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Rheumatoid Arthritis: Understanding treatment options

Pain, Inflammation, Joint disorders | April 13, 2015 | Author: The Super Pharmacist

Inflammation, Pain

Rheumatoid Arthritis: Understanding treatment options

Rheumatoid arthritis is a condition in which the protective cartilage within joints wears away (or degenerates) over time. This may proceed to a point at which the surfaces (or 'ends') of two bones that make up a joint are exposed rather than being coated with cartilage and results in increases in friction, decreases in normal motility and flexibility, and increased pain in the affected joint and is associated with significant reductions in functional status. Rheumatoid arthritis typically affects the hip joints and joints toward the periphery of the body, i.e. the fingers or knees and is also strongly associated with advancing age, with most cases diagnosed in people of 65 years or more.

Currently, there is no outright cure for the condition, with treatment focusing on reducing the mechanisms of cartilage loss, thus slowing or stopping the progression of the disease. 

Progression of the disease

  • Autoimmune activity: This condition is characterised by the destruction of cartilage by components of the body's own immune system, which 'mistake' this tissue for 'foreign', harmful particles.
     
  • Inflammation: Rheumatoid arthritis is associated with increased inflammation in affected joints. This is stimulated by the autoimmune response, as above. Inflammatory molecules may also be released by damaged cartilage, which may impair healing in this tissue. This further contributes to its degeneration.

The symptoms of rheumatoid arthritis, mostly associated with this autoimmune and inflammatory activity, include:

  • Pain (due to nerve damage and adverse stimuli associated with inflammation)
  • Redness in the skin above affected joints
  • The perception of increased temperature in affected joints or the tissues around them
  • Increased stiffness in the affected joint
  • Impaired mobility in the joint

Treatment for this condition may be established and conventional, novel, or variations on existing treatments. Due to the diversity of location, progression of the disease, age of the patient and effects on one's quality of life, treatment needs to be individualised.

Treatments for Rheumatoid Arthritis

Arthroplasty

This is a surgical technique reserved for severe and/or advanced cases of rheumatoid arthritis, most often applied to the hip or knee joint. It is the total or partial replacement of joint surfaces with medical prostheses or other products. Arthroplasty is a safe and effective treatment in many cases, but may be associated with adverse events such as the failure of integration of new implants or materials with the rest of the existing joint ('slippage' or 'loosening'). This may be associated with infection (e.g. 'septic slippage').

A trial compared a new technique of more extensive cementing of a knee prosthesis to the tibia, rather than surface cementing as is a conventional practice. The outcome measure (the lack of aseptic loosening at a ten-year follow-up) was shown to be 100% for the 'surface' group, compared to 93% in the full cementing group. Patient satisfaction was also significantly greater in the first group compared to the second.

Corticosteroids

These drugs reduce inflammation, and may therefore effectively alleviate symptoms including pain and redness in cases of rheumatoid arthritis.

These drugs can be administered orally to treat this condition. Corticosteroid injection therapies, in which the drugs are delivered directly into the joint via needle, are an increasingly common strategy. These are also known as intra-articular or joint injections. These injections, which may also include local anesthetics to numb damaged nerves, are effective and safe in most cases.

However, corticosteroids are associated with a range of side effects and adverse effects. These may include gastric ulceration and bleeding, hormonal changes resulting in metabolic, neurological or physiological changes, and immunosuppression. The risks of these adverse effects increase with the concentration and/or frequency of the doses of steroids administered. Other more rare events include the development of sepsis, necrosis or infections in the joint in question.

Disease-Modifying Anti-Rheumatic Drugs (DMARD's)

These are Disease-Modifying Anti-Rheumatic Drugs. DMARDs are divided into two main categories:

  • conventional (or synthetic) DMARDs or
  • biologic DMARDs.

Conventional DMARDs include chemicals such as methotrexate. Some research indicates that approximately 33% of patients are resistant to treatment with conventional DMARDs. The main advantage of this therapy is cost, particularly compared to those of newer biologic DMARDs.

Biologic DMARDs may include drugs that bind to or inhibit molecules involved in the auto-immune response and/or inflammation. These molecules may include tumour necrosis factor-alpha (TNFalpha), a cytokine involved in the stimulation of inflammation. Drugs that inhibit this molecule may lead to improvement in cases of rheumatoid arthritis.

A review of trials investigating this strategy indicates that anti-TNFalpha therapy is associated with safety and some efficacy in patients aged both younger and older than 65 years. An analysis of data from over 1500 patients treated with anti-TNFalpha agents found that this therapy resulted in decreases in disease progression in patients both under and over 65 years, but in less functional improvement in the 'older' group compared with 'younger' group.

However, the inhibition of TNFalpha may lead to increased immune system suppression.

Co-administration of TNFalpha antagonists and corticosteroids

The co-administration of TNFalpha antagonists and corticosteroids may be associated with significant increases in the risk of infections in older patients.

An analysis of the incidence of infections in 341 patients found that the combination of anti-TNFalpha agents and other DMARDs doubled this risk, and the combination of corticosteroids with both treatments increased the risk of infection by 2.5 times.

The combination of TNFalpha with corticosteroids tripled the risk of infection. However, the risk of infection with any drug may be influenced by other factors, which include the severity of arthritis, and female gender.

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References

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Schlegel UJ, Bruckner T, Schneider M, Parsch D, Geiger F, Breusch SJ. Surface or full cementation of the tibial component in total knee arthroplasty: a matched-pair analysis of mid- to long-term results. Archives of orthopaedic and trauma surgery. 2015.

Ciriaco M, Ventrice P, Russo G, et al. Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother. 2013;4(Suppl 1):S94-98.

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Lampropoulos CE, Orfanos P, Bournia VK, et al. Adverse events and infections in patients with rheumatoid arthritis treated with conventional drugs or biologic agents: a real world study. Clinical and experimental rheumatology. 2015.

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Genevay S, Finckh A, Ciurea A, Chamot AM, Kyburz D, Gabay C. Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study. Arthritis and rheumatism. 2007;57(4):679-685.

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Germano V, Cattaruzza MS, Osborn J, et al. Infection risk in rheumatoid arthritis and spondyloarthropathy patients under treatment with DMARDs, corticosteroids and TNF-alpha antagonists. Journal of translational medicine. 2014;12:77.

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