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Juvenile Arthritis - A clinical overview of treatment options

Pain, Infant and Children | August 27, 2014 | Author: The Super Pharmacist

Children

Juvenile Arthritis - A clinical overview of treatment options

Juvenile arthritis is the most common paediatric soft tissue condition, affecting approximately 1 in 1000 children. The condition is known by a number of names, including juvenile rheumatoid arthritis, but current research and institutional recommendations tend to place the condition under the umbrella term 'juvenile idiopathic arthritis'.

This condition features a range of subtypes and symptom profiles, and is treated with a range of medications. These are rapidly diversifying to address the specific biochemical mechanisms emerging in childhood arthritis. The more established and evidence-based treatments will be discussed in this article.

What is Juvenile idiopathic arthritis?

Juvenile idiopathic arthritis (JIA) is characterised by pain, swelling, discomfort and/or reduced mobility in joints occurring before the age of 16 and in the absence of the diagnosis of any other movement disorder.

Other diagnostic criteria of JIA include the persistence of these symptoms for at least six weeks; in other words, it is often a chronic condition. It may also occur in recurrent 'flares', in which symptoms recede for a period of time and then return in force.

Like all forms of arthritis, JIA may involve the progressive degeneration of joint tissue.

The underlying cause is unknown, but it is associated as an acquired autoimmune reaction or autoimmune disease state.

This discovery had led to the proposal of JIA categorisation into several subtypes, based on the immune protein or cell that is dysfunctional in the course of the disease. For example, one discrete type may be associated with synovial inflammation due to an imbalance between counts of 'pro-inflammatory' and 'anti-inflammatory' immune cells.

Another type is associated with abnormalities in the functions of immune proteins called interleukins.

Some institutions sort cases of the condition into more defined categories, based on the joints affected, type of onset and/or relevant biological markers. These include:

  • Rheumatoid-Factor Negative Polyarthritis
  • Rheumatoid-Factor Positive Polyarthritis
  • Enthesitis-Related Arthritis
  • Undifferentiated Arthritis
  • Oligoarthritis
  • Systemic-Onset Arthritis
  • Psoriatic Arthritis

This condition may have significant effects on the quality of life (QOL), function and development of the patients affected. It may also have an adverse effect on the psychological well-being of the patient and family members. JIA may also contribute to sleep disturbances, which in turn may be associated with further detriments in patient QOL.

Risk factors for Juvenile Arthritis

JIA may be associated with a number of risk factors, including:

  • Genes: Variations in a number of genes, mostly concerned with the human immune response, are associated with the development of JIA
  • UV radiation exposure
  • Microbial exposure in earlier life or at JIA onset
  • Vitamin D deficiency
  • Maternal smoking during pregnancy

However, more research is needed before any of these are proven to be causative factors in JIA.

Treatment for Juvenile Arthritis

Following a diagnosis of JIA, the doctor should discuss and agree upon treatment options, goals and expectations for the child and their family.

Currently, there is no effective cure for the condition, as the exact causative factors have not yet been confirmed. Therefore, regimens that achieve full remission and amelioration of symptoms are the object in JIA treatment.

Unfortunately, symptoms such as joint deterioration, impaired physical function and reduced QOL may persist despite treatment, and may last into adulthood. Therefore, JIA patients and their parents may need to manage their expectations accordingly. 

Consistent adherence to treatment is associated with improved outcomes, especially in cases where JIA arises in flares.

There are a number of treatment options for the management of JIA, most of which target inflammation, pain and/or the retention of joint integrity.

Treatment Options

Non-steroidal anti-inflammatory drugs (NSAIDs)

These medications reduce inflammation and are a typical first-line treatment in conditions such as JIA. They may be most suitable for cases in which symptoms are relatively mild, with little joint damage and low probability of persisting into later life. However, prolonged NSAID use is associated with side-effects such as gastrointestinal damage; therefore, they are not recommended for long-term therapy.

Steroid medications

Steroid medications also inhibit inflammation, and may also contribute to joint maintenance in JIA. Steroids may be given orally or via injection directly into an affected joint, which may be associated with more effective and long-term relief from symptoms. Injectable triamcinolone formulations are most often recommended for use in JIA treatment.

Treatment for Juvenile ArthritisInjections are regarded as effective for many subtypes of arthritis, regardless of symptom severity or progression. A successful injection is effective for approximately four months, and may be repeated at subsequent four-month intervals. Severe cases may be addressed with systemic injection (into the bloodstream). JIA patients who do not respond to this option may consider the next line in treatment, DMARDs.  

Disease-modifying anti-rheumatic drugs (DMARDs)

DMARDs are medications designed to inhibit inflammation, or immune-cell activity, in autoimmune joint conditions. There are 2 main types; biologic and non-biologic DMARDs.

Non-biologic. The most prominent non-biologic, methotrexate, is regarded as one of the most effective drugs in JIA treatment, superior to the other options listed including the biologic DMARDs. Its mechanism of action is unknown. Methotrexate is considered a cytotoxic drug (cell killing) and should be used cautiously. The medication is effectively used to stop or reduce progression of the condition which may provide long-term advantages over other treatment options.

Biologic DMARDs act by inhibiting TNFalpha, a protein playing an important role in immune functions. However, it also plays a role in cancer prevention, which may be why these drugs are associated with a slightly increased risk of lymphoma development. Their efficacy depends on the subtype of JIA (or type of autoimmune mechanism) concerned. A review of the research on these indicates that they are most effective in polyarthritis, and may have potential in cases of psoriatic and enthesitis-related JIA. Biologic DMARD types include:

  • Abatacept: This drug modulates the action of T-cells (an important component of the immune system) and may be suitable in cases where other DMARDs have failed. A six-month discontinuation trial of 60 patients with either systemic, oligoarthritic or polyarthritic JIA found that abatacept had a statistically significant reduction in flares in comparison with 62 patients on a placebo. Currently the Australian Pharmaceutical Benefits Scheme does not subsidise the cost of this medication for Juvenile Idiopathic Arthritis, and subsequently can be an expensive treatment.
  • Tocilizumab: This is an interleukin-6 receptor blocker, which may be suitable for treatment-resistant JIA. A trial randomising 20 patients to this drug and 23 to placebo found that symptom scores and biological inflammation markers were significantly reduced in the tocilizumab groups only. This medication is available on the PBS following authorisation according to stringent criteria. 

The following biologic DMARDs are TNFalpha inhibitors with good-quality trial evidence:

  • Adalimumab: A randomised discontinuation trial comparing adalimumab with methotrexate, adalimumab alone and placebo, showed that adalimumab alone reduced flares and symptom score significantly in comparison with the other groups.
  • Etanercept: This is a TNF receptor blocker. A double-blind trial of 51 polyarthritic JIA patients found that those randomised to etanercept had significantly fewer flares than the 25 on placebo. Another trial, albeit with only 7 receiving etanercept and 5 receiving a placebo, reported no significant effects on JIA symptoms.

Biologic DMARDs are also increasingly regarded as a first-line treatment, as an alternative to NSAIDs.

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References

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Ruperto N, Lovell DJ, Quartier P, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet.2008;372(9636):383-391.

Yokota S, Imagawa T, Mori M, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet.2008;371(9617):998-1006.

Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. The New England journal of medicine.2008;359(8):810-820.

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