ROLE OF IL-6

IL-6 is one of the most abundant cytokines in the synovial fluid of patients with rheumatoid arthritis (RA) and plays a critical role in RA disease progression.1,2

ELEVATED IL-6 IN RA HAS WIDESPREAD ARTICULAR AND SYSTEMIC EFFECTS2

  • IL-6, a multifunctional cytokine, works via a dual signaling mechanism (classical or cis-signaling and trans-signaling)
  • When persistently elevated in RA, IL-6 can disrupt homeostasis in a wide variety of physiological processes

Persistently elevated IL-6 levels can contribute to structural damage, fatigue, morning stiffness, and other articular and systemic effects of RA2,3

Continuously high levels of IL-6 in rheumatoid arthritis patients have damaging articular and systemic effects Continuously high levels of IL-6 in rheumatoid arthritis patients have damaging articular and systemic effects
In a single-center controlled study, mean serum IL-6 levels were approximately 10x higher in patients with RA (n=66) than in control group (n=24)5*
  • *Serum concentrations of IL-6 were measured in healthy subjects and adult patients with RA and the levels were correlated with disease activity.5

IL-6=interleukin-6; RA=rheumatoid arthritis; CRP=C-reactive protein.

NEARLY 50% OF RA PATIENTS ARE UNCONTROLLED ON CURRENT TREATMENT

Patients with uncontrolled RA may be identified in different ways, such as showing inadequate clinical response or having to switch or discontinue current treatment6-8

Up to 40% of RA patients are unable to achieve adequate clinical response (ACR20) despite treatment with a TNF inhibitor Up to 40% of RA patients are unable to achieve adequate clinical response (ACR20) despite treatment with a TNF inhibitor

are unable to achieve adequate clinical response (ACR20) despite treatment with a TNF inhibitor, leading them to experience some degree of limitation in their daily lives6

OF PATIENTS DISCONTINUE OR SWITCH TO A NEW BIOLOGIC at 1 year of initiating their first biologic7,8

Recent ACR and EULAR RA treatment guidelines conditionally recommend switching MOA as a treatment option for TNF-IR patients9,10*

If treatment target of remission or low disease activity is not achieved in patients with moderate or high disease activity despite the use of MTX or a TNF inhibitor:

  • Treat with a biologic agent with another mechanism of action or a second TNF inhibitor
  • *2015 American College of Rheumatology Guidelines and 2016 EULAR Recommendations.

ACR20=American College of Rheumatology 20% improvement criteria; TNF=tumor necrosis factor; EULAR=European League Against Rheumatism; MOA=mechanism of action; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; MTX=methotrexate.

References:

  • KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.
  • Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24.
  • Perry MG, Kirwan JR, Jessop DS, Hunt LP. Overnight variations in cortisol, interleukin 6, tumour necrosis factor alpha and other cytokines in people with rheumatoid arthritis. Ann Rheum Dis. 2009;68(1):63-68.
  • Arvidson NG, Gudbjörnsson B, Elfman L, et al. Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. Ann Rheum Dis. 1994;53:521-524.
  • Robak T, Gladalska A, Stepień H, Robak E. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Mediators Inflamm. 1998;7(5):347-353.
  • Kukar M, Petryna O, Efthimiou P. Biological targets in the treatment of rheumatoid arthritis: a comprehensive review of current and in-development biologic disease modifying anti-rheumatic drugs. Biologics. 2009;3:443-457.
  • Bonafede MM, Curtis JR, McMorrow D, Mahajan P, Chen CI. Treatment effectiveness and treatment patterns among rheumatoid arthritis patients after switching from a tumor necrosis factor inhibitor to another medication. Clinicoecon Outcomes Res. 2016;8:707-715.
  • Gu T, Mutebi A, Stolshek BS, Tan H. Cost of biologic treatment persistence or switching in rheumatoid arthritis. Am J Manag Care. 2018;24(8):SP338-SP345.
  • Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1)1-26.
  • Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-977.