The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome
Abstract
Hydroxychloroquine (HCQ) was suggested to play a role in lowering antiphospholipid antibody titers and preventing thrombotic recurrences in patients with systemic lupus erythematosus, but few data are available in patients with primary antiphospholipid syndrome (PAPS). In this retrospective, propensity score-matched cohort study, we evaluated the impact of HCQ on aPL titers and the incidence of thrombotic events in 57 exposed patients compared to 57 not exposed patients. These were matched for sex/type of disease onset/follow-up duration, age at the beginning of the follow-up ±10 years and initial date of the follow-up ±5 years. At baseline, no significant differences in demographical, clinical and serological features were observed between the two groups except for positive anti-extractable nuclear antigen antibodies (21 % in HCQ exposed vs 0 % in HCQ not exposed, P = 0.001). Both the levels of IgG anti-cardiolipin and IgG/IgM anti-β2-glycoprotein I (anti-β2GPI) were significantly reduced at end of follow-up compared to the baseline in HCQ-exposed patients, while there were no differences in the other group. Moreover, anti-β2GPI IgG titers were significantly decreased when the end of follow-up was compared between the two groups (P < 0.002). Among patients with a history of thrombosis, the annual incidence of recurrence was 1.16 % in HCQ exposed and 1.71 % in not exposed patients, with a significant reduction in the incidence of arterial events (0 vs 1.14 %). This study shows a strong reduction in aPL titers together with an apparent decrease in the incidence of arterial thrombosis recurrence in PAPS patients treated with HCQ.
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In the citing paper
“Three clinical studies met the inclusion criteria, comprising a total of 164 adult patients with thrombotic primary antiphospholipid syndrome (PAPS), of whom 82 received hydroxychloroquine (HCQ) in addition to standard antithrombotic therapy and 82 received standard therapy alone [8–10].”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“In the multicenter retrospective propensity score-matched cohort by Nuri et al., 57 HCQ-treated patients with PAPS were matched to 57 controls without HCQ exposure and followed longitudinally [9].”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“Across studies, patients were predominantly female (approximately 70–80% women, when reported), and all had a documented history of objectively confirmed thrombosis fulfilling APS classification criteria.”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“High-risk antiphospholipid antibody profiles (lupus anticoagulant positivity and/or double aPL positivity) were frequent, although reporting of triple positivity was heterogeneous [8–10].”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“One study was a randomized prospective trial conducted in Greece [8], one a retrospective multicenter propensity score-matched cohort from Italy [9], and one a prospective non-randomized controlled study from France [10].”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“Notably, arterial thrombotic recurrences occurred exclusively in the control group, whereas no arterial events were observed among HCQ-treated patients during follow-up.”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“Among patients with prior thrombosis, the annual incidence of thrombotic recurrence was 1.16% in the HCQ group versus 1.71% in the control group, corresponding to a relative risk reduction of approximately 32%.”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“In parallel, HCQ exposure was associated with a statistically significant reduction in IgG anticardiolipin and anti-β2-glycoprotein I antibody titers, whereas antibody levels remained largely unchanged in controls [9].”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“The majority of patients had experienced venous thromboembolism as the index event, while arterial thrombosis accounted for a smaller but clinically relevant proportion of cases.”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
In the citing paper
“The absence of a bleeding signal attributable to HCQ in any of the included studies further supports its favorable risk–benefit profile [8–10].”
From Hydroxychloroquine as an Adjunct Therapy for Secondary Thrombosis Prevention in Primary Antiphospholipid Syndrome: A Systematic Review and Meta-analysis (2026) · cites this paper as [9]
Citations
Cites
MIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203
Self-citationUpdate of the guidelines for lupus anticoagulant detection
PENGO, V., TRIPODI, A., REBER, G., RAND, J. H., ORTEL, T. L., GALLI, M., & DE GROOT, P. G. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03555.x · Cited by 1,197
