Association Between Preconception Complement Levels and Use of Hydroxychloroquine with Pregnancy Outcome in Patients with Primary Antiphospholipid Syndrome and Carriers of Antiphospholipid Antibodies: An International Multicenter Study

Daniele Lini¹, Cecilia Nalli², Laura Andreoli³, Francesca Crisafulli¹, Micaela Fredi¹, Maria Grazia Lazzaroni¹, Viktoria Bitsadze⁴, Antonia Calligaro⁵, Valentina Canti⁶, Roberto Caporali⁷, Francesco Carubbi⁸, Cecilia Chighizola⁹, Paola Conigliaro¹⁰, Fabrizio Conti¹¹, Caterina De Carolis¹², Teresa Del Ross⁵, Maria Favaro⁵, Maria Gerosa⁹, Annamaria Iuliano¹³, Jamilya Khizroeva⁴, Alexander Makatsariya⁴, Pier Luigi Meroni¹⁴, Marta Mosca¹⁵, Melissa Padovan¹⁶, Roberto Perricone¹⁰, Patrizia Rovere Querini⁶, Gian Domenico Sebastiani¹³, Chiara Tani¹⁷, Marta Tonello¹⁸, Simona Truglia¹¹, Dina Zucchi¹⁵, Franco Franceschini¹ and Angela Tincani¹⁹, ¹Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Brescia, Italy, ²ASST SPEDALI CIVILI DI BRESCIA, Brescia, Italy, ³University of Brescia, Brescia, Italy, ⁴Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia, ⁵Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy, ⁶Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy, ⁷Policlinico S. Matteo University, Pavia, Italy, ⁸Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L'Aquila, L'Aquila, Italy, ⁹University of Milan, Milan, Italy, ¹⁰Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Rome, Italy, ¹¹Lupus Clinic, Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Rome, Italy, ¹²Polymedical Center for Prevention of Recurrent Spontaneous Abortion, Rome, Italy, ¹³Rheumatology Unit, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy, ¹⁴Division of Rheumatology, ASST.G Pini, Department of Clinical Sciences and Community Health, University of Milan and Istituto Auxologico Italiano, Milan, Italy, ¹⁵Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, ¹⁶Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, Ferrara, Italy, ¹⁷Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, ¹⁸BSC, Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy, ¹⁹ASST Spedali Civili-University of Brescia, Gussago, Italy

Meeting: ACR Convergence 2021

Keywords: antiphospholipid syndrome, complement, Disease-Modifying Antirheumatic Drugs (Dmards), pregnancy

Session Information

Date: Saturday, November 6, 2021

Title: Antiphospholipid Syndrome Poster (0069–0083)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: APS is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for aPL. Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and human disease. According to some authors, Hydroxychloroquine (HCQ) can control the activation of the complement system. HCQ has been shown to improve pregnancy outcome and to reduce aPL title. In murine model of obstetrical APS, HCQ was able to prevent placental and fetal abnormalities and to lower serum C5a levels. This study was conducted to verify the effect of HCQ in a multicenter cohort of Primary APS (PAPS) and aPL carriers pregnant women and possible correlation with preconception serum C3/C4 levels.

Methods: Medical records of pregnant women with confirmed positivity for aPL antibodies attending 12 referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related adverse pregnancy outcome (APO): spontaneous abortions (< 10 weeks of gestation), fetal loss (≥10 weeks of gestation), neonatal death (death of a formed fetus alive at birth in the first 28 days of life), preterm delivery before 37 weeks of gestation, preeclampsia, eclampsia or HELLP syndrome. The presence of one or more of them were considered for the definition of gestational outcome. No patients with SLE or other autoimmune disease were included.

Results: We have analyzed 164 singleton pregnancies (22 aPL carriers – 13%) in 128 patients: all the patients were treated with combination therapy (low dose aspirin, LDA + low molecular weight heparin, LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3 and/or C4. A triple aPL positivity was observed in 54 pregnancies (40%), 14 (26%) of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ did not significantly improved the gestational outcome (14/30, 47% vs 72/134, 54%, p=0.317, ns). Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3 and/or C4 the addition of HCQ did not significantly improve pregnancy outcome (7/11, 64% vs 15/47, 32%, p=0.264, ns). We have lastly evaluated 40 pregnancies that were characterized by a high-risk profile (triple aPL positivity and complement consumption) to assess whether the administration of HCQ on the top of combination therapy during pregnancy could influence gestational outcome. HCQ significantly improved gestational outcome (7/10, 70% vs 7/30, 23%, p=0.018). This observation could not be confirmed in patients with single or double aPL positivity (p=1, ns).

Conclusion: The study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/APS high-risk patients defined as triple aPL positive, with decreased C3 and /or C4 levels. This observation confirms that HCQ exerts a beneficial effect on aPL pregnancies by complement inhibition as it was shown in animal models. In addition, our results provide the clinicians a useful tool to implement conventional treatment in patients at high risk of pregnancy complication or loss.

Disclosures: D. Lini, None; C. Nalli, None; L. Andreoli, None; F. Crisafulli, None; M. Fredi, None; M. Lazzaroni, None; V. Bitsadze, None; A. Calligaro, None; V. Canti, None; R. Caporali, Abbvie, 2, 6, BMS, 2, 6, Celltrion, 2, 6, Fresenius Kabi, 2, 6, Lilly, 2, 6, Pfizer, 2, 6, UCB, 2, 6, Sanofi, 2, 6, Sandoz, 2, 6, Novartis, 6, MSD, 2, 6, Gilead Sciences, Inc., 2, 6, Galapagos NV, 2, 6, Roche, 2, 6, SamSung-Bioepis, 2, 6; F. Carubbi, None; C. Chighizola, None; P. Conigliaro, None; F. Conti, None; C. De Carolis, None; T. Del Ross, None; M. Favaro, None; M. Gerosa, None; A. Iuliano, None; J. Khizroeva, None; A. Makatsariya, None; P. Meroni, None; M. Mosca, None; M. Padovan, None; R. Perricone, None; P. Rovere Querini, None; G. Sebastiani, None; C. Tani, None; M. Tonello, None; S. Truglia, None; D. Zucchi, None; F. Franceschini, None; A. Tincani, Novartis, 2, UCB, 2, Janssen, 2, Gsk, 6.

To cite this abstract in AMA style:

Lini D, Nalli C, Andreoli L, Crisafulli F, Fredi M, Lazzaroni M, Bitsadze V, Calligaro A, Canti V, Caporali R, Carubbi F, Chighizola C, Conigliaro P, Conti F, De Carolis C, Del Ross T, Favaro M, Gerosa M, Iuliano A, Khizroeva J, Makatsariya A, Meroni P, Mosca M, Padovan M, Perricone R, Rovere Querini P, Sebastiani G, Tani C, Tonello M, Truglia S, Zucchi D, Franceschini F, Tincani A. Association Between Preconception Complement Levels and Use of Hydroxychloroquine with Pregnancy Outcome in Patients with Primary Antiphospholipid Syndrome and Carriers of Antiphospholipid Antibodies: An International Multicenter Study [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/association-between-preconception-complement-levels-and-use-of-hydroxychloroquine-with-pregnancy-outcome-in-patients-with-primary-antiphospholipid-syndrome-and-carriers-of-antiphospholipid-antibodies/. Accessed .

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