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Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondylarthropathy
Shirley M L Tse1, Ruben Burgos-Vargas, Ronald M Laxer
1Division of Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. shirley.tse@sickkids.ca
Insights
Anti-tumor necrosis factor alpha (TNFalpha) agents effectively treated refractory juvenile spondylarthropathy (SpA) in a 1-year study. Patients experienced significant improvements in arthritis and enthesitis, with reduced medication needs.
Area of Science:
- Pediatric rheumatology
- Immunology
- Inflammatory diseases
Background:
- Juvenile spondylarthropathy (SpA) presents persistent inflammation resistant to standard therapies.
- Tumor necrosis factor alpha (TNFalpha) is implicated in the pathogenesis of synovitis and enthesitis in juvenile SpA.
- Refractory cases lead to significant morbidity and reduced quality of life in affected children.
Purpose of the Study:
- To evaluate the efficacy of anti-TNFalpha agents in children with juvenile SpA.
- To assess the impact of these therapies on patients refractory to conventional treatments like NSAIDs, DMARDs, and corticosteroids.
Main Methods:
- A 1-year follow-up study involving ten HLA-B27 positive juvenile SpA patients (mean age 15.0 years).
- Patients received either infliximab (n=8) or etanercept (n=2).
- Outcomes measured included tender entheseal count (TEC), active joint count (AJC), inflammation markers, Childhood Health Assessment Questionnaire (C-HAQ) scores, and medication requirements.
Main Results:
- All patients showed resistance to multiple conventional therapies at baseline.
- Significant improvements in arthritis and enthesitis (remission of TEC and AJC) were observed by 6 months, sustained for 1 year.
- Inflammation markers and C-HAQ scores normalized, with a notable reduction in the need for other antirheumatic drugs.
Conclusions:
- Anti-TNFalpha therapy represents a promising novel treatment for refractory juvenile SpA.
- Further prospective research is warranted to confirm effectiveness and long-term outcomes in this patient population.
Objective:
Persistent inflammation refractory to standard antirheumatic therapy in children with juvenile spondylarthropathy (SpA) leads to morbidity and reduced quality of life. Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of synovitis and enthesitis. This study was undertaken to examine the impact of anti-TNFalpha agents on juvenile SpA that is refractory to nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs, and corticosteroids.
Methods:
Ten juvenile SpA patients with a mean +/- SEM age of 15.0 +/- 0.7 years and disease duration of 4.4 +/- 0.8 years, all of whom were HLA-B27 positive, were followed up for 1 year after initiation of either infliximab (n = 8) or etanercept (n = 2). Outcomes examined were within-subject differences in the tender entheseal count (TEC) and active joint count (AJC), markers of inflammation, functional assessments (Childhood Health Assessment Questionnaire [C-HAQ] score), and requirements for antirheumatic drugs.
Results:
At baseline, all patients exhibited active arthritis and enthesitis that were resistant to NSAIDs (n = 10), methotrexate (n = 6), sulfasalazine (n = 8), corticosteroids (oral n = 6, intravenous pulse n = 3, and intraarticular n = 6), and bisphosphonates (n = 2). In 2 patients, sulfasalazine (n = 2), corticosteroids (n = 1), and bisphosphonates (n = 1) were stopped after initiation of the anti-TNFalpha agent. In all patients, the arthritis and enthesitis significantly improved as evidenced by remission of the TEC and AJC by 6 months that was sustained during the 1-year followup, markers of inflammation and C-HAQ scores normalized, and there was a reduction in requirements for antirheumatic drugs (reduced dosage or discontinuation of NSAIDs n = 10, methotrexate n = 5, sulfasalazine n = 6, corticosteroids n = 4, and bisphosphonates n = 1).
Conclusion:
Anti-TNFalpha therapy is a potential novel treatment for refractory juvenile SpA. Further prospective studies are required to examine the effectiveness and long-term outcomes of anti-TNFalpha therapy in this cohort.
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