An Insight on the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Ali, Murtaza; Firoz, Chelapram K.; Jabir, Nasimudeen R.; Rehan, Mohd; Khan, Mohd Shahnawaz; Tabrez, Shams

doi:10.2174/1871530318666171207145003

Cited by 8 publications

(7 citation statements)

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“…Systemic lupus erythematosus (SLE), an autoimmune disease that primarily affects women of childbearing age, is characterized by immunologic abnormalities and multisystem involvement. Autoantibody formation can lead to immune complex deposition, thought to be one mechanism leading to tissue damage (1). While the disease is heterogeneous in its clinical presentation, course, and prognosis, predominant manifestations are arthritis, rash, oral or nasal ulcers, Raynaud’s phenomenon, and/or severe fatigue.…”

Section: Introductionmentioning

confidence: 99%

“…Glucocorticoids, antimalarials, and off-label use of immunosuppressive drugs, such as azathioprine and mycophenolate, are the mainstay of SLE treatment. However, because of their toxicities and suboptimal efficacy, a significant unmet need exists for safer and more effective therapy (1). Only one targeted agent, belimumab, has been approved for the treatment of SLE in the past 60 years (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy, Safety, and Pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor Fenebrutinib (GDC‐0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial

Isenberg

Furie

Jones³

et al. 2021

Arthritis & Rheumatology

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Objective Fenebrutinib (GDC‐0853) is a noncovalent, oral, and highly selective inhibitor of Bruton’s tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo‐controlled study. Methods Patients who had moderately to severely active SLE while receiving background standard therapy were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily. Glucocorticoid taper was recommended from weeks 0 to 12 and from weeks 24 to 36. The primary end point was the SLE Responder Index 4 (SRI‐4) response at week 48. Results Patients (n = 260) were enrolled from 44 sites in 12 countries, with the majority from Latin America, the US, and Western Europe. The SRI‐4 response rates at week 48 were 51% for fenebrutinib 150 mg once daily (P = 0.37 versus placebo), 52% for fenebrutinib 200 mg twice daily (P = 0.34 versus placebo), and 44% for placebo. British Isles Lupus Assessment Group–based Combined Lupus Assessment response rates at week 48 were 53% for fenebrutinib 150 mg once daily (P = 0.086 versus placebo), 42% for fenebrutinib 200 mg twice daily (P = 0.879 versus placebo), and 41% for placebo. Safety results were similar across all arms, although serious adverse events were more frequent with fenebrutinib 200 mg twice daily. By week 48, patients treated with fenebrutinib had reduced levels of a BTK‐dependent plasmablast RNA signature, anti–double‐stranded DNA autoantibodies, total IgG, and IgM, as well as increased complement C4 levels, all relative to placebo. Conclusion While fenebrutinib had an acceptable safety profile, the primary end point, SRI‐4 response, was not met despite evidence of strong pathway inhibition.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor Fenebrutinib (GDC‐0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial

Isenberg

Furie

Jones³

et al. 2021

Arthritis & Rheumatology

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“…Systemic lupus erythematosus (SLE), an autoimmune disease, is characterized by abnormal inflammatory responses due to complex, aberrant humoral and cellular immune responses. The pathogenesis of SLE is largely unknown; however, data from the literature suggest that manifestation of this disease is the result of several environmental, hormonal, and nutritional factors that, in predisposed subjects, contribute to impaired cellular, and humoral immune responses (1)(2)(3). Accordingly, the presence of autoantibodies is nearly universal among patients with SLE.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

et al. 2020

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.

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“…Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody formation, immune complex deposition, multisystem involvement, and tissue damage [ 110 ]. Several components of BTK signaling pathways are altered in B cells from patients with SLE, and BTKis are promising for the treatment of SLE.…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Bruton’s Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives

Robak

2022

JCM

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The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the management of patients with B-cell lymphoid malignancies. BTK is an important molecule that interconnects B-cell antigen receptor (BCR) signaling. BTK inhibitors (BTKis) are classified into three categories, namely covalent irreversible inhibitors, covalent reversible inhibitors, and non-covalent reversible inhibitors. Ibrutinib is the first covalent, irreversible BTK inhibitor approved in 2013 as a breakthrough therapy for chronic lymphocytic leukemia patients. Subsequently, two other covalent, irreversible, second-generation BTKis, acalabrutinib and zanubrutinib, have been developed for lymphoid malignancies to reduce the ibrutinib-mediated adverse effects. More recently, irreversible and reversible BTKis have been under development for immune-mediated diseases, including autoimmune hemolytic anemia, immune thrombocytopenia, multiple sclerosis, pemphigus vulgaris, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, and chronic spontaneous urticaria, among others. This review article summarizes the preclinical and clinical evidence supporting the role of BTKis in various autoimmune, allergic, and inflammatory conditions.

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An Insight on the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Abstract: The present review highlights the various causatives of SLE, particularly the genetic alteration in B- and T-cell-related proteins. We have also delineated some of the available therapeutic strategies for the treatment of SLE.

Cited by 8 publications

References 0 publications

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor Fenebrutinib (GDC‐0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor Fenebrutinib (GDC‐0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

Bruton’s Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives

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