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  1. Article ; Online: Outlook of the jakinibs in systemic lupus erythematous after baricitinib failed.

    Mok, Chi Chiu

    International journal of rheumatic diseases

    2024  Volume 27, Issue 2, Page(s) e15082

    MeSH term(s) Humans ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/drug therapy ; Azetidines/adverse effects ; Sulfonamides/adverse effects ; Purines/adverse effects ; Pyrazoles
    Chemical Substances baricitinib (ISP4442I3Y) ; Azetidines ; Sulfonamides ; Purines ; Pyrazoles
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Editorial
    ZDB-ID 2426924-4
    ISSN 1756-185X ; 1756-1841
    ISSN (online) 1756-185X
    ISSN 1756-1841
    DOI 10.1111/1756-185X.15082
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  2. Article: Prognostic Stratification of Lupus Nephritis: The Importance of Renal Histology.

    Mok, Chi Chiu

    The Journal of rheumatology

    2023  Volume 50, Issue 9, Page(s) 1095–1096

    MeSH term(s) Humans ; Lupus Nephritis/pathology ; Prognosis ; Kidney/pathology ; Kidney Failure, Chronic ; Retrospective Studies
    Language English
    Publishing date 2023-06-01
    Publishing country Canada
    Document type Editorial ; Comment
    ZDB-ID 194928-7
    ISSN 1499-2752 ; 0315-162X
    ISSN (online) 1499-2752
    ISSN 0315-162X
    DOI 10.3899/jrheum.2023-0381
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  3. Article ; Online: Combination strategies for lupus nephritis: facts and controversies.

    Mok, Chi Chiu

    Expert review of clinical immunology

    2023  Volume 19, Issue 5, Page(s) 527–536

    Abstract: Introduction: There is an unmet need to improve the efficacy of therapeutic regimens in lupus nephritis (LN). Cocktail immunosuppressive therapy for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, ... ...

    Abstract Introduction: There is an unmet need to improve the efficacy of therapeutic regimens in lupus nephritis (LN). Cocktail immunosuppressive therapy for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, the potential increase in the risk of serious and opportunistic infections is a concern. Moreover, the timing of combination therapy, adoption of a step-up or step-down approach, and the choice of drugs is still controversial, partly related to the cost-effectiveness issue.
    Areas covered: Evidence of a combination of conventional, newer immunosuppressive, and biologic/targeted agents in LN.
    Expert opinion: Early combination of conventional regimens with anti-B cell activation factor (anti-BAFF) or calcineurin inhibitors (CNIs) enhances the therapeutic effect without increasing serious adverse events in LN. However, combining anti-CD20 and anti-BAFF biologics appears to be less promising from the results of clinical trials. Initial combination strategy may be more cost-effective for patients at risk of treatment failure and renal function deterioration. With the availability of more options, the treat-to-target approach in LN is increasingly feasible and further studies are needed to compare the step-up and step-down approaches in the treatment of LN.
    MeSH term(s) Humans ; Lupus Nephritis/drug therapy ; Immunosuppressive Agents/therapeutic use ; Calcineurin Inhibitors/therapeutic use ; Immunosuppression Therapy ; Antibodies/therapeutic use ; Lupus Erythematosus, Systemic/drug therapy
    Chemical Substances Immunosuppressive Agents ; Calcineurin Inhibitors ; Antibodies
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2274260-8
    ISSN 1744-8409 ; 1744-666X
    ISSN (online) 1744-8409
    ISSN 1744-666X
    DOI 10.1080/1744666X.2023.2192927
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  4. Article ; Online: Targeted Small Molecules for Systemic Lupus Erythematosus: Drugs in the Pipeline.

    Mok, Chi Chiu

    Drugs

    2023  Volume 83, Issue 6, Page(s) 479–496

    Abstract: Despite the uncertainty of the pathogenesis of systemic lupus erythematosus, novel small molecules targeting specific intracellular mechanisms of immune cells are being developed to reverse the pathophysiological processes. These targeted molecules have ... ...

