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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]
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Can hydroxychloroquine be protective against COVID-19-associated thrombotic events ?
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The clinical significance of antiphospholipid antibodies in COVID-19 infection
Atalar, E., Erden, A., Güven, S. C., Armağan, B., Ateş, İ., Küçükşahin, O., & Omma, A. (2022) · The Journal of Infection in Developing Countries · doi:10.3855/jidc.15423 · Cited by 9
Antiphospholipid Syndrome in Patients with Venous Thromboembolism
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Self-citationGarg, S., Ferguson, S., Chewning, B. A., Gomez, S., Keevil, J. G., & Bartels, C. M. (2023) · Lupus Science & Medicine · doi:10.1136/lupus-2023-000935 · Cited by 8
Hydroxychloroquine reduces T cells activation recall antigen responses
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Antiphospholipid antibodies as potential prognostic indicators of recurrent ischemic stroke
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Antiphospholipid syndrome in cardiovascular disease and cancer
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COVID-19 Coagulopathy in a Patient With Systemic Lupus Erythematosus and Antiphospholipid Antibodies
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Viewpoint: Provoked thrombosis in antiphospholipid syndrome
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Self-citationHidroxicloroquina: Del fármaco de herencia Inca hasta la inmunología moderna
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aPLs seroconversion in antiphospholipid syndrome: from definition to clinical relevance
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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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