Aurinia Pharmaceuticals Inc., Aurinia Pharmaceuticals Inc., Catherine Zhou Aurinia Pharmaceuticals Inc., Michelle Dardeno Aurinia Pharmaceuticals Inc., Aurinia Pharmaceuticals Inc. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.