Which medications in the drug class Immunomodulators are used in the treatment of Juvenile Idiopathic Arthritis?

Updated: Jul 25, 2019
  • Author: David D Sherry, MD; Chief Editor: Lawrence K Jung, MD  more...
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Answer

Immunomodulators

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. [41]

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. [46]

Adalimumab (Amjevita, Cyltezo, Humira, Hadlima, Hyrimoz, Adalimumab-atto, Adalimumab-adbm, Adalimumab-bwwd, Adalimumab-adaz)

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 Humira. FDA approved adalimumab-atto, adalimumab-adbm, adalimumab-adaz, adalimumab-bwwd for patients 4 years or older, as biosimilars and not as interchangeable drugs.

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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