Self-citationCervera, R., Serrano, R., Pons-Estel, G. J., Ceberio-Hualde, L., Shoenfeld, Y., de Ramón, E., Buonaiuto, V, Jacobsen, S., Zeher, M. M., Tarr, T., et al. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204838 · Cited by 974
Self-citationThe Canadian Hydroxychloroquine Study Group* (1991) · New England Journal of Medicine · doi:10.1056/nejm199101173240303 · Cited by 676
Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome
PENGO, V., RUFFATTI, A., LEGNANI, C., GRESELE, P., BARCELLONA, D., ERBA, N., TESTA, S., MARONGIU, F., BISON, E., DENAS, G., et al. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03674.x · Cited by 632
Self-citationRuiz-Irastorza, G., Cuadrado, M., Ruiz-Arruza, I., Brey, R., Crowther, M., Derksen, R., Erkan, D., Krilis, S., Machin, S., Pengo, V, et al. (2011) · Lupus · doi:10.1177/0961203310395803 · Cited by 506
Self-citationEffect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus
Ruiz-Irastorza, G., Egurbide, M.-V., Pijoan, J.-I., Garmendia, M., Villar, I., Martinez-Berriotxoa, A., Erdozain, J.-G., & Aguirre, C. (2006) · Lupus · doi:10.1177/0961203306071872 · Cited by 411
Petri, M., Lakatta, C., Magder, L., & Goldman, D. (1994) · The American Journal of Medicine · doi:10.1016/0002-9343(94)90151-1 · Cited by 323
Jung, H., Bobba, R., Su, J., Shariati‐Sarabi, Z., Gladman, D. D., Urowitz, M., Lou, W., & Fortin, P. R. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27289 · Cited by 291
Hydroxychloroquine use in the Baltimore Lupus Cohort: effects on lipids, glucose and thrombosis
Petri, M. (1996) · Lupus · doi:10.1177/0961203396005001051 · Cited by 259
Kaiser, R., Cleveland, C. M., & Criswell, L. A. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.093013 · Cited by 244
Wallace, D. J., METZGER, A. L., Stecher, V. J., Turnbull, B. A., & Kern, P. A. (1990) · The American Journal of Medicine · doi:10.1016/0002-9343(90)90345-e · Cited by 230
Rand, J. H., Wu, X.-X., Quinn, A. S., Chen, P. P., Hathcock, J. J., & Taatjes, D. J. (2008) · Blood · doi:10.1182/blood-2008-03-144204 · Cited by 215
Petri, M. (2011) · Current Rheumatology Reports · doi:10.1007/s11926-010-0141-y · Cited by 206
Goldman, F. D., Gilman, A. L., Hollenback, C., Kato, R. M., Premack, B. A., & Rawlings, D. J. (2000) · Blood · doi:10.1182/blood.v95.11.3460 · Cited by 181
Dr., N. L. P., & Levine, C. C. (2004) · Springer eBooks · doi:10.1007/3-540-29668-9_242 · Cited by 181
Biochemical characterization of ADP-ribose polymer metabolism in SLE
Chen, H.-Y., Pertusi, R. M., Kirkland, J., Rubin, B. R., & Jacobson, E. L. (1996) · Lupus · doi:10.1177/096120339600500105 · Cited by 162
Antimalarial agents: Closing the gate on toll‐like receptors?
Lafyatis, R., York, M. R., & Marshak‐Rothstein, A. (2006) · Arthritis & Rheumatism · doi:10.1002/art.22157 · Cited by 153
Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?
Balestrieri, G., Tincani, A., Spatola, L., Allegri, F., Prati, E., Cattaneo, R., Valesini, G., Papa, N. D., & Meroni, P. L. (1995) · Lupus · doi:10.1177/096120339500400208 · Cited by 153
Self-citationBorba, E. F., & Bonfá, E. (2001) · PubMed · Cited by 145
Hydroxychloroquine Compared with Placebo in Rheumatoid Arthritis
Clark, P., Casas, E., Tugwell, P., Medina, C., Gheno, C., Tenorio, G., & Orozco, J. A. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-119-11-199312010-00002 · Cited by 140
Kyburz, D., Brentano, F., & Gay, S. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0292 · Cited by 136
Molad, Y., Gorshtein, A., Wysenbeek, A. J., Guedj, D., Majadla, R., Weinberger, A., & Amit-Vazina, M. (2002) · Lupus · doi:10.1191/0961203302lu203ra · Cited by 134
Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients
Schmidt‐Tanguy, A., Voswinkel, J., Henrion, D., Subra, J. F., Loufrani, L., Rohmer, V., Ifrah, N., & Belizna, C. (2013) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12363 · Cited by 132
Tincani, A., Allegri, F., Balestrieri, G., Reber, G., Sanmarco, M., Meroni, P. L., & Boffa, M. (2004) · Thrombosis Research · doi:10.1016/j.thromres.2004.06.035 · Cited by 128
Self-citationHo, K. T., Ahn, C. W., Alarcón, G. S., Baethge, B. A., Tan, F. K., Roseman, J., Bastian, H. M., Fessler, B. J., McGwin, G., Vilá, L. M., et al. (2005) · Rheumatology · doi:10.1093/rheumatology/kei014 · Cited by 128
Does hydroxychloroquine sulfate prevent clot formation in systemic lupus erythematosus?
Wallace, D. J. (1987) · Arthritis & Rheumatism · doi:10.1002/art.1780301219 · Cited by 124
Platelet-Inhibiting Drugs in the Prevention of Clinical Thrombotic Disease
Genton, E., Gent, M., Hirsh, J., et al. (1975) · New England Journal of Medicine · doi:10.1056/nejm197512042932305 · Cited by 111
Wallace, D. J., Linker‐Israeli, M., METZGER, A. L., & Stecher, V. J. (1993) · Lupus · doi:10.1177/0961203393002001041 · Cited by 111
BRODER, A., & PUTTERMAN, C. (2013) · The Journal of Rheumatology · doi:10.3899/jrheum.120157 · Cited by 102
The efficacy of antimalarials in systemic lupus erythematosus.
