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Article ; Online: Anticoagulant and non-anticoagulant therapy in thrombotic antiphospholipid syndrome: old drugs and new treatment targets.

Ruiz-Irastorza, Guillermo / Tektonidou, Maria G / Khamashta, Munther

2024 Volume 63, Issue SI, Page(s) SI96–SI106

Abstract: In this review, we discuss the current evidence on classic and newer oral anticoagulant therapy, older drugs such as HCQ and statins, and new potential treatment targets in APS. Vitamin K antagonists (VKAs) remain the cornerstone treatment for thrombotic ...

Abstract	In this review, we discuss the current evidence on classic and newer oral anticoagulant therapy, older drugs such as HCQ and statins, and new potential treatment targets in APS. Vitamin K antagonists (VKAs) remain the cornerstone treatment for thrombotic events in APS. In patients fulfilling criteria for definite APS presenting with a first venous thrombosis, treatment with VKAs with a target international normalized ratio (INR) 2.0-3.0 is recommended. In patients with arterial thrombosis, treatment with VKA with target INR 2.0-3.0 or 3.0-4.0 is recommended by recent guidelines, considering the individual's bleeding and thrombosis recurrence risk. A combination of VKAs and low-dose aspirin (75-100 mg/daily) may also be considered. According to available evidence direct oral anticoagulants should be avoided in patients with arterial thrombosis and/or those with triple aPL positivity. Adjunctive treatment with HCQ and/or statins can be considered, especially in anticoagulation treatment-refractory APS. Potential targeted treatments in APS include B-cell targeting, complement inhibition, mammalian target of rapamycin inhibition, IFN targeting, adenosine receptors agonists, CD38 targeting or chimeric antigen receptor T-cell therapy. The safety and efficacy of these treatment targets needs to be examined in well-designed randomized controlled trials.
MeSH term(s)	Humans ; Anticoagulants/therapeutic use ; Antiphospholipid Syndrome/drug therapy ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Thrombosis/chemically induced ; Hemorrhage
Chemical Substances	Anticoagulants ; Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2024-02-07
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead538
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Article ; Online: Prednisone in systemic lupus erythematosus: taper quickly, withdraw slowly.

Ruiz-Irastorza, Guillermo

Rheumatology (Oxford, England)

2021 Volume 60, Issue 12, Page(s) 5489–5490

MeSH term(s)	Drug Therapy, Combination ; Humans ; Lupus Erythematosus, Systemic/drug therapy ; Prednisone/therapeutic use
Chemical Substances	Prednisone (VB0R961HZT)
Language	English
Publishing date	2021-03-26
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keab347
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Article ; Online: Systemic lupus erythematosus and glucocorticoids: A never-ending story?

Paredes-Ruiz, Diana / Ruiz-Irastorza, Guillermo / Amoura, Zahir

Best practice & research. Clinical rheumatology

2023 , Page(s) 101873

Abstract: Glucocorticoids (GCs) continue to be essential agents for the management of systemic lupus erythematosus, since there are no other drugs able to active remission of active disease so rapidly. However, their potential for causing irreversible damage ... ...

Abstract	Glucocorticoids (GCs) continue to be essential agents for the management of systemic lupus erythematosus, since there are no other drugs able to active remission of active disease so rapidly. However, their potential for causing irreversible damage greatly limit their use. Fortunately, some strategies may help take advantage of their huge anti-inflammatory power while limiting GC-induced side effects. This article reviews the pharmacological basis of GC action and their translation into the clinical ground. We also offer the practical approach for the use of GC in induction and maintenance therapy as well as the strategies for GC withdrawal of the respective practice of the authors. The three main basic principles are a) using methyl-prednisolone pulses to induce remission not only in severe disease; b) limiting initial doses of prednisone to ≤30 mg/d, with rapid tapering to ≤5 mg/d, which should be the dose for maintenance therapy; and c) individualizing the decision and the strategy to withdraw GCs. Long-term therapy with HCQ and the early introduction of immunosuppressive treatment would help achieve these objectives.
Language	English
Publishing date	2023-11-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052323-3
ISSN	1532-1770 ; 1521-6942
ISSN (online)	1532-1770
ISSN	1521-6942
DOI	10.1016/j.berh.2023.101873
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Article ; Online: Is it safe to withdraw low-dose glucocorticoids in SLE patients in remission?

Mathian, Alexis / Arnaud, Laurent / Ruiz-Irastorza, Guillermo

Autoimmunity reviews

2023 Volume 23, Issue 1, Page(s) 103446

Abstract: Glucocorticoids (GCs) remain a cornerstone of the treatment of Systemic Lupus Erythematosus (SLE). Numerous studies have emphasized the risk of damage accrual in SLE patient treated with GC, but currently, it is not possible to dissociate favorable and ... ...

