Juvenile Idiopathic Arthritis Medication

Updated: Oct 06, 2017
  • Author: David D Sherry, MD; Chief Editor: Lawrence K Jung, MD  more...
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Medication

Medication Summary

Optimal care of patients with juvenile idiopathic arthritis (JIA) requires an integrated approach of nonpharmacologic and pharmacologic therapies. Classes of medications used include disease-modifying antirheumatic drugs (DMARDs), biologicals, NSAIDs, and corticosteroids.

 

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Nonsteroidal Anti-inflammatory Drugs

Class Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) interfere with prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX), thus reducing swelling and pain. NSAIDs are used to treat all subtypes of JIA. They may help with pain and decrease swelling. Commonly used NSAIDs include naproxen, ibuprofen, tolmetin, diclofenac, and indomethacin.

Aspirin is no longer the drug of first choice because of the increased frequency of gastric toxicity and hepatotoxicity when compared to other NSAID medications. The cyclooxygenase 2 (COX-2) inhibitor celecoxib (Celebrex) may have a role in treatment when a bleeding diathesis is a potential problem.

Several dozen NSAIDs are available and can be classified into different groups of compounds. Commonly used NSAIDs include ibuprofen, naproxen, ketoprofen, piroxicam, and diclofenac. Predicting which patient will respond to a particular NSAID is not possible and many children who do not respond to one may benefit by changing to a different NSAID. Indomethacin is particularly effective for fever and pericarditis and is usually preferred for children with active systemic JIA.

Meloxicam (Mobic)

Meloxicam is a member of the enolic class of NSAIDs and is structurally related to piroxicam. The pediatric dosage is 0.125 mg/kg/d for patients aged 2 years or older, up to 7.5 mg qd.

Naproxen (Aleve, Naprelan, Naprosyn)

Naproxen is used for analgesic and anti-inflammatory properties, treating arthralgia and arthritis. It inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis. The pediatric dosage is 7-20 mg/kg/d PO divided bid/tid, not to exceed 1 g/d

Ibuprofen (Advil, Motrin)

Ibuprofen inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. The adult dosage is 400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist, not to exceed 3.2 g/d; the pediatric dosage is 30-50 mg/kg/d PO divided qid, not to exceed 2.4 g/d.

Diclofenac (Voltaren, Cataflam)

This is one of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. It is believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Diclofenac can cause hepatotoxicity; hence, liver enzymes should be monitored in the first 8 weeks of treatment. It is absorbed rapidly; metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. The delayed-release, enteric-coated form is diclofenac sodium, and the immediate-release form is diclofenac potassium.

Celecoxib (Celebrex)

Celecoxib inhibits primarily COX-2. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions, may be decreased when compared with nonselective NSAIDs.

Seek the lowest dose for each patient. The adult dosage is 100-200 mg PO bid; the pediatric dosage has not been established for patients younger than 2 years, is 50 mg PO bid for patients 2 years or older whose weight is ≥10 kg to ≤25 kg, and is 100 mg PO bid for patients 2 years or older whose weight is greater than 25 kg.

Tolmetin (Tolectin)

Tolmetin inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase, which in turn decreases formation of prostaglandin precursors. The pediatric dosage is 20 mg/kg/d PO divided tid/qid initially, then 15-30 mg/kg/d, not to exceed 30 mg/kg/d

Indomethacin (Indocin)

Indomethacin is rapidly absorbed, and metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. It inhibits prostaglandin synthesis. The adult dosage is 25-50 mg PO bid/tid, not to exceed 200 mg/d, and the ER product may be administered qd or bid; the pediatric dosage is 1-2 mg/kg/d PO divided bid/qid, not to exceed 4 mg/kg/d or 150-200 mg/d

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Disease-Modifying Antirheumatic Drugs

Class Summary

Disease-modifying antirheumatic drugs (DMARDs) can retard or prevent disease progression and, thus, joint destruction and subsequent loss of function. Successful DMARD therapy may eliminate the need for other anti-inflammatory or analgesic medications; however, until the full action of DMARDs takes effect, anti-inflammatory or analgesic medications may be required as bridging therapy to reduce pain and swelling.

Sulfasalazine (Azulfidine, EN-tabs)

Sulfasalazine decreases the inflammatory response and systemically inhibits prostaglandin synthesis. The pediatric dosage has not been established for patients younger than 6 years; for patients 6 years or older, the typical dose range is 30-50 mg/kg/d; to lessen GI irritation, start at one half to one third of maintenance dose, increasing the dose weekly, not to exceed 2 g/d.

Methotrexate (Rheumatrex, Trexall)

Methotrexate has an unknown mechanism of action in the treatment of inflammatory reactions; it may affect immune function. It ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust the dose gradually to attain a satisfactory response. Consider SC route for patients who do not respond to PO methotrexate or who have GI intolerance to PO dosing.

