Is Long-term Etanercept Therapy Safe and Effective in Patients With Juvenile Rheumatoid Arthritis?

Raphael Hirsch

Disclosures

Nat Clin Pract Rheumatol. 2008;4(12):628-629. 

Practice Point

In children with juvenile rheumatoid arthritis who show continued response to etanercept, the drug can be given safely for at least 8 years.

Summary

Traditional treatment for juvenile rheumatoid arthritis (JRA) includes the use of NSAIDs, corticosteroids, and DMARDs such as methotrexate; however, these drugs are not effective in all patients. Although the use of tumor necrosis factor inhibitors has dramatically improved outcomes in patients with JRA, the long-term safety of these agents in children remains a concern. Lovell et al. recently reported the long-term follow-up of a randomized controlled trial that had shown in 69 patients that etanercept was effective in the treatment of JRA. In the 8-year, open-label extension study (n = 58), the drug remained well tolerated and few adverse events were reported. These results indicate that a substantial number of patients with JRA will have a sustained response to etanercept and that the drug can be given safely for at least 8 years. Although the patients in this study were diagnosed with polyarticular JRA according to American College of Rheumatology criteria, it is reasonable to generalize the findings to patients with polyarticular juvenile idiopathic arthritis as defined by the International League of Associations for Rheumatology guidelines.

Commentary

Juvenile rheumatoid arthritis (JRA) is the most common rheumatic disease seen in children. Traditional treatment options for JRA -- including NSAIDs, corticosteroids, and DMARDs such as methotrexate -- are not effective in all patients.[1,2]

In recent years, new drugs have been developed that target specific mediators of inflammation. One central target in many forms of arthritis is tumor necrosis factor (TNF). Etanercept was the first anti-TNF agent to show efficacy in a randomized, controlled trial in polyarticular JRA,[3] and the first to be approved for use in children. The use of anti-TNF agents has dramatically improved outcomes in patients with JRA; however, JRA is a chronic disease and most patients will require long-term medication. In a recent study by Wallace and colleagues of 437 patients with JRA who were followed up for at least 4 years, only 35% demonstrated a period of disease inactivity of at least 12 months while off medication.[4] Thus, it is likely that most patients with JRA will require treatment well into adulthood and possibly even for life. Unfortunately, the potential adverse effects of continuous exposure to anti-TNF agents on the growing child and over the course of decades are not known.

In this regard, the results of the recent study by Lovell et al. are reassuring.[5] The authors previously reported the long-term follow-up of a randomized control trial in which etanercept was shown to be effective for the treatment of polyarticular JRA in 69 patients diagnosed according to American College of Rheumatology (ACR) criteria.[3] The open-label extension study included 58 patients (84% of the original cohort) who continued to receive etanercept for up to 8 years.[5] The drug remained well tolerated, with just nine serious adverse events reported in four patients (7%) after more than 4 years of etanercept therapy. These adverse events included six cases of flare or worsening of disease and one case each of pyelonephritis, arthralgia and allergic reaction. In addition, there were no reported cases of tuberculosis, opportunistic infection or malignancy. This long-term safety profile is similar to that reported in studies of etanercept use in adult rheumatic disorders such as rheumatoid arthritis and ankylosing spondylitis.

In terms of efficacy, the current study revealed that many patients continue to do well on etanercept. An ACR Pediatric 70 response, or higher, was achieved in all 11 patients for whom 8 years of data were available; however, only 38% of the original 69 patients (n = 26), remained on etanercept therapy after 8 years. Three patients were lost to follow-up, but the remainder discontinued therapy for reasons that suggest a loss of efficacy, including suboptimum clinical response, refusal to continue taking the drug, and physician decision. Furthermore, 53% of patients had received one or more DMARD during the 8-year period of observation, suggesting that etanercept alone was not controlling their symptoms. The data as a whole suggest that etanercept's efficacy decreases over time in as many as half of all patients.

In summary, the study by Lovell and colleagues indicates that a substantial number of patients with JRA will have a sustained response to etanercept that can last many years. The drug was well tolerated and had a good safety profile over an 8-year period of observation. Although the patients in this study were diagnosed as having JRA according to ACR criteria, it is reasonable to generalize these findings to patients with polyarticular juvenile idiopathic arthritis as defined by the International League of Associations for Rheumatology guidelines.


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