Challenges in the treatment of Rheumatoid Arthritis

Paola Conigliaro; Paola Triggianese; Erica De Martino; Giulia Lavinia Fonti; Maria Sole Chimenti; Flavia Sunzini; Alessandra Viola; Claudia Canofari; Roberto Perricone

doi:10.1016/j.autrev.2019.05.007

Challenges in the treatment of Rheumatoid Arthritis

Autoimmun Rev. 2019 Jul;18(7):706-713. doi: 10.1016/j.autrev.2019.05.007. Epub 2019 May 3.

Authors

Paola Conigliaro¹, Paola Triggianese², Erica De Martino², Giulia Lavinia Fonti², Maria Sole Chimenti², Flavia Sunzini², Alessandra Viola², Claudia Canofari², Roberto Perricone²

Affiliations

¹ Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Italy. Electronic address: paola.conigliaro@uniroma2.it.
² Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Italy.

PMID: 31059844
DOI: 10.1016/j.autrev.2019.05.007

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.

Keywords: Comorbidities; Diet; Extra-articular manifestations; HLA; Physical activity; Pregnancy; Rheumatoid Arthritis; bDMARDs.

Publication types

Review

MeSH terms

Animals
Antirheumatic Agents / therapeutic use*
Arthritis, Rheumatoid / drug therapy*
Humans

Substances

Antirheumatic Agents