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Welcome! This Learning unit provides you with an overview of RA

Here you will be reminded of how many people are affected by RA, learn about the role that genetic, environmental and autoimmune factors play in the pathophysiology of RA, the key effector cells in RA that arise from the immune system and the wider burden of RA.

RA affects about 0.5% of adults worldwide(1)

RA affects approximately 0.5%of adults worldwide.(1) In the UK, approximately 1% of people live with RA.(2) RA is more common in women than men, around 1.5 men and 3.6 women develop RA per 10,000 people per year, which translate into approximately 12,000 people developing RA per year in the UK.(3)

According to the Norfolk Arthritis Register (NOAR), patients with RA in the UK have higher rate of mortality compared with the general population.(4)

The Pathophysiology of RA

RA is a heterogeneous complex disease in clinical presentation, pathobiological processes and response to targeted therapies.(5-10)

Genetic environmental and autoimmune factors underlie the pathogenesis of RA.(11)

Drag the slider below to reveal how an environmental factor such as smoking affects the pathogenesis of RA over time

TIME

Genetic and environmental factors that underlie the pathogenesis of RA(11)

Adapted from Klareskog L, et al. Lancet 2009.(11)


RA is a complex syndrome with a multifactorial aetiology and emerging data suggest that the microbiome may influence this disease. DNA sequence-based analyses of gut microbiota suggest that the microbiome may influence autoimmune disease manifestation.6,7

The microbiome may influence the development of RA(7)

Adapted from Scher and Abramson. Nat Rev Rheumatol 2011.(7)

Cytokine networks play a role in the pathogenesis of RA

As seen in the figure, most key effector cells in RA arise from the immune system. B cells, T cells, macrophages, chondrocytes, osteoclasts, synovial fibroblasts and hepatocytes all play a central role in the pathogenesis of RA.6,12-14

Cytokines, small peptides that allow communication between cells, drive the inflammatory response of RA.15,16 A complex cytokine network balances proinflammatory and anti-inflammatory effects. In RA, proinflammatory cytokines predominate, but this effect is not constant.

Many proinflammatory cytokines play a role in the pathogenesis of RA.

RA affects the whole person

RA is a complex disease that affects the whole person with an impact well beyond joints, including an increased risk of cardiovascular disease, infection and osteoporosis.5-7,17,18

Click on the icons below to investigate the impact RA has on a patient.

Impact of RA(1,6,17-22)

RA Symptoms have an impact on patients' lives

RA has a socioeconomic and economic impact.(17,23)

In the UK, approximately one-third of patients cease work because of RA within two years of onset, and this prevalence increases thereafter.(3)

The total cost of RA in the UK, including indirect costs and work-related disability, has been estimated at between E3.8 billion and £4.75 billion per year.(3)

RA impacts the quality of life (QoL) of patients in various ways:(21)
- Impacts moods, emotions, social life, hobbies, everyday tasks, personal and social relationships and physical contact
- Limits mobility und restricts travel
- Increases dependence on others, leading to feelings of helplessness
- Can lead to anger and frustration arising from the

PAIN
Pain is a major issue for patients with RA, with 63% stating they experience pain every day and the majority looking for new, more effective pain management(24)
FUNCTIONAL DISABILITY
RA has an adverse effect on everyday activities for many patients; 60% of patients report difficulties in performing ‘normal’ tasks because of RA(24)
FATIGUE

Fatigue is a major problem for patients with RA, with around one in four patients from the QUEST-RA* database scoring high on the fatigue score(2,6)


Increased fatigue scores were associated with:
• Comorbidity burden
• Disease activity
• Disability

* The QUEST-RA programme was established in 2005 to promote quantitative assessment in RA care at multiple sites and develop a database of RA patients seen in regular care across several countires.

The management of RA remains a clinical challenge

Despite key strategic developments and treatment advances in the past 15 years, RA still remains a clinical challenge.(27) Data included in the EULAR recommendations show that the best outcomes are achieved with:(27,28)


Click on the numbers below to see how the best outcomes may be achieved when treating RA

Non-Responders

Parenterally administered, targeted biologic therapies, usually given with concomitant methotrexate, have permitted improved responses in some, but not all, patients.(6,27)

The heterogeneity of pathological drivers in RA is reflected in a consistent proportion of primary non-responders to any given targeted biologic intervention.(29,30)

Persistently active disease remains a problem for some other RA patients who respond only partially to biologic therapy.6 A delay in the assessment of patients with early RA may have a long-term impact.(31)


Management of RA

In the UK, the NICE clinical guidelines detail recommendations for the management of RA in adults.3 These guidelines can be accessed here: https://www.nice.org.uk/guidance/cg79.

