scholarly journals Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 323
Author(s):  
Krzysztof Bonek ◽  
Leszek Roszkowski ◽  
Magdalena Massalska ◽  
Wlodzimierz Maslinski ◽  
Marzena Ciechomska
Keyword(s):  
Rheumatoid Arthritis ◽  
Adult Population ◽  
Disease Modifying Antirheumatic Drugs ◽  
Biologic Drugs ◽  
Dmard Therapy ◽  
Gm Csf ◽  
Proven Efficacy ◽  
Unequal Access ◽  
Spectrum Of Patients

Rheumatoid arthritis (RA) affects around 1.2% of the adult population. RA is one of the main reasons for work disability and premature retirement, thus substantially increasing social and economic burden. Biological disease-modifying antirheumatic drugs (bDMARDs) were shown to be an effective therapy especially in those rheumatoid arthritis (RA) patients, who did not adequately respond to conventional synthetic DMARD therapy. However, despite the proven efficacy, the high cost of the therapy resulted in limitation of the widespread use and unequal access to the care. The introduction of biosimilars, which are much cheaper relative to original drugs, may facilitate the achievement of the therapy by a much broader spectrum of patients. In this review we present the properties of original biologic agents based on cytokine-targeted (blockers of TNF, IL-6, IL-1, GM-CSF) and cell-targeted therapies (aimed to inhibit T cells and B cells properties) as well as biosimilars used in rheumatology. We also analyze the latest update of bDMARDs’ possible influence on DNA methylation, miRNA expression and histone modification in RA patients, what might be the important factors toward precise and personalized RA treatment. In addition, during the COVID-19 outbreak, we discuss the usage of biologicals in context of effective and safe COVID-19 treatment. Therefore, early diagnosing along with therapeutic intervention based on personalized drugs targeting disease-specific genes is still needed to relieve symptoms and to improve the quality of life of RA patients.

scholarly journals Search of Official Nationwide Database in Japan for Adverse Events Associated with Disease-modifying Antirheumatic Drug Therapies: Focus on Therapies in Combination with Methotrexate Author

2021 ◽  
Author(s):  
Shigeko Inokuma
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Lymphoproliferative Disease ◽  
The Other ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Biologic Drugs ◽  
Dmard Therapy ◽  
Disease Modifying ◽  
Line Drug

Abstract Disease-modifying antirheumatic drugs (DMARDs) are essential for rheumatoid arthritis (RA) therapy, and many synthetic and biologic drugs are available. DMARDs are frequently prescribed in combination with methotrexate (MTX), as it is the first-line drug. The adverse events (AEs) associated with DMARDs have sometimes unfavorable outcomes. Major AEs, particularly therapies in combination with methotrexate, were investigated in this study. A search of the website of the Japanese Pharmaceuticals and Medical Devices Agency for AEs associated with therapies with five DMARDs (MTX, tacrolimus, adalimumab, tocilizumab, and abatacept) reported from 2014 to 2016 was performed. The AEs searched included lymphoproliferative disease (LPD), cytopenia, interstitial pneumonia (IP), infectious pneumonia other than Pneumocystis jirovecii pneumonia (PCP) (i-Pn), and PCP. The number of cases of each AE and its ratio to the total number of cases of all AEs associated with each DMARD therapy were examined. Data were compared among AEs and DMARDs. MTX therapy in combination with other DMARDs was examined for rheumatoid arthritis (RA) cases. On the website, a total of 8874 cases were listed as having AEs associated with therapies with the five DMARDs. For MTX therapy, LPD was the most frequent (1438 cases, 36.4% of all AE cases), followed by cytopenia (10.9%), IP (6.2%), i-Pn (4.1%), and PCP (2.6%). Under therapy with any of the other four DMARDs, i-Pn showed the largest number of cases and the highest ratio (4.2–15.3%); other AEs varied in number and ratio. The proportion of use of MTX in combination with the four DMARDs was highest for PCP (67/71, 94.4%), followed by LPD (50/73, 68.5%), cytopenia (48/73, 65.8%), i-Pn (101/173, 58.4%,), and IP (36/80, 45.0%) (Table 1). In total, including cases reported for MTX therapy, 98.2% (1286/1309) of LPD cases, 88.5% (193/218) of cytopenia cases, 79.8% (174/218) of IP cases, 76.4% (233/305) of i-Pn cases, and 97.6% (165/169) of PCP cases had MTX. In conclusion, LPD was by far the most frequent AE associated with MTX therapy. PCP was strongly associated with the use of MTX in combination with another DMARD. For therapy with any of the other four DMARDs, i-Pn showed the highest ratio.

scholarly journals Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Esteban A. Gomez ◽  
Romain A. Colas ◽  
Patricia R. Souza ◽  
Rebecca Hands ◽  
Myles J. Lewis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Initiation ◽  
Plasma Concentrations ◽  
Docosapentaenoic Acid ◽  
Lipid Mediator ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Dmard Therapy ◽  
Disease Modifying ◽  
Learning Analysis

Abstract Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA.

scholarly journals Unmet Needs in the Treatment of RA in the Era of Jak-i: IDRA (Italian Delphi Rheumatoid Arthritis) Consensus

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
R. Caporali ◽  
A. Doria ◽  
G. F. Ferraccioli ◽  
P. L. Meroni ◽  
D. Zavaglia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Unmet Needs ◽  
Therapeutic Option ◽  
Adult Population ◽  
Joint Damage ◽  
Systemic Involvement ◽  
Medical Needs ◽  
Effective Therapeutic Option ◽  
General Physical

Rheumatoid arthritis is the most common autoimmune arthritis in adult population. This disease is characterized by joint damage and systemic involvement that lead to general physical and mental impairment with consequent worsening of quality of life. Rheumatoid arthritis is also associated with a large economic burden to healthcare systems. The evidence from the literature indicates that, despite available treatments, several unmet needs still interfere with rheumatoid arthritis management. Based on this evidence, some of the unmet medical needs currently present in the management of the rheumatoid arthritis were identified and a Delphi questionnaire was submitted to 60 Italian Rheumatologists. The aim of this Delphi was to achieve a broad consensus on the most relevant unmet needs identified, in order to present the Italian reality in view of the availability of new molecules that could provide an effective therapeutic option in the treatment of patients with rheumatoid arthritis.

scholarly journals Effective Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease by B-Cell Targeted Therapy with Rituximab

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Wolfgang Hartung ◽  
Judith Maier ◽  
Michael Pfeifer ◽  
Martin Fleck
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Treatment Options ◽  
Joint Inflammation ◽  
Dmard Therapy ◽  
Sustained Improvement ◽  
Minute Walk

Rheumatoid arthritis- (RA-) associated interstitial lung disease (RA-ILD) is the extra-articular complication with most adverse impact on the quality of life and survival in RA patients. However, treatment options are limited and controlled studies are lacking. Here, we present the case of a 66-year-old patient suffering from severe RA-ILD, which has been successfully treated with Rituximab (RTX). After failure of conventional DMARD therapy, our patient showed sustained improvement of clinical pulmonary parameters as well as joint inflammation following B-cell depletion with RTX. The six-minute-walk test improved from 380 meters to 536 meters and the forced vital capacity from 2.49 liters to 3.49. The disease activity score could be reduced from 7.7 to 2.8. Therefore, RTX might be considered as an alternative treatment for RA-ILD in patients not responding to conventional DMARD therapy.

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