Anti-TNFα Biologics in the Pharmacotherapy of Rheumatoid Arthritis: Effectiveness and Safety of Infliximab, Adalimumab and Etanercept

Abstract

Introduction Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease of unknown etiology. It characteristically presents with joint inflammation that leads to joint damage, loss of function and ultimately disability. 1-3 Moreover, RA affects approximately 1% of the global adult population, occurring in 20-50 cases per 100 000 annually, 4,5 incidence being two to three times common in women than in men. 6,7 Nevertheless, though RA primarily occurs in the joints, it involves extra articular manifestations and systemic comorbidities. Substantial individual and socioeconomic burden resulting from musculoskeletal defects, reduced quality of life, declined work capacity and increased medical costs remain serious concerns. 8-10 Furthermore, though recent advances have contributed positively to its course, RA continues to present challenges to modern medicine. The discovery of tumor necrosis factor alpha (TNFα) as the central dogma in the pathogenesis of RA 11,12 resulted in broad consensus that anti-TNF biologics will be an effective treatment approach. Subsequently, anti-TNF biologic therapy did show significant improvements in the quality of life in majority of RA patients. 13,14 However, the concerns arose when an estimated 30%-40% of patients remained unresponsive to treatment while very few enjoyed complete remission. 15,16 Moreover, association of biologics with increased risk of adverse effects suggested the necessity of reviewing the effectiveness and safety of existing therapeutics. 17,18 Thus, this review exploits the comparison of effectiveness and safety of three prominent anti-TNFα biologics, infliximab, adalimumab and etanercept, aspiring to provide platform and background for the development of more effective and safer therapeutics. Pharmacotherapy According to the treatment guidelines published by the American College of Rheumatology, 19 goals of RA pharmacotherapy are; reduction of disease activity, establish remission, tight control through medical management and prevention of further joint damage. However, Alam et al 20 and Murphy et al 21 address improvement of the quality of life as another prominent goal. Traditionally, RA has been treated with non-steroidal antiinflammatory drugs (NSAIDs), glucocorticoids and diseasemodifying antirheumatic drugs (DMARDs). The NSAIDs and glucocorticoids remain first line drugs, whereas DMARDs are second line drugs. 22,23