The future for RA treatment(6,32-36)

The discovery of key intracellular pathways in the pathogenesis of RA has ushered in a new stage of drug development.

If you are interested in finding out more on this topic, read the learning unit ‘Intracellular signalling pathways in RA’.

Knowledge Check

Recap what you have read in this learning unit by completing the short knowledge check below, selecting the correct response for each question.

Question 1
Which cells play a role in the pathogenesis of RA?
Submit answer
Question 2
From the list below, select a proinflammatory cytokine that play a role in the pathogenesis of RA:
Submit answer
Question 3
According to a patient survey carried out in 2015, pain is one of the three most important concerns for patients with RA. How many patients report experience pain every day?
Submit answer
Question 4
According to a patient survey carried out in 2015, how many patients with RA report experiencing high levels of fatigue>
Submit answer
Question 5
How are the best outcomes achieved when treating RA?
Submit answer

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  1. Carmona L, et aL Best Pract Res On Rheumato12010;24:733-45.
  2. NRAS: About RA., key facts. Available at: http://www.nras.org.uk/for-journalists. Last accessed: December 2017.
  3. Rheumatoid arthritis in adults: management (CG79). NICE clinical guidelines (February 2009).
  4. Humphreys JH, et al. Arthritis Care Res 2014;66:1296-301.
  5. McInnes IB, et aL Ann Rheum Dis 2015;74:694-702.
  6. McInnes IB and Schett G. N EngIJ Med 2011;365:2205-19.
  7. Scher JU and Abramson SB. Nat Rev Rheumatol 2011;7:569-78.
  8. Yahya A, et al. Mod Rheumatol 2014;24:271-4.
  9. Stolt P, et a/. Ann Rheum Dis 2010;69:1072-6.
  10. Aletaha D, et aL Arthritis Rheum 2010;62:2569-81.
  11. Klareskog L, et al. Lancet 2009;373:659-72.
  12. Hematopoietic stem cells. Available at: https://stemcells.nih.govimfo/2001report/chapter5.htm. Last accessed: December 2017.
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  16. Chizzolini C, et at. Arthritis Res Ther 2009;11:246.
  17. Sokka T, et al. Arthritis Res Ther 2010;12:R42.
  18. Listing J, et al. Rheumatology (Oxford) 2013;52:53-61.
  19. Doron MF, et al. Arthritis Rheum 2002;46:2287-93.
  20. Franklin J. et al. Ann Rheum Dis 2007:66:308-12.
  21. Whalley D, et al. Br j Rheumatol 1997;36:884-8.
  22. Lindhardsen J, et al. Ann Rheum Dis 2001;70:929-34.
  23. Hansard, Arthritis, Col. 308W, 9th July 2014. Available at: http://www.publications.parliamentuk/ pa/cm201415/cmhansrd/chan21.pdf. Last accessed: December 2017.
  24. Strand V, et a/. J Rheumatol 2015;42:2046-54.
  25. Gossec L, et al. Ann Rheum Dis 2009;68:1680-5.
  26. Gran KL, et al. Clin Exp Rheumatol 2014;32:869-77.
  27. Smolen JS, et al. Ann Rheum Dis 2017;7:960-77.
  28. Goekoop-Ruiterman YP and Huizinga TW. Nat Rev Rheumatol 2010;6:68-70.
  29. Tak PT. Rheumatology 2012;51:600-9.
  30. Burska AN, et at. Pharmacogenornics J 2014;14:93-106.
  31. van der Linden MP, et al. Arthritis Rheum 2010;62:3537-46.
  32. Norman P. Expert Opin Investig Drugs 2014;23:1067-77.
  33. Siebert S, et al. Pharmacol Rev 2015;67:280-309.
  34. Schett G, et al. Nat Med 2013;19:822-4.
  35. O'Shea JJ, et al. Annu Rev Med 2015;66:311-28.
  36. Boyle DL, et al. Ann Rheum Dis 2015;74:1311-6.

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ACPA=anti-citrullinated peptide antibody; ATP=adenosine triphosphate; CCLS=CC chemokine ligand 5; FGF=fibroblast growth factor; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; IL=interleukin; LT4ymphotoxin; M-CSF=macrophage colony-stimulating factor; MI-myocardial infarction; MMIF-macrophage migration inhibitory factor; NICE=National Institute for Health and Care Excellence; PSA=psoriatic arthritis; QoL=quality of life; QUEST-RA=Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis; RA=rheumatoid arthritis; RF=rheumatoid factor; SAA=serum amyloid A; SFB=segmented filamentous bacteria; TGF=transforming growth factor; TNF=tumour necrosis factor; VEGF=vascular endothelial growth factor.

©2018 Eli Lilly and Company. All rights reserved. The Olumiant mark and Olumiant design are the trademarks of Eli Lilly and Company.