Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations: ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren's syndrome, TCR = T cell receptor.
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PMID:New pharmacological strategies in rheumatic diseases. 2797 25

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory condition that is associated with progressive joint destruction and reduced quality of life. Despite the common use of disease-modifying anti-rheumatic drugs (DMARDs) in PsA, their influence has been investigated in a number of studies with conflicting results. There is also concern about their safety and tolerability. Tofacitinib is an orally administered Janus kinase (JAK) inhibitor that has recently been approved for the treatment of PsA by various international regulatory authorities, including the FDA, EMA, and NICE. Areas covered: In this review, the mechanism of action and the pharmacokinetic properties of tofacitinib are discussed. The data from two large phase III clinical studies evaluating the use of tofacitinib in PsA is also discussed in addition to the findings from other relevant studies. Expert opinion: The clinical data demonstrate significant improvement in disease activity in PsA patients using tofacitinib. There is also an acceptable clinical safety profile for the drug. Tofacitinib has various advantages over several existing drug treatments for PsA including an oral route of administration, a short half-life and a fast onset of action. Consequently, we anticipate that tofacitinib will become an increasingly used targeted synthetic DMARD (tsDMARD) for active PsA over the coming years.
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PMID:An evaluation of tofacitinib for the treatment of psoriatic arthritis. 3145 40

Three Janus kinase (JAK) inhibitors, ruxolitinib, tofacitinib, and baricitinib, are currently approved by the FDA/EMA for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative rectocolitis. The inhibition of JAK/STAT signaling by these small molecules, downstream of several cytokine receptors, results in lower pro-inflammatory gene expression. Given the cytokine profiles observed in rheumatologic diseases, most of the recent therapeutic strategies target cytokines, either directly or through their receptors. Each cytokine receptor recruits a specific combination of JAKs to activate different programs in cells. The approved drugs are panJAK inhibitors, able to impede more than one pathway. These drugs are being tested in various rheumatologic disorders. At the same time, more specific molecules able to target one specific JAK are being developed. In this review, we describe the expanding spectrum of rheumatologic and autoimmune conditions for which JAK inhibition may represent new avenues in clinical practice.
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PMID:Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum. 3152 93

Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-23, mainly produced by dendritic cells, maintains the differentiation of naive T cells to Th17 cells, the keystone effector cells in psoriasis. The clinical effectiveness of therapeutic agents targeting this cytokine has been demonstrated in moderate-to-severe plaque psoriasis. Guselkumab is the first human antibody against the p40 subunit of the IL-23 receptor approved by the US FDA and the EMA for this indication in adult patients (2017). It has also been approved for treatment of psoriatic arthritis in Japan (April 2018). This article reviews the published data relating to the efficacy and safety of guselkumab for treatment of moderate-to-severe plaque psoriasis.
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PMID:Guselkumab in the treatment of moderate-to-severe plaque psoriasis. 3231 22

Psoriatic arthritis (PsA) is a heterogeneous chronic rheumatic disorder with numerous phenotypic facets. A better in deep understanding of the pathophysiologic mechanisms leading to psoriasis and PsA has contributed to the introduction of novel therapeutic agents. IL-17 is at the heart and a critical factor in the onset of PsA. Ixekizumab, a high-affinity monoclonal antibody against IL-17 A, has been approved by the US FDA in March 2016 for baseline psoriasis and Dec 2017 for PsA; by the EMA in April 2016 and January 2018, respectively. This article reviews the published data relating to ixekizumab efficacy and safety in the PsA treatment.
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PMID:Ixekizumab in the treatment of psoriatic arthritis. 3316 45