    Abstract Despite the uncertainty of the pathogenesis of systemic lupus erythematosus, novel small molecules targeting specific intracellular mechanisms of immune cells are being developed to reverse the pathophysiological processes. These targeted molecules have the advantages of convenient administration, lower production costs, and the lack of immunogenicity. The Janus kinases, Bruton's tyrosine kinases, and spleen tyrosine kinases are important enzymes for activating downstream signals from various receptors on immune cells that include cytokines, growth factor, hormones, Fc, CD40, and B-cell receptors. Suppression of these kinases impairs cellular activation, differentiation, and survival, leading to diminished cytokine actions and autoantibody secretion. Intracellular protein degradation by immunoproteasomes, levered by the cereblon E3 ubiquitin ligase complex, is an essential process for the regulation of cellular functions and survival. Modulation of the immunoproteasomes and cereblon leads to depletion of long-lived plasma cells, reduced plasmablast differentiation, and production of autoantibodies and interferon-α. The sphingosine 1-phosphate/sphingosine 1-phosphate receptor-1 pathway is responsible for lymphocyte trafficking, regulatory T-cell/Th17 cell homeostasis, and vascular permeability. Sphingosine 1-phosphate receptor-1 modulators limit the trafficking of autoreactive lymphocytes across the blood-brain barrier, increase regulatory T-cell function, and decrease production of autoantibodies and type I interferons. This article summarizes the development of these targeted small molecules in the treatment of systemic lupus erythematosus, and the future prospect for precision medicine.
    MeSH term(s) Humans ; Pharmaceutical Preparations/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism ; B-Lymphocytes/metabolism ; Lupus Erythematosus, Systemic/drug therapy ; Autoantibodies ; Cytokines/metabolism ; Tyrosine
    Chemical Substances Pharmaceutical Preparations ; Sphingosine-1-Phosphate Receptors ; Autoantibodies ; Cytokines ; Tyrosine (42HK56048U)
    Language English
    Publishing date 2023-03-27
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 120316-2
    ISSN 1179-1950 ; 0012-6667
    ISSN (online) 1179-1950
    ISSN 0012-6667
    DOI 10.1007/s40265-023-01856-x
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  5. Article ; Online: A new old treatment for lupus nephritis.

    Mok, Chi Chiu

    Lancet (London, England)

    2021  Volume 397, Issue 10289, Page(s) 2027–2029

    MeSH term(s) Humans ; Immunosuppressive Agents/therapeutic use ; Lupus Nephritis/drug therapy
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2021-05-07
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(21)00663-2
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  6. Article ; Online: De novo lupus nephritis after SARS-CoV-2 infection.

    Mok, Chi Chiu / Chu, Chiu Sum / Tse, Sau Mei

    Lupus

    2023  Volume 32, Issue 7, Page(s) 893–899

    Abstract: The relationship between viral infection and onset of autoimmune diseases such as systemic lupus erythematosus remains uncertain. During the COVID-19 pandemic, organ-specific and multisystemic autoimmune phenomena temporally related to the viral ... ...

    Abstract The relationship between viral infection and onset of autoimmune diseases such as systemic lupus erythematosus remains uncertain. During the COVID-19 pandemic, organ-specific and multisystemic autoimmune phenomena temporally related to the viral infection have been described. Immune dysregulation triggered by the SARS-CoV-2 virus leading to hyperactivation of both the innate and adaptive immune systems contributes to the excessive production of pro-inflammatory cytokines, autoantibodies, and subsequent autoimmune manifestations. We report two patients without known autoimmune diseases who developed lupus nephritis shortly after a documented mild SARS-CoV-2 infection. Together with other similar cases in the literature, the observation supports a viral trigger of the development of systemic lupus erythematosus in susceptible individuals.
    MeSH term(s) Humans ; Lupus Nephritis/etiology ; Lupus Erythematosus, Systemic ; COVID-19/complications ; Pandemics ; SARS-CoV-2 ; Autoimmune Diseases
    Language English
    Publishing date 2023-05-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 1154407-7
    ISSN 1477-0962 ; 0961-2033
    ISSN (online) 1477-0962
    ISSN 0961-2033
    DOI 10.1177/09612033231175280
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  7. Article ; Online: Response to: 'Correspondence on 'Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis'' by Xu.

