Gebelik Sırasında Monoklonal Antikor Biyolojikleri Kullanan Kadınlarda Perinatal Sonuçlar

Abstract

Amaç: Biyolojikler, sıklıkla monoklonal antikor biyolojikleri (mAbs) olarak bilinmekte olup, inflamatuvar ve otoimmün hastalıkların tedavisinde ve hastaların yaşam kalitesinde önemli iyileşmeler sağlamıştır. Hastalığın remisyonu, mAbs maruziyeti olan gebeliklerde perinatal sonuçların en güçlü belirleyicisidir. Bu çalışmanın amacı, mAbs tedavisi alan gebeliklerde maternal ve perinatal sonuçların değerlendirilmesidir Gereç ve Yöntemler: Bu çalışmada retrospektif olarak 21 tekil gebelik değerlendirildi. Gebelik boyunca ilaç kullanımı üç kategoriye ayrıldı: tüm trimesterlerde devam eden kullanım, birinci trimesterde sonlandırma ve üçüncü trimesterde sonlandırma. Monoklonal antikor biyolojikleri (mAbs), etki mekanizmaları temelinde Anti-TNF α, anti-sitokin ve anti-B hücre ajanları olarak sınıflandırıldı. Bulgular: Çalışma popülasyonunda en sık görülen altta yatan hastalık Ailevi Akdeniz Ateşi olarak saptandı. İlaç kullanımında Certolizumab pegol, en yaygın anti-TNF α ajanı; Anakinra ise en sık kullanılan anti-sitokin ajanıydı. Ortalama doğum yaşı 38±1,2 hafta ve ortalama doğum ağırlığı 3083±416 g olarak hesaplandı. Çoklu otoimmün veya inflamatuar hastalığı bulunan gebelerde, fetal büyüme kısıtlılığı, preterm doğum ve yenidoğan yoğun bakım ünitesine yatış oranları, böyle bir eşlik eden hastalığı olmayan gebelerle karşılaştırıldığında anlamlı derecede yüksek saptandı (p < 0,05). Sonuç: Çalışmamızın bulguları, birden fazla otoimmün veya inflamatuar hastalığa sahip olmanın, gebelikte olumsuz obstetrik sonuçların görülme sıklığını artırabileceğini göstermektedir.

Keywords

• Monoklonal antikor
• biyolojik
• perinatal sonuç
• anti-TNF α
• Anakinra
• Certolizumab pegol

Perinatal Outcomes in Women Exposed to Monoclonal Antibody Biologics During Pregnancy

Abstract

Objective: Biologics, often known as monoclonal antibody biologics (mAbs), have improved the treatment and quality of life for many patients with inflammatory and autoimmune diseases. Disease remission is the strongest predictor of perinatal outcomes in pregnancies exposed to monoclonal antibodies. The aim of this study was to evaluate maternal and perinatal outcomes in pregnancies receiving mAbs therapy. Materials and Methods: We retrospectively reviewed 21 singleton pregnancies. Drug exposure during pregnancy was classified as: exposure throughout all trimesters, discontinuation in the first trimester, or discontinuation in the third trimester. mAbs drugs were classified into three groups based on their mechanism:Anti-TNF α, anti-cytokine, and anti-B cell agents. Results: The most common underlying disease was Familial Mediterranean Fever. Certolizumab pegol and Anakinra were the most frequently administered anti-TNF α and anti-cytokine agents, respectively. The mean gestational age at delivery was 38±1.2 weeks, and the mean birth weight was 3083±416 g. Rates of fetal growth restriction, preterm birth, and neonatal intensive care unit admission were significantly higher in patients with multiple autoimmune or inflammatory diseases compared with patients without such conditions (p < 0.05). Conclusion: This study demonstrated that the coexistence of multiple autoimmune or inflammatory diseases may be significantly associated with a higher incidence of adverse obstetric outcomes in pregnancy.

