Using conventional treatment strategies is an effective approach in most children with juvenile arthritis (JIA) and is still recommended as a first-line strategy, according to a population-based study in Canada.
The research, “Real-World Effectiveness of Common Treatment Strategies for Juvenile Idiopathic Arthritis: Results from a Canadian Cohort,” appeared in the journal Arthritis Care & Research.
The effectiveness of conventional JIA therapies may be undervalued because of the recent emphasis on biologic medications, such as etanercept (sold as Enbrel and others), adalimumab (Humira and Cyltezo, among others), golimumab (Simponi), abatacept (Orencia), tocilizumab (Actemra), or infliximab (sold as Remicade and others).
Although the 2011 American College of Rheumatology (ACR) recommendations for the treatment of JIA include non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injections — with or without the immunosuppressant methotrexate, depending the number of joints involved — the efficacy of this strategy in clinical practice remains scarcely understood.
Aiming to address this gap, the team used data from a nationwide group of JIA patients to evaluate the effectiveness of common treatments and find variables associated with therapeutic benefit in JIA.
Children with JIA were recruited at 16 Canadian centers between 2005 and 2010 as part of the ReACCh-Out study, and were followed for up to five years. Study visits were conducted at enrollment and at 6, 12, 18, 24, 36, 48, and 60 months. Among the collected data were the patients’ clinical information, JIA categories, levels of inflammatory markers, and medications used.
Treatment success was defined as achieving inactive disease — including no active joints (swollen or with limited movement with pain or tenderness) and no active extra-articular manifestations — or maintaining this state for a minimum of six months when stepping down treatment. Minimally active disease was an acceptable criterion for patients with a polyarticular course.
The analysis involved 1,352 children with JIA (855 females), who were assessed in a total of 14,350 visits. Median age at JIA onset was 8.5 years, while the median follow-up duration was 35.5 months.
The median duration of a treatment trial — meaning a period with stable treatment and standardized clinical assessments — was 7.4 months. Further analysis revealed that 2,740 treatment trials were so-called step-up trials (when therapy was added), 1,364 were step-down (treatment discontinuation), and 320 involved replacing one therapy for another in the same class. Five trials could not be categorized.
The success rate for the overall 4,429 treatment trials was 58.9%. Across all step-up treatments, the success was 58.8% for initial trials (within two months of diagnosis), 61.6% for early trials (within 2-12 months of diagnosis), and 54.5% for late trials (those performed more than 12 months after diagnosis).
Among step-up trials, 697 were of standalone treatment with NSAIDs in 587 patients. The most frequently used NSAID was naproxen (84.2%) and most of these treatment periods involved patients with oligoarthritis (52.2%) — the name given to arthritis diagnosed in children through age 16.
The success rate for NSAIDs was 54.4%. It was higher when the active joint (those affected) count was less than five (59.5%) and lower when it was more than five (27.4%). The median duration for successful trials was 10.1 months.
NSAIDS were combined with intra-articular corticosteroids in 370 patients, most commonly naproxen with triamcinolone via injection (80.3%). As with stand-alone NSAIDS, the majority of these trials involved patients with oligoarthritis (66.2%). The success rate was 64.7%; the median duration of successful trials was 7.1 months.
Methotrexate was used in 419 patients, mostly in children who had failed NSAID or as initial treatment for those with five or more active joints. The overall success rate was 60.5%; higher in children with less than five active joints initially. The median duration of successful trials was 11.5 months.
In turn, the success rate when combining methotrexate and prednisone was 57.4%, while that of treatments with sulfasalazine with or without NSAID or joint injections was 57.7%.
Adding a biologic medication such as etanercept led to a 62.0% success rate in 129 trials, while adding infliximab resulted in a lower success rate (50%) in 36 trials. Other biologics were also used in fewer trials.
The data further revealed that a higher number of active joints, ankle involvement and undifferentiated JIA were significantly associated with lower success of treatment with NSAIDS with or without joint injections.
Success with methotrexate with or without NSAIDs and joint injections correlated with a lower number of active joints and number of years since disease onset, as well as no involvement of the cervical spine.
As for step-down trials, 882 (64.7%) started when the patient met the criteria for inactive disease. Most commonly, they involved stopping NSAID monotherapy (73.4% success) and stepping down from a combination of methotrexate with an NSAID to standalone methotrexate therapy (74.0% success).
Overall, “these real-world effectiveness estimates show [that] conventional non-biologic treatment strategies recommended in current guidelines are effective in achieving treatment targets in many children with JIA,” the scientists said. “They remain a reasonable approach to initial treatment for most patients.”
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