    Mok, Chi Chiu

    Annals of the rheumatic diseases

    2020  Volume 81, Issue 12, Page(s) e247

    MeSH term(s) Humans ; Mycophenolic Acid/therapeutic use ; Tacrolimus/therapeutic use ; Lupus Nephritis/drug therapy ; Induction Chemotherapy ; Immunosuppressive Agents/therapeutic use ; Immunosuppressive Agents/pharmacology ; Remission Induction ; Cyclophosphamide/therapeutic use ; Treatment Outcome
    Chemical Substances Mycophenolic Acid (HU9DX48N0T) ; Tacrolimus (WM0HAQ4WNM) ; Immunosuppressive Agents ; Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2020-10-06
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article ; Comment
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/annrheumdis-2020-219087
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  8. Article ; Online: The Dawn of a New Era of Therapies in Systemic Lupus Erythematosus.

    Mok, Chi Chiu

    Rheumatology and immunology research

    2020  Volume 1, Issue 1, Page(s) 31–37

    Abstract: Systemic lupus erythematosus (SLE) is a complicated multisystem autoimmune disease that is associated with significant mortality and morbidity in the younger population. The development of novel therapies of SLE lag behinds other autoimmune inflammatory ... ...

    Abstract Systemic lupus erythematosus (SLE) is a complicated multisystem autoimmune disease that is associated with significant mortality and morbidity in the younger population. The development of novel therapies of SLE lag behinds other autoimmune inflammatory rheumatic diseases because of its clinical and immunological heterogeneities, the complexity of outcome assessments in multiple systems, and difficulty in optimizing the design of clinical trials. Despite the futility of quite a number of clinical trials, we are seeing the dawn of novel therapeutics in SLE, given the promising results of the newer-generation anti-CD20, anti-CD40L biologics, and calcineurin inhibitors (CNIs), as well as anti-cytokine biologics, Jakinibs, and the mammalian target of rapamycin (mTOR) inhibitors. The initial success of the Jakinibs and combination regimens in SLE illustrates the importance of targeting multiple pathogenetic mechanisms. The results of the ongoing phase III clinical trials in SLE are eagerly awaited.
    Language English
    Publishing date 2020-12-01
    Publishing country Germany
    Document type Journal Article
    ISSN 2719-4523
    ISSN (online) 2719-4523
    DOI 10.2478/rir-2020-0005
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  9. Article ; Online: Systemic lupus erythematosus.

    Hoi, Alberta / Igel, Talia / Mok, Chi Chiu / Arnaud, Laurent

    Lancet (London, England)

    2024  

    Abstract: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and ... ...

    Abstract Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and kidneys. Despite substantial advances in the diagnosis and management of SLE, the burden of disease remains high. It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients. In most patients, constitutional, mucocutaneous, and musculoskeletal symptoms represent the earliest complaints; these symptoms can include fatigue, lupus-specific rash, mouth ulcers, alopecia, joint pain, and myalgia. In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria, which include a systematic evaluation of clinical manifestations (weighted within each domain) and autoantibody profiles (such as anti-double-stranded DNA, anti-Sm, hypocomplementaemia, or antiphospholipid antibodies). Non-pharmacotherapy management is tailored to the individual, with specific lifestyle interventions and patient education to improve quality of life and medication (such as hydroxychloroquine or immunosuppressant) adherence. In the last decade, there have been a few major breakthroughs in approved treatments for SLE and lupus nephritis, such as belimumab, anifrolumab, and voclosporin. However the disease course remains variable and mortality unacceptably high. Access to these expensive medications has also been restricted across different regions of the world. Nonetheless, understanding of treatment goals and strategies has improved. We recognise that the main goal of treatment is the achievement of remission or low disease activity. Comorbidities due to both disease activity and treatment adverse effects, especially infections, osteoporosis, and cardiovascular disease, necessitate vigilant prevention and management strategies. Tailoring treatment options to achieve remission, while balancing treatment-related comorbidities, are priority areas of SLE management.
    Language English
    Publishing date 2024-04-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(24)00398-2
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  10. Article ; Online: Metabolic syndrome and systemic lupus erythematosus: the connection.

    Mok, Chi Chiu

    Expert review of clinical immunology

    2019  Volume 15, Issue 7, Page(s) 765–775

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Adiponectin/immunology ; Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/immunology ; Atherosclerosis/pathology ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Inflammation/pathology ; Leptin/immunology ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Metabolic Syndrome/drug therapy ; Metabolic Syndrome/immunology ; Metabolic Syndrome/pathology ; Risk Factors
    Chemical Substances ADIPOQ protein, human ; Adiponectin ; LEP protein, human ; Leptin
    Language English
    Publishing date 2019-05-27
    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.2019.1620601
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