Keywords

• Monoclonal antibody
• biologics
• perinatal outcome
• anti-TNF α
• Anakinra
• Certolizumab pegol

References

1. 1. Pham-Huy A, Top KA, Constantinescu C, Seow CH, El-Chaâr D. The use and impact of monoclonal antibody biologics during pregnancy. CMAJ 2021; 193:1129-36.
2. 2. Pham-Huy A, Sadarangani M, Huang V, Ostensen M, Castillo E, Troster SM, Vaudry W, Nguyen GC, Top KA. From mother to baby: antenatal exposure to monoclonal antibody biologics. Expert Rev Clin Immunol 2019; 15:221-9.
3. 3. Bortoli A, Pedersen N, Duricova D, D’Inca R, Gionchetti P, Panelli MR, Ardizzone S, Sanroman AL, Gisbert JP, Arena I, Riegler G, Marrollo M, Valpiani D, Corbellini A, Segato S, Castiglione F, Munkholm P. Pregnancy outcome in inflammatory bowel disease: Prospective European case-control ECCO- EpiCom study, 2003-2006. Aliment Pharmacol Ther 2011; 34:724-34.
4. 4. Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Förger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbühl C, Østensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016; 75:795-810.
5. 5. Komaki F, Komaki Y, Micic D, Ido A, Sakuraba A. Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-α use in females with immune mediated diseases; a systematic review and meta-analysis. J Autoimmun 2017; 76:38–52.
6. 6. Chambers CD, Johnson DL, Jones KL. Adalimumab and Pregnancy Outcome: The OTIS Autoimmune Diseases in Pregnancy Project. Am J Gastroenterol 2006; 101:421–2.
7. 7. Johnson DL, Jones KL, Chambers CD, Salas E. Pregnancy outcomes in women exposed to adalimumab: The OTIS autoimmune diseases in pregnancy project. Am J Gastroenterol 2008; 103:375-6.
8. 8. Mahadevan U, Long MD, Kane SV, Roy A, Dubinsky MC, Sands BE, Cohen RD, Chambers CD, Sandborn WJ. Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease. Gastroenterology 2021; 160:1131-9.

9. 9. Goeb V, Ardizzone M, Arnaud L, Avouac J, Baillet A, Belot A, Bouvard B, Coquerelle P, Dadoun S, Diguet A, Launay D, Lebouc D, Loulergue P, Mahy S, Mestat P, Mouterde G, Terrier B, Varoquier C, Verdet M, Puéchal X, Sibilia J. Recommendations for using TNF alpha antagonists and French Clinical Practice Guidelines endorsed by the French National Authority for Health. Joint Bone Spine 2013; 80:574–81.
10. 10. Luu M, Benzenine E, Doret M, Michiels C, Barkun A, Degand T, Quantin C, Bardou M. Continuous Anti-TNFα Use Throughout Pregnancy: Possible Complications For the Mother But Not for the Fetus. A Retrospective Cohort on the French National Health Insurance Database (EVASION). Am J Gastroenterol 2018; 113:1669-77.
11. 11. Brien ME, Gaudreault V, Hughes K, Hayes DJL, Heazell AEP, Girard S. A Systematic Review of the Safety of Blocking the IL-1 System in Human Pregnancy. J Clin Med 2021; 11(1):225.
12. 12. Perrotta K, Kiernan E, Bandoli G, Manaster R, Chambers C. Pregnancy outcomes following maternal treatment with rituximab prior to or during pregnancy: a case series. Rheumatol Adv Pract 2021; 5(1):rkaa074.
13. 13. Hammad I, Porter TF. An Update on Biologic Agents During Pregnancy. Clin Perinatol 2020; 47:733-42.
14. 14. Pantham P, Aye IL, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 2015; 36:709–715.
15. 15. Peraçoli JC, Rudge MV, Peraçoli MT. Tumor necrosis factor-α in gestation and puerperium of women with gestational hypertension and pre-eclampsia. Am J Reprod Immunol 2007; 57:177–85.
16. 16. Bauer S, Pollheimer J, Hartmann J, Husslein P, Aplin JD, Knöfler M. Tumor necrosis factor-α inhibits trophoblast migration through elevation of plasminogen activator inhibitor-1 in first-trimester villous explant cultures. J Clin Endocrinol Metab 2004; 89:812–22.
17. 17. Romanowska-Próchnicka K, Felis-Giemza A, Olesińska M, Wojdasiewicz P, Paradowska-Gorycka A, Szukiewicz D. The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding. Int J Mol Sci 2021; 22(6):2922.
18. 18. Anim-Nyame N, Gamble J, Sooranna SR, Johnson MR, Steer PJ. Microvascular permeability is related to circulating levels of tumour necrosis factor-α in pre-eclampsia. Cardiovasc Res 2003; 58:162–9.
19. 19. Catalano P, deMouzon SH. Maternal obesity and metabolic risk to the offspring: Why lifestyle interventions may have not achieved the desired outcomes. Int J Obes 2015; 39:642-9.