MEDICAL AND SURGICAL TREATMENTS OF JIA
Children with JIA are treated with more of an induction and maintenance approach, taking advantage of windows of opportunity to modify the disease course, usually under the guidance of a pediatric rheumatologist (118). Treatment is aimed at inducing remission with the least medication toxicity. In 2011 and 2013, the ACR published recommendations for the treatment of JIA organized into five treatment groups as previously discussed (93,94). Within the five treatment groups, treatment is stratified into three disease activity levels (low, moderate, and high). Choice of treatment is guided by disease severity and the presence or absence of poor prognostic features.
In the first treatment group, history of arthritis in four or fewer joints, escalation of therapy typically proceeds from nonsteroidal anti-inflammatory drugs (NSAIDs) to intra-articular glucocorticoid injections to methotrexate to TNF-a inhibitors. In children with low disease activity (single joint, normal inflammatory markers, etc.), monotherapy with NSAIDs may be sufficient. Intra-articular injections of triamcinolone should provide relief for at least 4 months, and can be repeated if helpful. Methotrexate should be started as initial treatment in children with high disease activity and features of poor prognosis, or in those with lower disease activity who fail to show adequate response with NSAIDS and triamcinolone injections. In enthesitis-related JIA, sulfasalazine rather than methotrexate is recommended at a similar stage. After 3 to 6 months (depending on disease activity) of methotrexate with inadequate response, TNF-a inhibitor treatment should be considered.
In children with a history of arthritis in five or more joints (does not require five currently active joints), treatment with initial NSAIDs is more quickly escalated to methotrexate, with joint injection as needed. In moderate disease activity and poor prognostic features, or in children with high disease activity, treatment may start with methotrexate. Leflunomide is sometimes used as an alternative to methotrexate. The IL-6 inhibitor, tocilizumab, is now FDA-approved in children above 2 years of age and older with active polyarticular JIA (119). Tocilizumab can be used alone or in combination with methotrexate (120). Escalation to a TNF-a inhibitor follows in 3 to 6 months dependent on disease characteristics and severity if there is inadequate response to methotrexate or leflunomide.
If there is still no response with a TNF-a inhibitor after 3 to 4 months, another TNF-a inhibitor can be tried, or abatacept (a T cell inhibitor). Rituximab may be used for nonresponders to the previously mentioned regimen in those children with RF-positive polyarticular JIA.
In children with the third treatment group, active sacroiliac arthritis, use of a TNF-a inhibitor is recommended more readily than in any other treatment group. A TNF-a inhibitor may be started after failure of an adequate trial of NSAIDs or methotrexate or sulfasalazine for 3 to 6 months (depending on disease characteristics and severity).
In the 2013 recommendations, systemic JIA was broken down into three phenotypes: significant systemic features and varying degrees of synovitis, significant arthritis and no significant systemic features, and features concerning MAS (94,121). In children with significant systemic features and varying degrees of synovitis, initial treatment with anakinra (an interleukin 1 receptor inhibitor) or corticosteroids was recommended in most cases. For children without systemic features and with varying degrees of active synovitis, initial treatment recommendations were methotrexate or leflunomide for an active joint count higher than 4, with change to abatacept, anakinra, a tumor necrosis factor a inhibitor, or tocilizumab (120,106) if there is inadequate response. The interleukin 1 p inhibitor, canakinumab, has also been FDA-approved for systemic JIA (122). NSAIDS or intra-articular triamcinolone joint injections were recommended as initial treatment for children with four or less active joints (106).
For children with MAS, which carries an estimated 6% or more mortality rate, initial treatment recommendations include anakinra, a calcineurin inhibitor, or systemic glucocorticoid monotherapy for up to 2 weeks. The use of abatacept, intravenous immunoglobulin, or tumor necrosis factor a inhibitors is inappropriate for children with MAS (94,121).
It is stressed that systemic JIA is a very different disease from polyarticular JIA and that children need to be treated aggressively with biologies right away. Moving up to the next step after 1 month of inadequate response is recommended (121). The reader is encouraged to check the ACR website, rheumatology.org, for the most current, detailed recommendations for treatment of JIA.
Early and aggressive treatment of JIA with newer agents holds unlimited promise for even better outcomes for children with JIA. Steroids are used as sparingly as possible to control inflammation in order to avoid long-term side effects such as weight gain, poor growth, and risk of infection. There is no systemic evidence that steroids are disease-modifying (100).
Children with JIA are at high risk of developing osteopenia secondary to the disease itself, to steroid treatment of the primary disease, lack of physical activity and weight-bearing, limited sunshine exposure, and inadequate vitamin D and calcium. Calcium and vitamin D supplementation, sunshine, and encouragement of physical activity should be incorporated into the treatment plan.
Surgery is rarely used in the early course of the disease; however, surgery can be used later in the course to relieve pain, release joint contractures, and replace a damaged joint. Older children whose growth is complete or almost complete and whose joints are badly damaged by arthritis may need joint replacement surgery to reduce pain and improve function. Soft tissue releases may be needed to reposition malaligned joints or release contractures.