Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondylarthropathy.
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).


CONCLUSIONS
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.
Division of Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. shirley.tse@sickkids.ca
Shirley M L
SM
Tse
Ruben
R
Burgos-Vargas
Ronald M
RM
Laxer
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D000068800:Etanercept; D005260:Female; D006304:Health Status; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D010865:Pilot Projects; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012074:Remission Induction; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept