Clinical Updates in Rheumatoid Arthritis: New Perspectives on Targeting Remission and Individualizing Therapy

RA is a chronic, progressive inflammatory autoimmune disease producing both articular and extra-articular manifestations.1,2 Of note, studies have shown that mortality risks are 50% higher in people with RA compared with the general population.3 The differential responses seen with current treatment modalities suggest that overlapping signaling pathways driven by proinflammatory cytokines can control the characteristic autoreactivity and other clinical manifestations of RA.4 In particular, elevated levels of interleukin-6 (IL-6) and its receptor are found in affected joints, where they contribute to cartilage damage and bone erosion.5 Additionally, signaling via soluble IL-6 receptor likely contributes to the systemic inflammatory effects of RA.6 Adopting treat-to-target strategies and actively targeting remission in each patient has shown great promise in improving RA outcomes, but up to 40% of patients do not adequately respond to conventional disease-modifying antirheumatic drugs (DMARDs) or inhibitors of tumor necrosis factor.6 These data highlight the need for other options, including 2 biologic DMARDs that are specific for the IL-6 receptor.6,7 This Clinical Research Updates™ activity has been developed to update clinicians on the latest evidence-based information to guide RA management, with a focus on inhibition of IL-6 signaling.

References:
1. Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15-25.

2. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51 (suppl 5):v3-v11.

3. Young A, et al. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology (Oxford). 2007;46(2):350-357.

4.Goetz I, et al. Review of treatment response in rheumatoid arthritis: assessment of heterogeneity. Curr Med Res Opin. 2011;27(4):697-711.

5. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24.

6. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford)Bykerk VP, et al. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Ann Rheum Dis. 2012;71(12): 1950-1954. 2010;49(1):15-24.

7. Burmester GR, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847.