The pediatric dosage is 10-25 mg/m2/wk PO/IM/SC as a single dose or divided into 2 doses weekly; many pediatric rheumatologists increase the dose (not to exceed 30 mg/m2, approximately equivalent to 1 mg/kg); administer with folic acid 1-2 mg PO qd or folinic acid 2.5-5 mg PO qwk

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Corticosteroids

Class Summary

Corticosteroids are potent anti-inflammatory drugs used in patients with JIA to bridge the time until DMARDs are effective. Adverse events associated with long-term steroid use make dose reductions and cessation important in due course.

Methylprednisolone (Solu-Medrol, Medrol, A-Methapred)

Methylprednisolone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. It is used temporarily for JIA until longer-term treatment provides effective relief. The pediatric dosage is 15-30 mg/kg IV qd administered over 30-60 min for 2-3 d.

Prednisone

Prednisone is an immunosuppressant for treatment of JIA. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity, and it stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. The pediatric dosage is 4-5 mg/m2/d PO; alternatively, the dosage is 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve and other antirheumatic drugs take effect.

Triamcinolone (Aristospan, Kenalog)

Triamcinolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.

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Immunomodulators

Class Summary

The recognition of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)–1 as central proinflammatory cytokines has led to the development of agents that block these cytokines or their effects. In addition to improving signs and symptoms and quality of life, all biologic agents significantly retard radiographic progression of joint erosions. The TNF blockers, which bind TNF and thus prevent its interaction with its receptors, include etanercept, infliximab, and adalimumab. Consensus statements do not recommend their use until at least one xenobiotic DMARD, usually methotrexate (MTX), has been administered without sufficient success, although one study reported better results with etanercept in patients with less disability and when used before methotrexate. [40]

Adverse effects associated with the biologic agents include the generation of antibodies against these compounds, emergence of antinuclear antibodies, occasional drug-induced lupuslike syndromes, and infections. Rarely, demyelinating disorders and bone marrow suppression occur. Acute and chronic infections, demyelinating disorders, class 3 or 4 heart failure, and recent malignancies are contraindications for TNF blockers. Thoroughly searching for latent tuberculosis using chest radiography and/or purified protein derivative (PPD) testing is recommended before these agents are started. [44]

Adalimumab (Humira, Amjevita, adalimumab-atto)

Adalimumab is a recombinant human IgG1 monoclonal antibody that is specific for human TNF. It reduces inflammation and inhibits progression of structural damage. The pediatric dosage has not been established for patients younger than 2 years. For patients age 2 years or older and between 10 kg and just under 15 kg, the dosage is 10 mg SC q2wk; for 15 kg to just under 30 kg, the dosage is 20 mg SC q2wk; and for 30 kg or more, the dosage is 40 mg SC q2wk.

Etanercept (Enbrel)

Etanercept acts by binding and inhibiting TNF, a cytokine that contributes to inflammatory and immune response. The pediatric dosage is not established for patients younger than 4 years. For patients 4-17 years, the dosage is 0.4 mg/kg SC 2 times weekly (administered at least 72-96 h apart), not to exceed 25 mg/dose. For patients older than 17 years, the dosage is administered as in adults.

Abatacept (Orencia)

Abatacept is a selective costimulation modulator that inhibits T-cell activation by binding to CD80 and CED86, thereby blocking CD28 interaction. It is indicated for reducing signs and symptoms of RA, slowing progression of structural damage and improving physical function in adults with moderate-to-severe RA who have inadequate response to DMARDs, MTX, or TNF antagonists. It is not recommended for concomitant use with anakinra because of insufficient experience.

The pediatric dosage is not established for patients younger than 6 years. For pediatric patients 6-17 years, the dosage is according to body weight, and the drug is administered on days 1, 15, and 29, then q4wk thereafter; infuse IV over 30 min. For pediatric patients less than or equal to 74 kg, use 10 mg/kg IV; for pediatric patients 75-100 kg, use 750 mg IV; and for pediatric patients heavier than 100 kg, use 1000 mg IV.

Anakinra (Kineret)

Anakinra competitively and selectively inhibits IL-1 binding to type I receptor (IL-1RI). By blocking IL-1 binding, inflammation and pain associated with rheumatoid arthritis are inhibited. It is indicated for rheumatoid arthritis in patients who have failed 1 or more DMARDs. The dose should be administered at approximately the same time every day. The adult dosage is 100 mg SC qd; the pediatric dosage has not been established.

Tocilizumab (Actemra)

Tocilizumab is an IL-6 receptor antagonist that inhibits IL-6 mediated signaling that results in decreased inflammatory cytokine production. It is indicated for systemic JIA and PJIA. The safety and efficacy of tocilizumab has not been established in patients younger than 2 years old.

Canakinumab (Ilaris)

Canakinumab is recombinant, human monoclonal antibody that inhibits interleukin-beta1.

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