A significant number of patients with juvenile idiopathic arthritis (JIA) who stop taking Enbrel (etanercept) experience relapses. This happens more frequently in males and in patients with antinuclear antibodies and higher levels of C-reactive protein, researchers found.
Their study, “Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor-negative Juvenile Idiopathic Arthritis Who Reached Remission while Taking Medication,” was published in The Journal of Rheumatology.
JIA is the most common rheumatic condition in children and one of the leading causes of short- and long-term disability. The first-line treatment for children with JIA is generally nonsteroidal anti-inflammatory drugs (NSAIDS), glucocorticoids, or disease-modifying anti-rheumatic drugs (DMARDs).
Among DMARDs, methotrexate (MTX) is the most commonly used, but studies have shown that MTX doesn’t work for everyone.
A class of drugs called tumor necrosis factor (TNF) inhibitors has been found to be effective in patients with JIA who do not respond to methotrexate. Enbrel (marketed by Amgen) is the first TNF blocker approved for the treatment of polyarticular JIA.
The number of children treated with Enbrel has increased significantly in recent years, and many of these young patients achieve long-term remission. But little is known about the risk of flares (relapses) after they stop taking Enbrel, called “withdrawal” from the therapy.
Researchers from the Baby Jesus Pediatric Hospital in Rome, Italy, set out to evaluate the rate of disease flares, or relapses, after Enbrel withdrawal in 110 JIA patients (median age at disease onset was 3.6 years) who were treated with the therapy for at least 18 months, and who achieved and maintained a clinically inactive disease (CID) state for at least six months during treatment.
Patients were followed for 12 months after Enbrel withdrawal.
Researchers found that 60% of patients (66 out of 110) had an arthritis flare after they stopped taking Enbrel. Among the 66 patients who had relapses, 10% (seven patients) had concurrent anterior uveitis (inflammation of the middle layer of the eye).
The median time to flare was 4.3 months. The number and type of joints involved at baseline (before the study began) were not associated with flare rates.
When evaluating risk factors, a statistical analysis showed that patients with more frequent flares tended to be males, had positive anti-nuclear antibodies (ANA) and higher values of C-reactive protein (CRP, a marker of inflammation) at baseline.
But these three risk factors carried little weight with researchers when it came down to the clinical level — doctors treating patients and making therapeutic decisions.
“Our results show that a significant proportion of patients with JIA who maintain CID for at least 6 months experience a relapse after [Enbrel] withdrawal,” researchers wrote.
“Albeit significantly associated with flare, we conclude that male sex, ANA positivity, and elevated CRP are variables of little relevance in clinical practice for guiding therapeutic decisions,” they added.