EULAR Abstract Archive

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POS0721 (2022)

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

D. Lini¹, C. Nalli¹, L. Andreoli¹, F. Crisafulli¹, M. Fredi¹, M. G. Lazzaroni¹, V. Bitsadze², A. Calligaro³, V. Canti⁴, R. Caporali^5,6, F. Carubbi⁷, C. Chighizola^8,9, P. Conigliaro¹⁰, F. Conti¹¹, C. De Carolis¹², T. Del Ross³, M. Favaro³, M. Gerosa¹³, A. Iuliano¹⁴, J. Khizroeva², A. Makatsariya², P. L. Meroni¹⁵, M. Mosca¹⁶, M. Padovan¹⁷, R. Perricone¹⁰, P. Rovere-Querini⁴, G. D. Sebastiani¹⁴, C. Tani¹⁶, M. Tonello¹⁸, S. Truglia¹¹, D. Zucchi¹⁹, F. Franceschini¹, A. Tincani^1,2

¹Spedali Civili di Brescia, Rheumatology and Clinical Immunology, Brescia, Italy
²I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Department of Obstetrics and Gynecology, Moscow, Russian Federation
³University of Padua, Rheumatology Unit, Department of Medicine, Padua, Italy
⁴IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Milan, Italy
⁵Division of Clinical Rheumatology, ASST Gaetano Pini-CTO Institute, Milan, Italy
⁶Università degli Studi di Milano, Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, Milan, Italy
⁷School of Medicine, University of L’Aquila, Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, L’Aquila, Italy
⁸University of Milan, Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, Milan, Italy
⁹ASST G. Pini & CTO, Pediatric Rheumatology Unit, Milan, Italy
¹⁰University of Rome Tor Vergata, Rheumatology, Allergology and Clinical Immunology, Department of “Medicina dei Sistemi”, Rome, Italy
¹¹Sapienza Università di Roma, Lupus Clinic, Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Rome, Italy
¹²Polymedical Center for Prevention of Recurrent Spontaneous Abortion, Rome, Italy
¹³University of Milan, Division of Rheumatology, Department of Clinical Sciences and Community Health, Ospedale Gaetano Pini, Milan, Italy
¹⁴Azienda Ospedaliera San Camillo-Forlanini, Rheumatology Unit, Rome, Italy
¹⁵University of Milan and Istituto Auxologico Italiano, Division of Rheumatology, ASST.G Pini, Department of Clinical Sciences and Community Health, Milan, Italy
¹⁶University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy
¹⁷University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, Rheumatology Unit, Department of Medical Sciences, Ferrara, Italy
¹⁸University of Padua, BSC, Rheumatology Unit, Department of Medicine, Padua, Italy
¹⁹University of Pisa, Rheumatology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy

Background: Antiphospholipid Syndrome (APS) is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for antiphospholipid antibodies (aPL). Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and several groups investigated the significance of complement levels in human disease. C3 and C4 serum levels were assessed in several cohorts of pregnant patients with APS and/or aPL positivity in order to relate complement consumption with adverse pregnancy outcome (APO).

According to some authors, hydroxychloroquine (HCQ) can control the activation of the complement system, improve pregnancy outcome and reduce aPL title.

Objectives: This study was designed to verify the effect of HCQ in addition to low dose aspirin (LDA) + low molecular weight heparin (LMWH) treatment in a multicenter cohort of primary APS (PAPS) and aPL carriers pregnant women and the possible correlation with preconception serum C3/C4 levels.

Methods: Medical records of pregnant women with confirmed positivity for aPL antibodies attending twelve referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related 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 (hemolysis, elevated liver enzymes, and low platelet).

Results: We have analyzed 164 singleton PAPS/aPL carrier pregnancies (22 aPL carriers - 13%) in 128 patients: all were treated with combination therapy (LDA+LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3/C4. A triple aPL positivity was observed in 54 pregnancies, 14 of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ had not significantly improved the gestational outcome. Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3/C4 levels the addition of HCQ had not significantly improved pregnancy outcome. We have lastly evaluated 40 pregnancies with a high-risk profile (triple aPL positivity and complement consumption), in which we have found that HCQ significantly improved gestational outcome (p=0.018, Table 1 ).

Table 1.

Relationship between APO, therapy during pregnancy and risk profile.

	All pregnancies (n=164)			Reduced C3/C4 (n=58)			Triple aPL+ and reduced C3/C4 (n=40)
	LDA+LMWH (n, %)	LDA+LMWH+HCQ (n, %)	p	LDA+LMWH (n, %)	LDA+LMWH+HCQ	p	LDA+LMWH	LDA+LMWH+HCQ	p
	LDA+LMWH (n, %)	LDA+LMWH+HCQ (n, %)	p	LDA+LMWH (n, %)	(n, %)	p	(n, %)	(n, %)	p
APO	62 (46%)	16 (53%)	ns	32 (68%)	4 (36%)	ns	23 (77%)	3 (30%)	0.018
No APO	72 (54%)	14 (47%)	ns	15 (32%)	7 (64%)	ns	7 (23%)	7 (70%)	0.018
Total	134	30		47	11		30	10

This observation could not be confirmed in patients with single or double aPL positivity.

Conclusion: The study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/PAPS high-risk patients. 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.

REFERENCES:

[1]De Carolis S, et al. Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment? Autoimmun Rev 2015;14:760-2.

[2]Mekinian A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in antiphospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 2015;40:498-502.

[3]Mekinian A et al. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? Autoimmun Rev 2015;14:23-9.

Disclosure of Interests: None declared

Citation: , volume 81, supplement 1, year 2022, page 643

Session: SLE, Sjön’s and APS – treatment (POSTERS only)

version:	1.02