Nayak, V., & Esdaile, J. M. (1993) · PubMed · Cited by 98
On the inhibitory effect of chloroquine on blood platelet aggregation
Jančinová, V., Nosál, R., & Petríková, M. (1994) · Thrombosis Research · doi:10.1016/0049-3848(94)90270-4 · Cited by 84
The Clinical Significance of Autoantibody Profiles in Patients with Systemic Lupus Erythematosus
Thompson, D., Juby, A. G., & Davis, P. J. (1993) · Lupus · doi:10.1177/096120339300200104 · Cited by 84
Martin, A., & Reichlin, M. (1996) · Lupus · doi:10.1177/096120339600500106 · Cited by 82
Antinucleosome antibodies in primary antiphospholipid syndrome: A hint at systemic autoimmunity?
Andréoli, L., Pregnolato, F., Burlingame, R. W., Allegri, F., Rizzini, S., Fanelli, V., Radice, A., Corace, C., Sinico, R. A., Meroni, P. L., et al. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2007.11.004 · Cited by 60
Self-citationMetabolism of chloroquine and hydroxychloroquine in albino and pigmented rats
McChesney, E. W., Banks, W. F., & Sullivan, D. (1965) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(65)90050-5 · Cited by 60
Lombard-Platlet, S., Bertolino, P., Deng, H., et al. (1993) · PubMed · Cited by 55
Antiphospholipid Syndrome Clinical Research Task Force Report
Erkan, D., Derksen, R. H. W. M., Levy, R. A., Machin, S. J., Ortel, T. L., Pierangeli, S. S., Roubey, R. A. S., & Lockshin, M. D. (2011) · Lupus · doi:10.1177/0961203310395053 · Cited by 42
Platelet-Inhibiting Drugs in the Prevention of Clinical Thrombotic Disease
Genton, E., Gent, M., Hirsh, J., et al. (1975) · New England Journal of Medicine · doi:10.1056/nejm197512182932506 · Cited by 30
Hydroxychloroquine treatment of rheumatoid arthritis
Rynes, R. I. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90357-9 · Cited by 27
APS—More Systemic Disease than SLE
Shoenfeld, Y. (2007) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-007-0005-z · Cited by 24
The efficacy of antimalarials in systemic lupus erythematosus
Nayak, V., & Jm, E. (1996) · Lupus · doi:10.1177/0961203396005001061 · Cited by 10
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Schrezenmeier, E., & Dörner, T. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0372-x · Cited by 1,468
Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome
Pengo, V., Denas, G., Zoppellaro, G., Jose, S. P., Hoxha, A., Ruffatti, A., Andreoli, L., Tincani, A., Cenci, C., Prisco, D., et al. (2018) · Blood · doi:10.1182/blood-2018-04-848333 · Cited by 822
Self-citationOrdi-Ros, J., Sáez-Comet, L., Pérez-Conesa, M., Vidal, X., Riera-Mestre, A., Castro-Salomó, A., Cuquet-Pedragosa, J., Ortiz-Santamaria, V., Mauri-Plana, M., Solé, C., et al. (2019) · Annals of Internal Medicine · doi:10.7326/m19-0291 · Cited by 324
Diagnosis and management of the antiphospholipid syndrome
Chaturvedi, S., & McCrae, K. R. (2017) · Blood Reviews · doi:10.1016/j.blre.2017.07.006 · Cited by 195
McDonnell, T. C. R., Wincup, C., Buchholz, I., Pericleous, C., Giles, I., Ripoll, V. M., Cohen, H., Delcea, M., & Rahman, A. (2019) · Blood Reviews · doi:10.1016/j.blre.2019.100610 · Cited by 176
Metadata
- Authors
- Nuri, E., Taraborelli, M., Andreoli, L., Tonello, M., Gerosa, M., Calligaro, A., Argolini, L. M., Kumar, R., Pengo, V., Meroni, P. L., Ruffatti, A., & Tincani, A.
- Affiliations
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- University of Padua (IT)
- University of Milan (IT)
- ORCID
- Venue
- Immunologic Research
- Published
- 2016-07-13
- Volume
- 65
- Issue
- 1
- Pages
- 17-24
- ISSN
- 0257-277X (ISSN-L)
- 1559-0755
- OpenAlex
- W2460218540
- Semantic Scholar
- 7a1185c5b341f66380f80a3cce640b70c57dc651
- Cited by
- 123
- References
- 41
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 13 · 2023: 15 · 2022: 12 · 2021: 13 · 2020: 27 · 2019: 13 · 2018: 14 · 2017: 3 · 2016: 1
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunologic Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Rheumatology › Vasculitis and related conditions
- Keywords
- hydroxychloroquine, primary antiphospholipid syndrome, antiphospholipid antibodies, anti-beta2-glycoprotein I antibodies, anticardiolipin antibodies, recurrent thrombosis, arterial thrombosis, long-term drug therapy
- MeSH terms
- Adult, Antibodies, Antinuclear, Blood Glucose, Cholesterol, Female, Humans, Hydroxychloroquine, Immunoglobulin G, Immunoglobulin M, Male, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Antibodies, Anticardiolipin, Antirheumatic Agents, beta 2-Glycoprotein I
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