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Vol. 17. Issue 7.
Pages 428-429 (August - September 2021)
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Vol. 17. Issue 7.
Pages 428-429 (August - September 2021)
Letter to the Editor
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Exposure to belimumab in the first trimester of pregnancy in a young woman with systemic lupus erythematosus
Exposición a belimumab en el primer trimestre de embarazo en una mujer joven con lupus eritematoso sistémico
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Ignacio Javier Gandino
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ignaciojgandino@gmail.com

Corresponding author.
, Sophia Lutgen, María Cristina Basta, Sebastián Andrés Muñoz
División Clínica Médica, Hospital General de Agudos Juan A. Fernández, Ciudad Autónoma de Buenos Aires, Argentina
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Table 1. Cumulative pregnancy outcomes for belimumab from clinical trials, spontaneous reports, post-marketing surveillance reports, and the Belimumab Pregnancy Registry (BPR) through 08 March 2016.7
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Sr. Editor:

Mister editor, belimumab is a fully human IgG1-λ monoclonal antibody that binds to soluble human B-cell survival factor (known as BLyS or BAFF) and inhibits its biological activity.1 Belimumab was approved for treatment of systemic lupus erythematosus (SLE) because it showed superiority to the standard of care, excluding patients with active nephritis or central nervous system disease.1,2 Here, we report a case of a SLE patient that was incidentally exposed to belimumab during the first trimester of pregnancy.

A 27-year-old Caucasian female with SLE has been followed for this disease for 10 years. She began with arthritis in her hands, malar rash, oral ulcers, and serositis. Her immunology laboratory had ANA 1/1280, homogenous nuclear pattern, positive anti-dsDNA, positive anti Ro and positive lupus anticoagulant, as well as low C3 and C4 complement levels. She followed treatments with corticosteroids, hydroxychloroquine and methotrexate, with a good initial response, but effectiveness decreased over time. She started to be refractory concerning serositis, arthritis, oral ulcers and skin abnormalities related to these medications, and never had lupus nephritis or neurological compromise. Treatment with belimumab began two years before pregnancy. During this time the disease was successfully controlled, with 0 SLEDAI (SLE Disease Activity Index) points and without adverse events.

She discontinued coming to medical controls; and during this time she got pregnant. When controls were resumed, at week twelve of pregnancy, belimumab was stopped. Her pregnancy was successful, with no SLE reactivation. At week 39.6, due to oligohydramnios and lack of adequate progression, she underwent a cesarean section without any complication. The weight of the newborn was 3520 grams.

This case was an accidental condition, where the patient did not follow her medical controls and never referred to a rheumatologist for pre-pregnancy counseling.

Belimumab was well tolerated at pharmacologically active dose levels in pregnant monkeys and their infants after exposure throughout pregnancy.3 No formal clinical studies have been conducted in pregnant women.4,5

The Belimumab Pregnancy Registry (BPR) aims to evaluate pregnancy and infant outcomes in women with SLE exposed to belimumab within the 4 months prior to and/or during pregnancy.6 Data of clinical trial outcomes, spontaneous pregnancy reports, and post-marketing surveillance reports outside of the BPR have reported a total of 275 pregnancies.7 Total outcomes, BPR and non-BPR, eight were live births with apparent congenital anomaly. Table 1 shows these outcomes.7 The congenital abnormalities reported in live infants of patients exposed to belimumab included Dandy Walker syndrome, bilateral enlarged kidneys, pulmonic stenosis, mild Ebstein anomaly, unbalanced translocation between chromosomes 11 and 13, bilateral club foot, and ventricular septal defect.8

Table 1.

Cumulative pregnancy outcomes for belimumab from clinical trials, spontaneous reports, post-marketing surveillance reports, and the Belimumab Pregnancy Registry (BPR) through 08 March 2016.7

Outcomes  Non-BPRa  BPR  Total pregnancies 
Total pregnancies  275  24  299 
Lost to follow up or unknown  45  46 
Pregnancy ongoing  36  38 
Total pregnancies with known outcomes  194  21  215 
Elective termination with no apparent congenital anomaly  55  56 
Elective termination with congenital anomaly 
Total pregnancies with known outcomes excluding elective terminations  139  20  159 
Spontaneous abortion with no apparent congenital anomaly (<22wks)  47  50 
Spontaneous abortion with apparent congenital anomaly (<22wks) 
Still birth with no apparent congenital anomaly (<22wks) 
Spontaneous abortion+stillbirth/(total pregnancies with known outcomes excluding elective terminations)  52/139 (37.4%)  3/20 (15.0%)  55/159 (34.6%) 
Total live births (infants)  85  17  102 
Live births with no apparent congenital anomaly  81  13  94 
Live births with apparent congenital anomalyb  4/85 (4.7%)  4/17 (23.5%)  8/102 (7.8%) 
a

Non-BPR includes clinical trial outcomes, spontaneous pregnancy reports, and post-marketing surveillance reports outside of the Belimumab Pregnancy Registry.

b

This does not include pregnancies yet to deliver.

The EULAR points for use of belimumab before pregnancy, during pregnancy and lactation is that there is limited documentation and should be replaced before conception by other medication.9 The British Society for Rheumatology (BSR) and the British Health Professionals in Rheumatology (BHPR) guideline announces a similar statement, saying that there is insufficient data to recommend belimumab in pregnancy and an unintentional first trimester exposure is unlikely to be harmful.10

There is insufficient evidence to prove absolute safety for use belimumab during pregnancy. We need human clinical studies evaluating the use of belimumab in pregnant women to know the usefulness and safety of this drug. Over time, data from the BPR would be useful to assess safety of this agent for use in pregnancy SLE patients.5

References
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A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
Arthritis Rheum, 61 (2009), pp. 1168
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Treatment of systemic lupus erythematosus – 2013 update.
Bull Hosp Jt Dis (2013), 71 (2013), pp. 208
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D.J. Auyeung-Kim, M.N. Devalaraia, T.S. Migone, W. Cai, G.J. Chellman.
Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator.
Reprod Toxicol, 28 (2009), pp. 443-455
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Use of intravenous (IV) benlysta in pregnant patients with systemic lupus erythematosus (SLE). GlaxoSmithKline Data on File.
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Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus: a case report.
Semin Arthritis Rheum, 44 (2014), pp. 195-197
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Glakso Smith Kline (GSK) Group of Companies, (March 2016),
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Cumulative pregnancy outcomes for belimumab from clinical trials, spontaneous reports, post-marketing surveillance reports, and the Belimumab Pregnancy Registry (BPR).
Glakso Smith Kline (GSK) Group of Companies, (March 2016),
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Use of belimumab throughout 2 consecutive pregnancies in a patient with systemic lupus erythematosus.
J Rheumatol, 44 (2017), pp. 1416-1417
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C.G. Skorpen, M. Hoeltzenbein, A. Tincani, R. Fischer-Betz, E. Elefant, C. Chambers, et al.
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Ann Rheum Dis, 75 (2016), pp. 795-810
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J. Flint, S. Panchal, A. Hurrell, M. van de Venne, M. Gayed, K. Schreiber, 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.
Rheumatology (Oxford), 55 (2016), pp. 1693-1697
Copyright © 2020. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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