Abstract	Glucocorticoids (GCs) remain a cornerstone of the treatment of Systemic Lupus Erythematosus (SLE). Numerous studies have emphasized the risk of damage accrual in SLE patient treated with GC, but currently, it is not possible to dissociate favorable and undesirable effects of GCs because their underlying mechanisms are entangled at the molecular level. Here, we review whether available data suggest that it is possible, feasible and desirable to taper and discontinue GC treatment in SLE. The main potential concern with GC withdrawal is the risk of SLE flare, which is strongly associated with increased organ damage, mortality, healthcare costs, decreased quality of life and work productivity. While most studies have assumed the cut off point for low doses (e.g. 7.5/mg/d) as the limit for safety, it is still controversial whether lower doses may influence damage accrual long-term. Also, a recent randomized trial has shown that a daily dose of 5 mg of prednisone in SLE patients in short-term remission can prevent up to 50-75% of flares, with an acceptable safety profile. However, this treatment is not mandatory for all patients. Yet, several observational studies highlight that discontinuation of GC is associated with lower damage accrual. Currently, we do not have a reliable method to identify patients who may require long-term low-dose GC. Therefore, further research is needed to identify a subgroup at high risk of relapse who would benefit from continuing prednisone. In the meantime, when considering the discontinuation of very low-dose prednisone, the decision must be individualized, as HCQ and conventional immunosuppressive agents are not without risk of side effects.
MeSH term(s)	Humans ; Glucocorticoids/adverse effects ; Prednisone/therapeutic use ; Quality of Life ; Lupus Erythematosus, Systemic/complications ; Immunosuppressive Agents/therapeutic use ; Severity of Illness Index
Chemical Substances	Glucocorticoids ; Prednisone (VB0R961HZT) ; Immunosuppressive Agents
Language	English
Publishing date	2023-09-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2023.103446
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Article ; Online: Can we effectively treat lupus and reduce the side-effects of glucocorticoids?

Ruiz-Irastorza, Guillermo

The Lancet. Rheumatology

2019 Volume 2, Issue 1, Page(s) e3–e5

Language	English
Publishing date	2019-11-25
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(19)30132-8
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Article ; Online: Treating systemic lupus erythematosus in the 21st century: new drugs and new perspectives on old drugs.

Ruiz-Irastorza, Guillermo / Bertsias, George

Rheumatology (Oxford, England)

2021 Volume 59, Issue Suppl5, Page(s) v69–v81

Abstract: Besides treating acute flares, the management of SLE should aim at preventing organ damage accrual and drug-associated harms, improving health-related quality of life and prolonging survival. At present, therapy is based on combinations of antimalarials ( ...

Abstract	Besides treating acute flares, the management of SLE should aim at preventing organ damage accrual and drug-associated harms, improving health-related quality of life and prolonging survival. At present, therapy is based on combinations of antimalarials (mainly HCQ), considered the backbone of SLE treatment, glucocorticoids and immunosuppressive drugs. However, these regimens are not universally effective and a substantial degree of damage can be caused by exposure to glucocorticoids. In this review we provide a critical appraisal of the efficacy and safety of available treatments as well as a brief discussion of potentially novel compounds in patients with SLE. We emphasize the use of methylprednisolone pulses for moderate-severe flares, followed by low-moderate doses of oral prednisone with quick tapering to maintenance doses of ≤5 mg/day, as well as the prompt institution of immunosuppressive drugs in the setting of severe disease but also as steroid-sparing agents. Indications for the use of biologic agents, namely belimumab and rituximab, in refractory or organ-threatening disease are also presented. We conclude by proposing evidence- and experience-based treatment strategies tailored to the clinical scenario and prevailing organ involvement that can aid clinicians in managing this complex disease.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Antimalarials/adverse effects ; Antimalarials/therapeutic use ; Glucocorticoids/adverse effects ; Glucocorticoids/therapeutic use ; Humans ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/therapeutic use ; Lupus Erythematosus, Systemic/drug therapy ; Rituximab/therapeutic use ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antimalarials ; Glucocorticoids ; Immunosuppressive Agents ; Rituximab (4F4X42SYQ6) ; belimumab (73B0K5S26A)
Language	English
Publishing date	2021-01-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keaa403
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Article ; Online: Balancing risks and benefits in the use of hydroxychloroquine and glucocorticoids in systemic lupus erythematosus.

Paredes-Ruiz, Diana / Martin-Iglesias, Daniel / Ruiz-Irastorza, Guillermo

Expert review of clinical immunology

2023 Volume 20, Issue 4, Page(s) 359–373

Abstract: Introduction: Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly ... ...

