Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases

Morel, Nathalie; Bonjour, Maxime; Guern, Véronique Le; Jeunne, Claire Le; Mouthon, Luc; Pietté, J.C.; Costédoat-Chalumeau, Nathalie

doi:10.1177/0961203315593169

Cited by 29 publications

(14 citation statements)

References 27 publications

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“…Inflammation parameters (ESR and CRP) are generally altered in the SLE during few conditions like infection or serositis (Ryu et al, 2017). In addition, this manifestation responds promptly to colchicine, a treatment generally used in diseases considered “inflammasome guided” as the FMF (Morel et al, 2015; Padeh and Berkun, 2016). The primary molecular target of colchicine is β-tubulin inducing microtubule de-polymerization.…”

Section: Discussionmentioning

confidence: 99%

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

et al. 2019

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Introduction: P2X7R is an extracellular ATP-gated receptor involved in inflammatory and autoimmune processes mainly acting through NLPR3-inflammasome activation and IL-1β release, also implicated in lymphocyte proliferation and cellular apoptosis. Several observations from animal models and patients’ studies highlight a possible link between P2X7R-NLRP3 axis and Systemic Lupus Erythematosus (SLE) pathogenesis. The P2X7R-inflammasome axis in addition to the direct production of IL-1β and IL-18, indirectly mediates the release of other cytokines implicated in the pathogenesis of SLE, such as IL-6. The aim of this study was to investigate the role of P2X7R and NLRP3-inflammasome in SLE. Methods: Forty-eight SLE patients, 16 with (SLE-S) and 32 without (SLE-NS) history of serositis, and 20 healthy control (HC) subjects were enrolled. Demographic, clinical, and therapeutic data were collected. IL-1β and IL-6 plasma levels were evaluated by ELISA. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by Ficoll gradient sedimentation and employed as follows: (1) evaluation of P2X7R and NLRP3 expression by RT-PCR; (2) determination of P2X7R activity as Benzoyl ATP (BzATP)-induced [Ca 2+ ] i increments using Fura-2-AM fluorescent probe; (3) isolation of monocytes/macrophages and assessment of in vitro IL-1β and IL-6 release following stimulation with lipopolysaccharide (LPS) and BzATP, either separately or in combination. Results: Plasma IL-1β levels were unmodified in SLE respect to HC whereas IL-6 levels were higher in SLE than in HC, resulting significantly increased in SLE-S. Macrophages isolated from SLE patients released lower quantities of IL-1β after stimulation with BzATP, whereas IL-6 release was significantly augmented in SLE-NS respect to both HC and SLE-S after all types of stimulation. The [Ca 2+ ]i increase following BzATP stimulation was significantly lower in PBMCs from SLE patients than in PBMCs from HC. RT-PCR showed significantly reduced P2X7R and significantly augmented NLRP3 expression in PBMCs from SLE patients. Conclusion: Our data indicate reduced P2X7R expression and function in SLE patients compared with HC and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis.

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Section: Discussionmentioning

confidence: 99%

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

et al. 2019

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“…Colchicine is a microtubule inhibitor drug widely used in the management of gout and conditions that involve localized inflammation including serositis e.g., Behcet's disease, Systemic Lupus Erythematosus (SLE), and pericarditis (35,36).…”

Section: Inflammasomementioning

confidence: 99%

Immunomodulatory Drugs in the Management of SARS-CoV-2

2020

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With the onset of the global pandemic in 2020 of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), there has been increasing research activity around certain disease-modifying drugs that are used for the management of inflammatory disorders such as rheumatoid arthritis, spondyloarthrosis, psoriatic arthritis, systemic lupus erythematosus, and inflammatory bowel disease for managing coronavirus symptoms. In the conditions mentioned, many people are on long-term treatment with agents including hydroxychloroquine, tumor necrosis factor alpha (TNFα) inhibitor drugs, other biologic agents such as monoclonal antibodies to IL-6 and Janus kinase inhibitors including baricitinib and tofacitinib, which are used to control inflammatory responses in their respective auto-immune condition. There is emerging data that immunomodulatory drugs could be protective at reducing certain features of SARS-CoV-2 and improving recovery. In addition, it is important to understand if subjects being treated with the immunomodulatory agents described have a less severe SARS-CoV-2 infection, as they are deemed some protection from their immunomodulatory treatment, or if they develop infections similar to non-immunocompromised patients. There is a huge unmet clinical need to advise patients responsibly about whether they should remain on their immunomodulatory treatment or not in light of Covid-19 infection. In this article we will discuss potential treatment options for SARS-CoV-2 using immunomodulatory drugs and at what stage of the condition they may be beneficial. Viable treatment options during the global coronavirus pandemic are a much-needed and an intensely active area of research.

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“…Colchicine is currently used to treat various inflammatory conditions, including gout, FMF, Behcet's disease, and recurrent pericarditis. Pericarditis associated with lupus has traditionally been treated with corticosteroids, although colchicine demonstrated effectiveness and was well tolerated in a series of 10 cases of lupus with pericarditis [58]. Colchicine has also exhibited long-term safety in studies of children with FMF with minimal adverse effects.…”

Section: Statins and The Apple Trialmentioning

confidence: 99%

The potential role of Colchicine in preventing coronary vascular disease in childhood‐onset lupus: a new view on an old drug

2021

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Background Patients with systemic lupus erythematous have a significantly increased risk of cardiovascular disease, which is not fully explained by traditional cardiovascular disease risk factors. Despite increasing life expectancy in patients with systemic lupus erythematous, mortality due to cardiovascular disease, the major cause of death in these patients, has not changed. Children with lupus suffer from more aggressive disease compared to their adult counterparts, and there is a growing concern for their increased risk of cardiovascular disease as they age. Body: There is an unmet need for therapies to address the increased risk of cardiovascular disease in childhood-onset lupus. Colchicine has many anti-inflammatory and cardiovascular protective properties, including inhibition of IL-1β and IL-18 activity, key proinflammatory cytokines that are predictive of future adverse cardiovascular events. In the Colchicine Cardiovascular Outcomes Trial (COLCOT), colchicine was recently found to have significant benefit with minimal risk in adults with previous myocardial infarction for prevention of secondary vascular disease. While adult studies are promising, no studies have been conducted in pediatric patients to investigate colchicine’s potential for cardiovascular protection in children and adolescents with lupus. Conclusions Studies investigating colchicine’s potential role for cardiovascular protection are needed in pediatric patients with systemic lupus erythematous.

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Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases

Abstract: Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up.

Cited by 29 publications

References 27 publications

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

Immunomodulatory Drugs in the Management of SARS-CoV-2

The potential role of Colchicine in preventing coronary vascular disease in childhood‐onset lupus: a new view on an old drug

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