The study, “Tofacitinib Treatment of Refractory Systemic Juvenile Idiopathic Arthritis,” was published in the journal Pediatrics.
Approximately 10% of juvenile arthritis cases in North America are children and adolescents with systemic JIA. This form of the disease is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (a type of steroid compound), or disease-modifying anti-rheumatic medicines such as Kineret (anakinra, marketed by Sobi) or Ilaris (canakinumab, marketed by Novartis).
However, such treatment regimens aren’t always effective, with nearly half of patients still having some symptoms of active disease. They also can trigger severe side effects or can be challenging to use in children.
Xeljanz is an orally available small molecule developed by Pfizer to inhibit a protein called janus-activated kinase (JAK), which plays a key role in the activation of pro-inflammatory cellular signals. It is currently approved for the treatment of moderate to severe rheumatoid arthritis in adults in both the U.S. and E.U., but its efficacy in pediatric patients is still being investigated.
A team led by Chinese researchers reported the case of a 13-year-old girl who had systemic JIA. She was first diagnosed at age 11 after complaints of persistent joint pain, a fever, and enlarged lymph nodes, detected by computed tomography (CT) imaging.
Although combined treatment with NSAIDs and glucocorticoids was able to reduce her symptoms, she continued to experience disease flares.
A new clinical evaluation confirmed the initial diagnosis of systemic JIA. After changing treatment combinations, her fever was resolved but her arthritis symptoms remained almost unchanged. Later on she developed vertebral compression fractures, probably due to osteoporosis resulting from chronic use of corticosteroids.
The clinicians initially suggested starting treatment with tocilizumab (sold as Actemra in the U.S. and RoActemra in the E.U.), an antibody that can block the activity of interleukin-6, one of the inflammatory molecules thought to drive arthritis. However, like many biologic therapies, tocilizumab must be injected, and the patient’s family refused treatment that couldn’t be taken orally.
Given this setback, she started off-label treatment with 2.5 mg of Xeljanz twice daily in addition to daily methylprednisolone.
“Remarkably, after experiencing chronic joint inflammation for nearly two years, her arthritis improved steadily over the next two months,” the researchers said.
Three months after starting treatment with Xeljanz, a new clinical evaluation and disease activity score assessment confirmed that she had achieved complete disease remission. Three months later she was able to stop taking corticosteroids for the first time since her initial diagnosis. However, she had a brief resurgence of joint swelling when there was a three-week interruption of Xeljanz.
In general, her symptoms were well-controlled while she was on this treatment regimen, with no toxicity or adverse events reported.
These positive results support the use of Xeljanz for the treatment of systemic JIA. Still, “the safety profile of long-term tofacitinib therapy in children is an important topic that warrants further study,” researchers said.