Page 758 - Clinical Immunology_ Principles and Practice ( PDFDrive )

730 Part six Systemic Immune Diseases

TABLE 53.2 Biological therapeutic agents Used in the treatment of Juvenile idiopathic
arthritis (Jia)
Frequency of
Biological target Name structure administration route of administration
Tumor necrosis Etanercept TNF receptor-immunoglobulin G Twice weekly to weekly Subcutaneous (SQ) injection
factor (TNF) (IgG) fusion protein
Infliximab Monoclonal antibody (chimeric) Every 4–8 weeks Intravenous (IV) infusion
Adalimumab Monoclonal antibody (humanized) Every 1–2 weeks SQ injection
Golimumab Monoclonal antibody (humanized) Every 4 weeks SQ injection
Every 8 weeks IV infusion
Certolizumab pegol Monoclonal antibody (humanized Every 2 weeks SQ injection
and PEGylated)
CD80/86 Abatacept Cytotoxic T lymphocyte antigen-4 Every 4 weeks IV infusion SQ injection
(CTLA-4–IgG fusion protein Weekly
Interleukin-1 (IL-1) Anakinra Receptor antagonist Daily SQ injection
Canakinumab Monoclonal antibody (humanized) Every 8 weeks SQ injection
Rilonacept Receptor-fusion protein Weekly SQ injection
IL-6 receptor Tocilizumab Monoclonal antibody (humanized) Every 2–4 weeks IV infusion SQ injection
Every 1–2 weeks
+
CD20 B cells Rituximab Monoclonal antibody 2 infusions 2 weeks apart, IV infusion
repeat every 6 months
IL-12 and IL-23 Ustekinumab Monoclonal antibody Every 12 weeks SQ injection
IL-17A Secukinumab Monoclonal antibody Every 4 weeks SQ injection

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by the 2011 ACR Recommendations for JIA treatment. As our form the foundation of therapy for children with mild or limited
knowledge about pathophysiology and response to treatment oligoarthritis. In addition, intraarticular injections may be effective
continues to expand, differential therapeutic approaches for the in children with more extensive arthritis and in those who are
disparate JIA phenotypes are eagerly anticipated. receiving concurrent systemic therapy. Randomized trials have
shown unequivocally that injected triamcinolone hexacetonide
Nonsteroidal Antiinflammatory Drugs has the longest duration of effect. 26
NSAIDs formed the foundation of the treatment of JIA for JIA also may be effectively treated with systemic glucocorti-
decades, and numerous NSAIDs have been shown to have coids. They are frequently used in the treatment of systemic
beneficial effects. In the absence of significant numbers of head- features of JIA and may form the foundation of the treatment
to-head trials, it is believed that in general all NSAIDs are similarly for the sJIA category, although biological therapies may signifi-
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1
effective, although indomethacin is considered by some to be cantly lessen the need for this practice. The use of systemic
the most effective NSAID (especially in sJIA). One NSAID may glucocorticoids for the treatment of synovitis in children with
be found to be more effective than another for a particular JIA is not an uncommon practice. However, the risks, benefits,
individual child. and appropriate use of this approach are less clear. The recent
In general, NSAIDs are not considered to be disease-modifying 2011 ACR Recommendations for JIA treatment do not include
agents, that is, they are not felt to slow the progression of disease this use of systemic glucocorticoids because of the near-complete
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or prevent the appearance of radiographic damage. For this absence of any published evidence. In general, most pediatric
reason, monotherapy with NSAIDs initially began to decline rheumatologists would agree that the use of DMARDs is preferable
with the advent of agents, such as methotrexate, that have been to the use of moderate-dose or high-dose systemic glucocorticoids
shown to modify the disease process. NSAIDs are frequently for the treatment of synovitis in JIA. The anticipated adverse
used for symptomatic relief, but most children who require daily effects of long-term use of moderate doses of glucocorticoids
chronic use of NSAIDs would likely benefit from the addition includes growth failure, osteoporosis, cataract formation, glau-
of systemic immunosuppression, such as from DMARDs. coma, hyperglycemia, hypertension, avascular necrosis of bone,
Gastrointestinal (GI) discomfort is a frequent adverse effect of striae, and others. 26
NSAID therapy, although frank GI bleeding appears to occur at
a lower incidence than in adults. Scarring pseudoporphyria of Nonbiological DMARDs
sun-exposed skin is another risk associated with NSAID use. The use of DMARDs was introduced in the 1980s (Chapter 87).
The long-term cardiovascular effects of NSAIDs in children have The most widely used and studied is methotrexate, which has
not been studied. been shown in randomized clinical trials to be efficacious in
1
treatment of JIA. Following these studies, methotrexate became
Glucocorticoids the cornerstone of therapy for many children with JIA. Methotrex-
Similar to many rheumatological diseases, JIA has been shown ate is typically administered weekly through either the oral or
to respond to treatment with glucocorticoids (Chapter 86). the subcutaneous route, although studies have shown subcutane-
Intraarticular glucocorticoid injections typically result in a ous methotrexate to be better absorbed and more effective. 1
near-immediate decrease in inflammation that is maintained Methotrexate may be associated with several typically
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for many months. Accordingly, intraarticular injections may minor adverse effects, such as nausea and fatigue. Occasionally,