CHALLENGES AND UMET NEEDS
ECONOMIC AND DISEASE BURDEN
RA imposes a considerable disease burden. Patients with RA have substantially lower health-related quality of life (QOL) than the general population (P<.05), with lower overall scores for physical and mental health across all age groups.1
- The RA disease burden also is associated with increased health care resource utilization.2
- Notably, RA patients with low QOL are twice as likely to be hospitalized as RA patients with high QOL2
- Direct medical costs alone for 7,527 patients with RA in 2001 were estimated at a mean annual total cost of $9,519 per patient.3
- RA results in high direct costs (medications, devices and hospitalizations), indirect costs (decreased productivity and reduced income) and intangible costs (reduced quality of life and premature mortality).
- Workers with RA had costs related to reduced work performance 2 to 4 times higher than workers without RA.4
Even before its clinical onset, patients with RA are at increased risk of coronary heart disease (CHD).5
- As CHD manifests differently in RA, a higher risk of unrecognized MI and sudden cardiac death is evident, along with a lower likelihood of angina symptoms.5
- Cardiovascular mortality is at least 1.5-fold higher in the RA population than in the general population, and it probably relates to a combination of differences in traditional cardiovascular risk factors and RA disease–related factors.6,7
RA-associated fatigue is rarely a target of treatment and has been infrequently assessed .8
- A study of 133 adults with longer duration of RA reports a high degree of fatigue that causes moderate distress, remains consistent during the course of a week, and affects discretionary and nondiscretionary activities of daily living.9
- Fatigue has also been found to be a strong indicator of overall health status, along with work dysfunctionality.10
Anemia of chronic disease also is common in RA patients, occurring in 40 to 49 percent of these individuals.11,12
- RA patients have been found to have anemia, particularly the presence of a low hemoglobin level at baseline, one of the independent contributors to disability and diminished physical function (P<.001).13
Between 1965 and 2005, mortality rates for patients with RA have remained relatively constant, at 2.4 and 2.5 per 100 person-years for women and men, respectively.14
- Mortality rates for women and men in the general population declined from 1.0 and 1.2, respectively, in 1965 to 0.2 and 0.3 in 2000.14
- Treatment strategies that seek to reduce the DAS to “low disease activity” or “remission” should be the treat-to-target goals in the care of patients with RA.
Although the achievable outcomes for RA continue to evolve and improve, not all patients are able to attain the desirable treatment goal of remission or, failing that, of low disease activity (LDA).15
- Following the introduction of the first biologic agent, many RA patients now have drugs available to them that effected a marked improvement in the quality of their lives, with a reduction of signs, symptoms, and structural progression of disease.
- No agent is universally effective in all patients with RA, reinforcing the need for additional agents that reduce RA’s joint inflammation and slow structural progression.
- Quantitatively-driven treatment of RA, aiming for a specific target of reduced disease activity, results in greater clinical improvement and a larger reduction in structural damage .16,17
- Success can be measured by the reduction in the Disease Activity Score (DAS), indicating the level of RA disease activity at a given point in time.
- Treatment strategies that advance therapy as to reduce the DAS to “low disease activity” or “remission” levels should be utilized during the care for RA patients.
Providing the right drug for the right patient at the right time is the goal of all pharmacotherapy, but numerous unmet needs continue to make it difficult to do so for patients with RA. Although there have been great strides in treatment, the evidence seems to support a need for more advanced therapies.
- Uhlig T, Loge JH, Kristiansen IS, Kvien TK. Quantification of reduced health-related quality of life in patients with rheumatoid arthritis compared to the general population. J Rheumatol. 2007;34:1241–1247.
- Ethgen O, Kahler KH, Kong SX, et al. The effect of health related quality of life on reported use of health care resources in patients with osteoarthritis and rheumatoid arthritis: a longitudinal analysis. J Rheumatol. 2002;29:1147–1455.
