0961: The Use of Belimumab Before and During Pregnancy in Patients with Systemic Lupus Erythematosus: An Italian Multicenter Case-series

Francesca Crisafulli¹, MARIA CHIARA GERARDI², Maria Letizia Urban³, Margherita Zen⁴, Melissa Padovan⁵, Valentina Canti⁶, Emanuela Praino⁷, Cecilia Nalli¹, Francesca Ruffilli⁵, Francesca Saccon⁸, Micaela Fredi⁹, Liala Moschetti¹, Giacomo Emmi³, Luca Iaccarino⁴, Andrea Doria¹⁰, Leonardo Santo⁷, Franco Franceschini¹, Laura Andreoli¹ and Angela Tincani¹¹, ¹Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Brescia, Italy, ²Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia and Rheumatology Unit, ASST G.O.M. Niguarda, Milan, Milano, Italy, ³Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, ⁴Unit of Rheumatology, Department of Medicine, University of Padova, Padova, Italy, ⁵Rheumatology Unit, Azienda Ospedaliero-Universitaria of Ferrara, Ferrara, Italy, ⁶Division of Immunology, IRCCS San Raffaele Institute, Milano, Italy, ⁷Rheumatology Unit, Presidio Ospedaliero ‘Mons. Dimiccoli’, Barletta, Italy, ⁸Unit of Rheumatology, Department of Medicine, University of Padova and Fondazione Villa Salus, Mestra, Venezia, Italy, ⁹Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Manerbio, Italy, ¹⁰Rheumatology Unit, Department of Medicine (DIMED), University of Padova, Via Giustiniani, 2, 35128 Padova, Italy., Padova, Italy, ¹¹Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Gussago, Italy

Background/Purpose: Belimumab (BEL) is an anti-BLyS monoclonal antibody approved for SLE treatment. As few data about BEL use with regard to pregnancy are available, the aim of this study is to describe pregnancies exposed to BEL either preconceptionally or during pregnancy.

Methods: Data of prospectively-followed pregnancies (2014-2021) in SLE patients treated with BEL in 6 Italian centers where retrospectively collected, focusing on disease activity and outcome. Continuous data were reported as median (interquartile range).

Results: Twenty-one pregnancies in 21 SLE patients were collected (median age at conception: 34 [31-38] years; 13 in primigravidae (62%); 16 planned (76%); 18 spontaneous (86%)).

BEL (14 intravenous, 7 subcutaneous) was stopped in 3 cases preconceptionally, in 9 at positive pregnancy test and in 9 during pregnancy (4 during the 1^st trimester, 3 during the 2^nd trimester and 2 during the 3^rd trimester) (Table 1). The use of BEL during pregnancy had been agreed with the patient during preconception counselling.

Other treatments during pregnancy were: prednisone (90%); antimalarials (81%); azathioprine (48%); calcineurin-inhibitors (29%); low-dose acetylsalicylic acid (86%); low molecular weight heparin (57%).

At preconception visit, the median SLEDAI was 4 [2-4].

Three pregnancies had a flare (1 during the 2^nd and the 3^rd trimester; 2 during the 3^rd trimester), all in patients who withdrew BEL at positive pregnancy test.

Live-births were 86%.

Two miscarriages (at 7^th and 11^th week) and 1 intrauterine fetal death (at 37^th week; 21-trisomy with atrio-ventricular defect) occurred. One perinatal death occurred (in a patient with thrombotic+obstetric APS and lupus nephritis who underwent heterologous assisted reproductive technology -embryodonation- and developed eclampsia with cerebral haemorrage at 25^thweek; an urgent cesarean section was performed and the newborn died after 3 days).

Two pre-eclampsia were registered: 1 at 38^th week in a patient with history of lupus nephritis, double aPL positivity and active disease and 1 at 33^th week in a patient with cardiovascular risk factors (hypertension, obesity, cigarette smoke) and a history of pre-eclampsia in a previous pregnancy.

Four newborns were hospitalized in Intensive Care Unit (1 milk protein intolerance; 1 desaturation; 2 prematurity). One urine infection with sepsis occurred at 2 months in a baby with calico-pyelic and ureteral dilatation at birth (pre-term birth).

Eleven newborns received vaccinations according to national schedule (7 missing data).

Conclusion: In this case series, the use of BEL during pregnancy was discussed with some patients with a severe disease phenotype and at high risk of having a flare during pregnancy, in order to favor disease remission. While more data are needed, the timing of discontinuation should be individualized according to the single patient's characteristics and preferences, with a risk-benefit evaluation.

Disclosures: F. Crisafulli, UCB, Novartis, Eli Lilly; M. GERARDI, None; M. Urban, None; M. Zen, GlaxoSmithKlein(GSK); M. Padovan, None; V. Canti, None; E. Praino, None; C. Nalli, None; F. Ruffilli, None; F. Saccon, None; M. Fredi, GlaxoSmithKlein(GSK); L. Moschetti, None; G. Emmi, GlaxoSmithKlein(GSK), Sobi, Novartis; L. Iaccarino, GSK; A. Doria, GlaxoSmithKlein(GSK); L. Santo, None; F. Franceschini, None; L. Andreoli, GlaxoSmithKlein(GSK), Janssen, Novartis, UCB, Werfen; A. Tincani, GlaxoSmithKlein(GSK), UCB.