Challenges in the treatment of Rheumatoid Arthritis

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.

Detection and Comparative Analysis of Methylomic Biomarkers of Rheumatoid Arthritis

“…Another RA-associated gene HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) was also a methylation biomarker (cg27107292) detected in this study (Conigliaro et al, 2019;Okada et al, 2019). HLA-DRB1 was one of the first few RA biomarkers discovered four decades ago and harbored more than 100 RA-associated loci (Okada et al, 2019).…”

COVID-19 infection and rheumatoid arthritis: Faraway, so close!

“…The COVID-19 epidemic represents a health emergency that is inevitably affecting the management of a complex disease such as RA [115,116]. As a chronic autoimmune inflammatory disorder, RA carries a higher infectious risk than the general population.…”

Efficacy and safety of peficitinib in rheumatoid arthritis

“…Switching from a JAK inhibitor to another one is a different matter. Unmet needs still exist as some patients fail to achieve or maintain clinical remission with biologic agents or JAK inhibitors [26]. If patients fail to respond to a biologic agent, several reports from registry data and observational studies as well as a randomized controlled trial, have suggested that switching to a drug with a different mode of action may improve efficacy, rather than switching to a second drug with a similar mode of action [27][28][29][30].…”