Page 759 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 53 Juvenile Idiopathic Arthritis 731

methotrexate may cause liver toxicity, necessitating periodic
measurement of serum aminotransferase levels for routine Treatment of Oligoarthritis (Arthritis of ≤4 Joints)
monitoring. Because of fewer involved joints, oligoarthritis may generally be
Leflunomide has been shown to be slightly less efficacious viewed as a milder form of JIA. However, significant disability
1
than methotrexate in the treatment of JIA. It may serve as an can still occur, and children with this condition should not be
alternative therapy for children who are intolerant of methotrex- assumed to have had good clinical outcomes without proper
ate. Sulfasalazine is used, to varying degrees, by pediatric evaluation and therapy. The foundation of treatment for this
rheumatologists and may be of particular benefit to children JIA phenotype is intraarticular glucocorticoid injections. These
1
with JIA of the ERA category. Hydroxychloroquine monotherapy injections may be administered in multiple joints concurrently
28
has been demonstrated inefficacious in treating JIA. 1 and may be repeated, as needed. A good response typically
results in resolution of clinical signs and symptoms of arthritis
Biological DMARDs for 4–12 months. DMARD therapy should be initiated in children
The use of biological DMARDs for the treatment of JIA began who do not respond as desired to injections or who have more
24
in the late 1990s (Chapter 89). Etanercept, a TNF inhibitor, was significant arthritis. Methotrexate is typically the agent of first
the first studied and was shown to be efficacious in a randomized choice. Significant arthritis that does not respond adequately to
1
clinical trial. Additional TNF inhibitors have been introduced methotrexate can be treated with TNF inhibitors. 24
and used in the treatment of JIA; adalimumab was also shown
1
to be efficacious in a randomized clinical trial. Notable dif- Treatment of Polyarthritis (Arthritis of ≥5 Joints)
ferences have been discovered regarding the effectiveness of Methotrexate is currently recommended for nearly all children
24
the TNF receptor fusion protein (etanercept) and the mAbs with polyarthritis. If a brief trial of methotrexate proves
(adalimumab, infliximab, and others). mAb TNF inhibitors have inadequate to control the arthritis, then TNF inhibitors are
24
been shown to be effective against two important JIA-associated frequently recommended. If an adequate response to the initial
conditions—anterior uveitis and IBD. Receptor fusion proteins TNF inhibitor is not seen, then switching to another of the TNF
24
have been shown to be far less effective in treating these condi- inhibitors or switching to abatacept is currently recommended.
tions. The precise mechanism for these differences in treatment The most appropriate role of other effective biological DMARDs,
effectiveness is not clear but may be related to the ability of such as tocilizumab (see Table 53.2), in the treatment of poly-
etanercept to bind lymphotoxin or the ability to bind surface articular JIA has yet to be clearly defined.
membrane-bound TNF. 29
Because the TNF inhibitors are large proteins, they must be Treatment of Arthritis Involving Specific Joints
administered parenterally, either by subcutaneous injection or Arthritis involving the TMJ, hip, and sacroiliac joints may deserve
intravenous infusion (see Table 53.2). TNF inhibitors are not special therapy. Destructive arthritis of the TMJ among children
generally associated with common medication adverse effects, with JIA has been noted for decades. Clinical evaluation of this
such as headache or nausea, although they may result in injection joint is particularly challenging, as symptoms are often absent
site or infusion reactions. There appears to be a modest increase initially, and physical examination findings may be normal.
in the incidence of bacterial infections associated with TNF Accordingly, the optimal treatment for TMJ arthritis is unclear.
30
inhibitor use and a significant risk of reactivation of latent Many authors recommend targeted therapy with intraarticular
29
tuberculosis. Therefore individuals should be screened for glucocorticoid injections, similar to the treatment of arthritis
2
tuberculosis infection prior to initiating treatment with TNF in other joints. Increased systemic therapy is likely also appropri-
24
inhibitors. The possible association between TNF inhibitors ate, although TMJ arthritis has been known to demonstrate
and an increased rate of malignancy in JIA remains an open radiographic progression despite treatment with systemic TNF
question; however, currently, there is no convincing evidence of inhibitors and in the absence of signs of active synovitis of other
a strong increased risk of overall malignancy. 31 joints. 2,22
In addition to TNF inhibitors, the T-cell costimulation The presence of hip arthritis in JIA has been shown in
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modulator abatacept has been shown in a randomized clinical several studies to portend a poor prognosis. Accordingly, many
1
trial to be efficacious in the treatment of JIA. Presumably, because authors advocate early intraarticular glucocorticoid injections
of the effectiveness of TNF inhibitors, the use of abatacept has and increased systemic therapy when active hip arthritis is
remained relatively limited in clinical practice. identified.
The B-cell–depleting agent rituximab has been minimally Sacroiliac arthritis is strongly associated with the development
1
studied in the treatment of JIA. However, it appears effective in of ankylosing spondylitis. Because axial arthritis has been shown
some instances, particularly in children who appear to have early- to be less responsive to methotrexate therapy, current recom-
+
onset RA (teenagers with RF and CCP-positive polyarthritis). mendations suggest a lower threshold for the initiation of TNF
24
The IL-1 inhibitor anakinra has been shown in both inhibitors when sacroiliac arthritis is present. However, early
uncontrolled and controlled studies to be particularly effective treatment with TNF inhibitors, or perhaps even newer biological
in the treatment of sJIA. 1,25 Similar to the experience in adults agents that inhibit IL-17 or IL-12/IL-23, may be optimal for the
with RA, anakinra appears less effective in treating synovitis treatment of spondyloarthritis to help prevent progression of
among children with the other categories of JIA. Additional ankylosis in children. 27
IL-1 inhibitors (rilonacept, canakinumab) are also now com-
mercially available and have been shown beneficial in clinical trials Treatment of Erosive Arthritis
treating sJIA. 1 It appears that not all children with JIA have the propensity to
Unlike other biological agents, the IL-6 inhibitor tocilizumab develop an erosive arthritis that is similar to that frequently seen
has been shown in randomized clinical trials to be efficacious in adults with RA. Children who develop erosions visualized on
in the treatment of both sJIA and polyarticular JIA. 1 plain radiographs are considered to have a worse prognosis, and