The effects and side effects of laquinimod for the treatment of multiple sclerosis patients: a systematic review and meta-analysis of clinical trials

Rouhi, Faeze; Mohammadpour, Zinat; Noureini, Sakineh Kazemi; Abbastabar, Hedayat; Harirchian, Mohammad Hossein; Bitarafan, Sama

doi:10.1007/s00228-019-02827-6

Cited by 6 publications

(5 citation statements)

References 30 publications

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“…Phase II/III clinical trials indicate therapeutic efficacy of LAQ in patients with multiple sclerosis [45,46], as also confirmed in recent metaanalysis [47]. Herein, a significantly higher risk of LAQ treatment was associated with back pain, headache, and vomiting [47]. Tasquinimod is intended for the oral treatment of prostate cancer, but also comes with adverse events (e.g., skeletal pain, digestive disorders, insomnia) [48,49].…”

Section: Discussionmentioning

confidence: 82%

“…Thereafter, LAQ and TASQ were developed and intended as safer derivatives [43,44]. Phase II/III clinical trials indicate therapeutic efficacy of LAQ in patients with multiple sclerosis [45,46], as also confirmed in recent metaanalysis [47]. Herein, a significantly higher risk of LAQ treatment was associated with back pain, headache, and vomiting [47].…”

Section: Discussionmentioning

confidence: 83%

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Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins

Rikken

Brink

Vlijmen-Willems

et al. 2022

IJMS

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Atopic dermatitis (AD) is a common T-helper 2 (Th2) lymphocyte-mediated chronic inflammatory skin disease characterized by disturbed epidermal differentiation (e.g., filaggrin (FLG) expression) and diminished skin barrier function. Therapeutics targeting the aryl hydrocarbon receptor (AHR), such as coal tar and tapinarof, are effective in AD, yet new receptor ligands with improved potency or bioavailability are in demand to expand the AHR-targeting therapeutic arsenal. We found that carboxamide derivatives from laquinimod, tasquinimod, and roquinimex can activate AHR signaling at low nanomolar concentrations. Tasquinimod derivative (IMA-06504) and its prodrug (IMA-07101) provided full agonist activity and were most effective to induce FLG and other epidermal differentiation proteins, and counteracted IL-4 mediated repression of terminal differentiation. Partial agonist activity by other derivatives was less efficacious. The previously reported beneficial safety profile of these novel small molecules, and the herein reported therapeutic potential of specific carboxamide derivatives, provides a solid rationale for further preclinical assertation.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 83%

Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins

Rikken

Brink

Vlijmen-Willems

et al. 2022

IJMS

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“…These effects were explained by the ability of laquinimod to inhibit NF-kB pathway (331). The migration of macrophages, CD4+, and CD8+ T cells into the CNS was shown to be reduced by laquinimod, by downregulation of the VLA-4 mediated lymphocytes adhesiveness (332). Additionally, decreased axonal damage, synaptic loss, and inflammatory demyelination have been reported in laquinimod' treated MS (333).…”

Section: Immune-modulating Agentsmentioning

confidence: 94%

Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

Liu

Zhao

et al. 2022

Front. Immunol.

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron’s axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown. However, immune mechanisms, especially those linked to the aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 and Th17 populations of lymphocytes were primarily associated with MS pathogenesis. These lymphocytes are essential for differentiation of encephalitogenic CD8+ T cell and Th17 lymphocyte crossing the blood brain barrier and targeting myelin sheath in the CNS. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies. In later studies, aberrant function of Treg and Th9 cells was identified as contributing to MS. This review summarizes the aberrant function and count of lymphocyte, and the contributions of these cell to the mechanisms of MS. Additionally, we have outlined the novel MS therapeutics aimed to amend the aberrant function or counts of these lymphocytes.

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“…Migraine MS patients were more symptomatic as compared to MS patients without migraine. In approximately 2/3 rd of the patients' headaches precedes onset of MS symptoms and 80% of MS patients reported headaches after onset of treatment (23,35,(46)(47)(48).…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 99%

“…PA is a relatively rare chronic inflammatory disease with psoriasis. Psoriasis affects 0-8.5% of the population in the world and approximately 0.91% individuals in the U.S. and arthritis in these patients accounts for only 6% of the cases making it relatively rare condition (48,52). PA symptoms includes pain in joints, reduced joint movements, skin rashes and pain in ligaments & tendons.…”

Section: Psoriatic Arthritis (Pa)mentioning

confidence: 99%

Orofacial pain considerations in autoimmune disorders: narrative review

Singh¹,

George²,

Kalladka³

et al. 2024

Front Oral Maxillofac Med

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Immunity is an essential self-defensive mechanism comprised of biological structures and processes within an organism that protects it against invasive microorganism, viruses, malignancies and diseases (1,2). Malfunction of the immune system can cause the self-destruction of its own cells, tissues, and organs resulting in autoimmune diseases (AD) (2). Approximately, 5% of the population worldwide and 3% of US population suffer from AD imposing a significant burden of morbidity and mortality (1,3).Scientific research and literatures have provided substantial advancements in our understanding of human autoimmunity that have led to improvements in classification, diagnosis and management of the diseases (1-3). Tissue damage in AD is an exaggerated responses of the immune system towards self-antigens (1). Evidence suggests that antigens released by bacteria, viruses, toxins, blood, and tissue can trigger an

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The effects and side effects of laquinimod for the treatment of multiple sclerosis patients: a systematic review and meta-analysis of clinical trials

Cited by 6 publications

References 30 publications

Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins

Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins

Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

Orofacial pain considerations in autoimmune disorders: narrative review

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