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 EFFECTS1,2

  • 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 RA2-5*

Elevated levels of IL-6 in RA patients lead to many disruptive symptoms such as pain, elevated CRP, low hemoglobin levels, tender and swollen joints, joint destruction, morning stiffness, and increased osteoclast activity.  Evidence shows IL-6 levels are 4x higher during early morning hours in RA patients. Elevated levels of IL-6 in RA patients lead to many disruptive symptoms such as pain, elevated CRP, low hemoglobin levels, tender and swollen joints, joint destruction, morning stiffness, and increased osteoclast activity.  Evidence shows IL-6 levels are 4x higher during early morning hours in RA patients.
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)7‡
  • *Placement of systemic and articular labels on image is for illustrative purposes only.
  • The study results demonstrated that the circulating levels of IL-6 were increased in the morning in patients with RA and declined from early in the afternoon to late in the evening.6
  • Serum concentrations of IL-6 were measured in healthy subjects and adult patients with RA and the levels were correlated with disease activity.7

IL-6=interleukin-6; 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 treatment.8-10

Up to 40% of RA patients 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 lives. Up to 40% of RA patients 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 lives.

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 lives8

40% to 53% of patients discontinue or switch to a new biologic at 1 year of initiating their first biologic 40% to 53% of patients discontinue or switch to a new biologic at 1 year of initiating their first biologic

of patients discontinue or switch to a new biologic at 1 year of initiating their first biologic9,10

Recent ACR and EULAR RA treatment guidelines conditionally recommend switching MOA as a treatment option for TNF-IR patients11,12*

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.
  • Chernoff D, Eastman PS, Hwang CC, et al. Determination of the minimally important difference (MID) in multi-biomarker disease activity (MBDA) test scores: impact of diurnal and daily biomarker variation patterns on MBDA scores. Clin Rheumatol. 2019;38(2):437-445.
  • Hambardzumyan K, Saevarsdottir S, Bolce R, et al. A multi-biomarker disease activity (MBDA) score and the 12 individual biomarkers in early rheumatoid arthritis patients relate differently to clinical response and radiographic progression: results from the SWEFOT trial. Poster presented at the EULAR Annual European Congress of Rheumatology Meeting; June 12-15, 2013; Madrid, Spain
  • Arvidson NG, Gudbjörnsson B, Elfman L, Rydén AC, Tötterman TH, Hällgren R. Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. Ann Rheum Dis. 1994;53(8):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 biological disease modifying anti-rheumatic drugs. Biologics. 2009;3:443-457.
  • Bonafede M, Johnson BH, Tang DH, Harrison DJ, Stolshek BS. Compliance and cost of biologic therapies for rheumatoid arthritis. Am J Pharm Benefits. 2017;9(5):e1-e7.
  • 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 RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. doi:10.1136/annrheumdis-2019-216655.