Disease Duration, Category May Help Predict Response to Enbrel in Juvenile Idiopathic Arthritis Patients

Disease Duration, Category May Help Predict Response to Enbrel in Juvenile Idiopathic Arthritis Patients

The category and duration of disease in juvenile idiopathic arthritis (JIA) could help predict whether treatment with Enbrel (etanercept) in patients without systemic manifestations will be effective, a new study from Russia shows.

The study, “Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children’s Health, Russia,” was published in the Pediatric Rheumatology Online Journal.

The research was led by Ekaterina I. Alexeeva, from the National Scientific and Practical Center of Children’s Health at Russia’s Health Ministry in Moscow.

JIA is divided into seven categories, each with specific recommendations for initial treatment and guidelines for switching medications if they fail or if serious adverse effects occur.

Because the disease often progresses after treatment with conventional therapies, scientists have been searching for new treatments and ways to predict the disease.

Enbrel, marketed by Amgen, is an inhibitor of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). The drug has shown effectiveness in several studies, but in many cases, it has failed to reduce disease activity and lead to clinical remission.

Several factors associated with a better response to Enbrel in JIA have been identified, including younger age at disease onset, shorter disease duration, non-systemic disease onset, lower disability at the start of therapy, and reduced use of disease-modifying antirheumatic drugs (DMARDs).

However, the data have not been consistent, making reliable development of predictors for Enbrel treatment difficult.

The team led by Alexeeva conducted a study to determine Enbrel’s effectiveness and to identify predictors of response to treatment within 12 months in patients with JIA without systemic manifestations.

The study included 197 juvenile patients from Russia, who used Enbrel from 2009 to 2014. Response to therapy was evaluated using criteria from the American College of Rheumatology (ACRPedi 30/50/70/90, meaning at least 30%, 50%, 70%, or 90% improvement in three or more variables of JIA), and other standardized criteria, such as the Wallace criteria and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71).

Potential factors associated with response to treatment were assessed in different JIA categories.

Results showed that 179 (90.9%) of the patients achieved ACRPedi30; 177 (89.8%) achieved ACRPedi50; 168 (85.3%) achieved ACRPedi70; and 135 (68.5%) achieved ACRPedi90 response after one year.

Excellent response to Enbrel — meaning achieving ACRPedi90 and clinically inactive disease, according to both the Wallace criteria and JADAS-71 — was found in almost half (45.7%) of patients and was associated with persistent oligoarticular JIA, generally the mildest form of the disease, as well as shorter disease duration (up to two years), lower number of DMARDs before the start of Enbrel treatment, a decreased number of joints with limited motion, and lower C-reactive protein at baseline, an indicator of inflammation.

In contrast, a poor response to Enbrel treatment (failure to achieve ACR 70 or inactive disease according to both the Wallace criteria and JADAS-71) was associated with the polyarticular (more than four affected joints during the first six months of disease) or enthesitis-related JIA categories (clinically heterogeneous, accounting for 10-20% of JIA cases), higher disease duration before treatment with Enbrel, and older age at disease onset.

Among the study’s limitations, the authors mentioned the lack of a control group, which prevented them from assessing the predictors as prognostic markers and the potentially greater effectiveness of a different treatment for poor responders.

Overall, the findings “demonstrated that the response to etanercept therapy was strongly associated with the JIA category,” the authors wrote. The response was also associated with disease duration before the start of Enbrel treatment.

“These factors may help physicians to identify patients who might benefit from earlier treatment with etanercept,” the team concluded.

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