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Challenges in the treatment of Rheumatoid Arthritis
Paola Conigliaro1, Paola Triggianese1, Erica De Martino1
1Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Italy.
Abstract:
Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by a heterogeneous clinical response to the different treatments. Some patients are difficult to treat and do not reach the treatment targets as clinical remission or low disease activity. Known negative prognostic factors, such as the presence of auto-antiantibodies and joint erosion, the presence of a genetic profile, comorbidities and extra-articular manifestations, pregnancy or a pregnancy wish may concur to the treatment failure. In this review we aimed at identify difficult to treat RA patients and define the optimal therapeutic and environmental targets. Genetic markers of severity such as HLA-DRB1, TRAF1, PSORS1C1 and microRNA 146a are differently associated with joint damage; other gene polymorphisms seem to be associated with response to biologic disease modifying anti-rheumatic drugs (bDMARDs). The presence of comorbidities and/or extra-articular manifestations may influence the therapeutic choice; overweight and obese patients are less responsive to TNF inhibitors. In this context the patient profiling can improve the clinical outcome. Targeting different pathways, molecules, and cells involved in the pathogenesis of RA may in part justify the lack response of some patients. An overview of the future therapeutic targets, including bDMARDs (inhibitors of IL-6, GM-CSF, matrix metalloproteinases, chemokines) and targeted synthetic DMARDs (filgotinib, ABT-494, pefacitinib, decernotinib), and environmental targets is addressed. Environmental factors, such as diet and cigarette smoke, may influence susceptibility to autoimmune diseases and interfere with inflammatory pathways. Mediterranean diet, low salt intake, cocoa, curcumin, and physical activity seem to show beneficial effects, however studies of dose finding, safety and efficacy in RA need to be performed.
Insights
Identifying difficult-to-treat Rheumatoid Arthritis (RA) patients involves considering genetic factors, comorbidities, and lifestyle. Optimizing treatment requires personalized strategies and exploring novel therapeutic and environmental targets for better outcomes.
Area of Science:
- Rheumatology
- Immunology
- Genetics
Background:
- Rheumatoid Arthritis (RA) presents heterogeneous clinical responses to treatments, with some patients failing to achieve remission.
- Negative prognostic factors include auto-antibodies, joint erosion, genetic profiles, comorbidities, and extra-articular manifestations.
- Treatment failure in RA can be influenced by a complex interplay of patient-specific and external factors.
Purpose of the Study:
- To identify patients with difficult-to-treat Rheumatoid Arthritis (RA).
- To define optimal therapeutic and environmental targets for managing RA.
- To explore factors contributing to treatment resistance in RA patients.
Main Methods:
- Review of genetic markers associated with RA severity and treatment response, including HLA-DRB1, TRAF1, PSORS1C1, and microRNA 146a.
- Analysis of the impact of comorbidities, extra-articular manifestations, and patient profiling on therapeutic choices.
- Examination of future therapeutic targets, encompassing biologic and targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs and tsDMARDs).
- Evaluation of environmental factors like diet and lifestyle modifications.
Main Results:
- Genetic polymorphisms are linked to joint damage and response to biologic disease-modifying anti-rheumatic drugs (bDMARDs).
- Comorbidities and patient characteristics (e.g., obesity) affect treatment efficacy, particularly with TNF inhibitors.
- Novel therapeutic targets include inhibitors of IL-6, GM-CSF, and specific tsDMARDs like filgotinib.
- Environmental factors such as Mediterranean diet, low salt intake, cocoa, curcumin, and physical activity show potential benefits.
Conclusions:
- Personalized patient profiling is crucial for improving clinical outcomes in RA.
- Future RA management should integrate novel therapeutic strategies and environmental modifications.
- Further research is needed to establish optimal dosing, safety, and efficacy of environmental interventions in RA.
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