Abstract	Introduction: Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly regarding the dose. Areas covered: We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence. Expert opinion: HCQ is the backbone therapy for SLE, and a judicious use must be accomplished, using doses that allow a good control of lupus without compromising the safety of treatments very much prolonged over the time. Stable doses of 200 mg/day seem to accomplish both conditions. GCs should be used more judiciously, with methyl-prednisolone pulses as the main therapy for inducing rapid remission and doses ≤5-2.5 mg/day be never exceeded in long-term maintenance treatments.
MeSH term(s)	Humans ; Hydroxychloroquine/adverse effects ; Glucocorticoids/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Lupus Erythematosus, Systemic/drug therapy ; Risk Assessment ; Antirheumatic Agents/therapeutic use
Chemical Substances	Hydroxychloroquine (4QWG6N8QKH) ; Glucocorticoids ; Immunosuppressive Agents ; Antirheumatic Agents
Language	English
Publishing date	2023-12-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2023.2294938
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Article ; Online: Routine biomarker profile for the prediction of clinical phenotypes of adult-onset Still's disease using unsupervised clustering algorithm.

Gallardo-Pizarro, Antonio / Campos-Rodríguez, Valerio / Martín-Iglesias, Daniel / Ruiz-Irastorza, Guillermo

International journal of rheumatic diseases

2024 Volume 27, Issue 4, Page(s) e15143

Abstract: Aim: This study addresses the challenge of predicting the course of Adult-onset Still's disease (AoSD), a rare systemic autoinflammatory disorder of unknown origin. Precise prediction is crucial for effective clinical management, especially in the ... ...

Abstract	Aim: This study addresses the challenge of predicting the course of Adult-onset Still's disease (AoSD), a rare systemic autoinflammatory disorder of unknown origin. Precise prediction is crucial for effective clinical management, especially in the absence of specific laboratory indicators. Methods: We assessed the effectiveness of combining traditional biomarkers with the k-medoids unsupervised clustering algorithm in forecasting the various clinical courses of AoSD-monocyclic, polycyclic, or chronic articular. This approach represents an innovative strategy in predicting the disease's course. Results: The analysis led to the identification of distinct patient profiles based on accessible biomarkers. Specifically, patients with elevated ferritin levels at diagnosis were more likely to experience a monocyclic disease course, while those with lower erythrocyte sedimentation rate could present with any of the clinical courses, monocyclic, polycyclic, or chronic articular, during follow-up. Conclusion: The study demonstrates the potential of integrating traditional biomarkers with unsupervised clustering algorithms in understanding the heterogeneity of AoSD. These findings suggest new avenues for developing personalized treatment strategies, though further validation in larger, prospective studies is necessary.
MeSH term(s)	Adult ; Humans ; Prospective Studies ; Still's Disease, Adult-Onset/diagnosis ; Still's Disease, Adult-Onset/drug therapy ; Biomarkers ; Cluster Analysis ; Algorithms ; Phenotype
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-04-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2426924-4
ISSN	1756-185X ; 1756-1841
ISSN (online)	1756-185X
ISSN	1756-1841
DOI	10.1111/1756-185X.15143
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Article ; Online: What are the prospects for antiplatelet agents for thromboprophylaxis in antiphospholipid syndrome?

Ruiz-Irastorza, Guillermo / Khamashta, Munther A

Expert review of clinical immunology

2022 Volume 18, Issue 8, Page(s) 779–781

MeSH term(s)	Anticoagulants/therapeutic use ; Antiphospholipid Syndrome/drug therapy ; Humans ; Platelet Aggregation Inhibitors/therapeutic use ; Venous Thromboembolism
Chemical Substances	Anticoagulants ; Platelet Aggregation Inhibitors
Language	English
Publishing date	2022-06-19
Publishing country	England
Document type	Editorial
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2022.2090338
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Article ; Online: Letter to the editor: Gwinnutt JM, Toyoda T, Barraclough M, Verstappen SMM, Hornberger M, MacGregor A. Cognitive impairment in the immune-mediated inflammatory diseases compared with age-matched controls: Systematic review and meta-regression.

Recio-Barbero, María / Segarra, Rafael / Perez-Arbide, Emma / Ruiz-Irastorza, Guillermo

Seminars in arthritis and rheumatism

2023 Volume 62, Page(s) 152236

MeSH term(s)	Humans ; Cognitive Dysfunction ; Inflammation ; Systematic Reviews as Topic
Language	English
Publishing date	2023-07-28
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	120247-9
ISSN	1532-866X ; 0049-0172
ISSN (online)	1532-866X
ISSN	0049-0172
DOI	10.1016/j.semarthrit.2023.152236
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