- Michaud K, Messer J, Choi HK, Wolfe F. Direct medical costs and their predictors in patients with rheumatoid arthritis: a three year study of 7,527 patients. Arthritis Rheum. 2003;48:2750–2762.
- Braakman-Jansen LM, Taal E, Kuper IH, van de Laar MA. Productivity loss due to absenteeism and presenteeism by different instruments in patients with RA and subjects without RA. Rheumatology (Oxford). 2012;51(2):354-356.
- Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum.2005;52:402–411.
- Gonzalez A, Kremers HM, Crowson CS, et al. Mortality trends in rheumatoid arthritis: the role of rheumatoid factor. J Rheum. 2008;35(6):1009-1014.
- McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219.
- Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. 2012;51:v3-v11.
- Kremer J, Genovese M, Keystone E, et al. Effects of baricitinib on lipid, apolipoprotein, and lipoprotein particle profiles in a phase IIb study of patients with active rheumatoid arthritis. Arth Rheum. 2017; 69: 943-952.
- Hürlimann D, Forster A, Noll G, et al. Anti-Tumor Necrosis Factor-Treatment Improves Endothelial Function in Patients With Rheumatoid Arthritis. Circulation. 2002;106:2184-2187.
- Barnabe C, Martin B, Ghali W. Systematic review and meta-analysis: anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63:522-529.
- Greenberg J, Kremer J, Curtis J, et al; CORRONA Investigators. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:576-582.
- Solomon D, Rassen J, Kuriya B, et al. Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonis Ann Rheum Dis. 2013 72: 1813-1818.
- Kume K, et al. Tocilizumab monotherapy reduces arterial stiffness as effectively as etanercept or adalimumab monotherapy in rheumatoid arthritis: an open-label randomized controlled trial. J Rheumatol. 2011;38(10):2169–21
- Kume K, Amano K, Yamada S, et al Tocilizumab Improves Left Ventricular Mass and Cardiac Output in Patients With Rheumatoid Arthritis. A Cohort Study. ACR/AHRP Annual Meeting, San Diego, October Abstract 1410.
- Kalyoncu U, Dougados M, Daurès JP, Gossec L. Reporting of patient reported outcomes in recent trials in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis. 2009;68:183–190.
- Belza BL, Henke CJ, Yelin EH, et al. Correlates of fatigue in older adults with rheumatoid arthritis. Nursing Research. 1993;42:93–99.
- Wolfe F, Hawley DJ, Wilson K. The prevalence and meaning of fatigue in rheumatic disease. J Rheumatol. 1996;23:1407–1417.
- Davis D, Charles PJ, Potter M, et al. Anaemia of chronic disease in rheumatoid arthritis: In vivo effects of tumour necrosis factor α blockade. Br J Rheum. 1997;36:950–956.
- Peeters HRM, Jongen-Lavrencic M, Raja AN, et al. Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset. Ann Rheum Dis. 1996;55:162–168.
- Han C, Rahman MU, Doyle MK et al. Association of anemia and physical disability among patients with rheumatoid arthritis. 2007;34:2177–2182.
- Kim S, Schneeweiss S, Liu J, Solomon D. The risk of thromboembolism in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013; 65: 1600-1607.
- Bacani A, Gabriel S, Crowson C, et al. Noncardiac vascular disease in rheumatoid arthritis: Increase in venous thromboembolic events? Arthritis Rheum. 2012; 64: 53-61.
- Korswagen L, Bartelds G, Krieckaert C, et al. Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study. Arthritis Rheum. 2011; 63: 877-883.
- Gonzalez A, Maradit-Kremers H, Crowson CS, et al. The widening mortality gap between rheumatoid arthritis and the general population. Arthritis Rheum. 2007;56:3583–3587.
- Taylor PC, Moore A, Vasilescu R, et al. A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective. Rheumatol Int (2016) 36:685–695.
- Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in rheumatoid arthritis: a randomized trial. Ann Intern Med.2007;146: 406–415.
- Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomized control trial. Lancet.2004;364: 263–269.