Rheumatoid arthritis


Rheumatoid arthritis (RA) affects up to 1% of the population and tends to manifest between the ages of 20 and 40 years. It is more common in women and developing countries.1

Treatment guidelines emphasize the importance of early intervention to prevent joint damage and more severe consequences such as pain and deformity.2

RA has an estimated total annual economic burden of EUR 45.3 billion in Europe and EUR 41.6 billion in the USA.3

Burden of RA

The burden of RA may be substantial and extends beyond the joints

A systematic review found that RA is associated with multiple comorbidities and psychosocial impairments:4

HRQoL, health-related quality of life.

Adapted from Cutolo et al 2014.


RA has implications for quality of life and ability to work

Quality of life
  • HRQoL is impaired in RA owing to pain, fatigue, and functional deficits4
  • The reduction in HRQoL is associated with decreased productivity, work loss and work disability4
  • Depression in patients with RA is associated with increases in mortality, cardiovascular morbidity, and disability4
  • Depression is common amongst patients with RA, with an estimated prevalence of up to 20%4
Work ability
  • Many patients with RA stop working within several years of disease onset5
  • Work disability has been related to treatment response, with the highest rates observed in non-responders4
  • Surgery may be needed in refractory patients to relieve pain, restore function, and prevent/correct deformity6

HRQoL, health-related quality of life; RA, rheumatoid arthritis. 


Optimal management includes both non-pharmacological and pharmacological therapy

In terms of pharmacological management:

  • Guidelines recommend an aggressive and tailored approach
  • Early use of disease-modifying anti-rheumatic drugs (DMARDs) is associated with higher chance of reaching remission/treatment success, and can prevent early joint damage
  • Physiotherapy, ergotherapy, orthopedic surgery
  • Preventative measures to reduce risk of cardiovascular disease and osteoporosis
  • Psychological and social assistance
  • Patient education (nutritional counseling, smoking cessation programs)


First-line pharmacological therapy: csDMARDs

  EULAR recommendations
csDMARDs are first-line therapy Should be used immediately after diagnosis
Options include:
  • MTX
Should be part of the first-line treatment strategy in patients with active RA
  • Sulfasalazine
Where there are contraindications (or early intolerance) to MTX, these should be considered as part of the first-line treatment strategy
  • Leflunomide
Combination with glucocorticoids
  • Glucocorticoids
Should be considered when initiating csDMARDs, in different dose regimens and routes of administration, but should be tapered as rapidly as clinically feasible

csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; EULAR, European League Against Rheumatism; MTX, methotrexate.

Adapted from Smolen et al, 2017.2

Biologic DMARDs: Anti-tumor necrosis factor (anti-TNFs antibodies)

Since the introduction of the first anti-TNF in the early 1990s, biologic therapies have given relief to patients when conventional DMARDs have failed.8

Mode of action of anti-TNFs

s/tmTNF, soluble/transmembrane tumor necrosis factor; TNFRI/II, tumor necrosis factor 1/2.

Adapted from Moss et al, 20089 and Tracey et al, 2008.10


  • Bind soluble and transmembrane TNF-α
  • Prevent TNF-α from interacting with its two receptors (TNFRI and TNFRII)
  • Prevent TNF-α mediated signaling
  • Induce transmembrane TNF-mediated mechanisms, such as apoptosis, reverse signaling (resulting in cytokine suppression), and antibody and cell-dependent cytotoxicity

Biologic DMARDs: Other targets

  • Non-TNF bDMARDs include abatacept, rituximab, tocilizumab, and sarilumab. Abatacept and rituximab prevent T- and B-cell activation, respectively, and sarilumab and tocilizumab interfere with interleukin (IL)-6 signaling11

Targeted synthetic DMARDs: Janus kinase (JAK) inhibitors

  • JAK inhibitors tofacitinib and baricitinib have demonstrated efficacy in RA and were recently included in the EULAR2 and American College of Rheumatology (ACR) guidelines7
  • Tofacitinib and baricitinib are approved in the European Union for the treatment of moderate-to-severe RA12,13

IL, interleukin; TNF, tumor necrosis factor.

Adapted from Scott 201210 and Tanaka 2016.14


The 2016 update of the European League Against Rheumatism recommendations reflect the recent changes in the treatment paradigm of RA

General principles

  • Start DMARD therapy:2
    • Immediately upon diagnosis
  • Treatment goal:2
    • Remission
    • Low disease activity, if refractory
  • Frequent monitoring:2
    • Every 1–3 months in active disease
  • Adjustment of therapy:2
    • If no improvement within 3 months of treatment initiation
    • If target not reached by 6 months


(b/cs)DMARD, (biologic/conventional synthetic) disease-modifying anti-rheumatic drug; JAK, Janus kinase; MTX, methotrexate.

Adapted from Smolen et al, 2017.2

*Risk factors include a high disease activity state, autoantibody positivity (rheumatoid factor and/or antibodies to citrullinated proteins) and the early presence of joint damage. 

csDMARDs include MTX, sulfasalazine and leflunomide. bDMARDs include anti-TNFs (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept or tocilizumab, and, under certain circumstances, rituximab.


Additional information

You can find additional information about RA by following these links:

NHS Choices:

National Rheumatoid Arthritis Society:

American College of Rheumatology:

1. World Health Organization. Chronic rheumatic conditions. http://www.who.int/chp/topics/rheumatic/en/ [Accessed Nov 27, 2018].

2. Smolen JS, et al. Ann Rheum Dis. 2017;76:960–77. 

3. Taylor P, et al. Rheumatology Int. 2016;36(5):685–95.

4. Cutolo M, et al. Semin Arthritis Rheum. 2014;43:479–88.

5. Barrett EM, et al. Rheumatology. 2000;39:1403–9.

6. Chim HW, et al. J Hand Ther. 2014;27:134–42.

7. Singh JA, et al. Arthritis Care Res (Hoboken). 2016;68:1–25.

8. Penn H. Clin Med. 2006;6:105–8.

9. Moss ML, et al. Nat Clin Pract Rheumatol. 2008;4:300–9.

10. Tracey D et al. Pharmacol Ther. 2008;117:244–79.

11. Scott DL. Clin Pharmacol Ther. 2012;91:30–43.

12. European Medicines Agency. Xeljanz (tofacitinib) Summary of Product Characteristics. https://www.ema.europa.eu/documents/product-information/xeljanz-epar-product-information_en.pdf [accessed Nov 27, 2018].

13. European Medicines Agency. Olumiant SmPC. https://www.ema.europa.eu/documents/product-information/olumiant-epar-product-information_en.pdf [accessed Nov 27, 2018].

14. Tanaka Y. Korean J Intern Med. 2016;31:210-8.

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