Practice points
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The aim is to eliminate active arthritis in order to prevent permanent damage.
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Regular NSAIDs can be prescribed prior to the
Occasional reviewThe principles of pharmacological treatment of juvenile idiopathic arthritis
Introduction
Juvenile idiopathic arthritis (JIA) is one of the most common paediatric rheumatological diseases in the United Kingdom with an annual incidence of 1/10,000 children. It is defined as arthritis of unknown aetiology, persisting longer than 6 weeks, with an onset before the age of 16 years.
The pharmacological management of JIA is a rapidly progressing field. In addition to long established drugs, including methotrexate, there are new and innovative biological therapies which have revolutionized the care of children with rheumatic diseases. Despite these advances in therapy, a significant proportion of affected children continue to suffer disability secondary to active disease. A good understanding of the various pharmacological treatment options enables more effective treatment.
Section snippets
Treatment objectives
The key aim of drug treatment is to achieve control of active arthritis and to enable a normal quality of life for the child. The ultimate objective is to prevent the irreversible joint and organ damage that active arthritis can cause. The possible implications of untreated or inadequately treated disease include impaired growth, significant disability, visual loss from complications of uveitis and an impact on the child’s psychosocial development.
Management of JIA may necessitate treatment for
Outcome measures for assessing disease activity in JIA
A key to assessing response to treatment is having validated measures to disease activity. Originally developed to facilitate clinical trials, the American College of Rheumatology (ACR) Paediatric measures are used in routine clinical care to help assess efficacy of therapies.
The core set of outcome measures for JIA are:
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Physician global assessment of disease activity (10 cm visual analogue scale)
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Patient/parent assessment of overall well-being (10 cm visual analogue scale)
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Number of joints with
Therapeutic approaches
The International League Against Rheumatology (ILAR) has subdivided JIA into six subtypes (Table 1). Therapy and prognosis of each subtype varies.
The American College of Rheumatology (ACR) has recently published recommendations for the treatment of JIA, which cover the initiation and safety monitoring of the therapeutic agents used. These recommendations divide JIA into “five treatment groups”, instead of the ILAR JIA categories. Features of poor prognosis and disease activity, which are
Stepwise pharmacological treatment using the ACR 2011 recommendations
The exact timing and factors leading to the progression from one JIA medication to the next are not strictly defined. The recently published ACR 2011 recommendations, although not universally adopted, provide a framework of when to progress through the steps. The initial two steps in the pharmacological treatment of JIA are usually NSAIDs and intra-articular steroid injections, which may be repeated as required.
Patients with four or fewer joints involved may not require methotrexate at
Non-steroidal inflammatory drugs (NSAIDs)
NSAIDs have an analgesic and anti-inflammatory effect. They inhibit cyclooxygenase and thus reduce prostaglandins. Prostaglandins amplify the physiological mechanisms of pain and mediate the vasodilation of inflammation.
NSAIDs are suitable for most children from the onset of symptoms, prior to JIA being diagnosed. NSAIDs may sometimes be used as JIA monotherapy, but only for about 8 weeks, and usually only for children with less than four joints involved, low disease activity and no predictors
Methotrexate
Methotrexate is an antimetabolite, which acts by the inhibition of dihydrofolate reductase and other enzymes and thereby decreases production of purine nucleotides and thymidylate, which in turn are essential for DNA synthesis and cell division.
Methotrexate is the DMARD of choice for JIA. It is given once weekly, in doses ranging from 10 to 15 mg/m2, either orally or subcutaneously. The subcutaneous route provides greater bioavailability. Methotrexate can take 8 weeks to have a beneficial
Biologics
Biologics are newer treatments that target cytokines or the regulation of T or B cells. They have dramatically improved the treatment of JIA. Concern and vigilance over potential serious side effects is required. They may increase infection and there is a theoretical risk of malignancy. Only one biologic is used at a time. They should be avoided when there is active infection, current or previous untreated tuberculosis, malignancy, pre-malignancy state, immunodeficiency, pregnancy or
Ciclosporin
Ciclosporin inhibits T-cell activation and reduces the production of cytokines IL-2, IL-3, IL-4, and IFNγ. Ciclosporin is used infrequently in JIA. It is used in addition with other immunosuppressants when there has been an inadequate response, and in cases of HLH associated JIA. It is nephrotoxic. Side effects include hypertrichosis, hypertension, gingival hypertrophy, headache, fatigue and muscle cramps, renal and hepatic dysfunction. Blood levels should be measured to ensure that they are
Summary
There are a wide variety of pharmacological treatments for JIA as described above. These treatments are usually required for many years as the disease follows its relapsing course. Further studies on the aetiology of JIA and how to improve the long-term outcome of JIA are needed in order to fully utilize the medications and prevent permanent joint damage.
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