Clinical Study Evaluating the Effect of Carvedilol in Patients With Active Rheumatoid Arthritis

heumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. It is characterized with chronic production of pro-inflammatory cytokines, which lead to cartilage and bone degradation that results in tissue destruction by the patients' immune system (Guo et al., 2018). The high systemic inflammatory burden associated with RA appears to be a key driver of increased CV risk. This inflammatory state is linked to endothelial dysfunction and accelerated atherosclerosis (Giollo et al., 2018). Consequently, RA increases the risk of cardiovascular (CV) mortality by up to 50% compared with the general population and CV disease is the leading cause of death in RA patients. This leads to suggestion that reducing inflammation lowers CV risk in RA (Dijkshoorn et al., 2022). Therapies targeting inflammation remain the mainstay of RA treatment such as non- steroidal anti-inflammatory drugs (NSAIDs), non-biologic and biologic disease-modifying anti-rheumatic drugs (DMARDs), immune-osuppressants, and corticosteroids. However, current treatment strategies have many adverse effects and a significant proportion of RA patients did not effectively respond to them (Aletaha and Smolen., 2018). Consequently, it is crucial to find new therapeutic approaches for the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients. Carvedilol is a non-selective β-blocker with α-adrenergic receptor antagonism properties which has been safely used in treatment of several cardiovascular disorders (Prajapati et al., 2017). Previous animal studies highlights evidences for the promising anti- arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) and eicosanoids including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) (Arab and El-Sawalhi, 2013; Ahmed et al., 2017; Osman et al., 2017). Taken together, carvedilol has powerful antioxidant/anti-inflammatory properties; we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders