Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study.
OBJECTIVE
To evaluate the efficacy and safety of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (infliximab) with methotrexate (MTX) in juvenile idiopathic arthritis (JIA) with an active polyarticular course that is not responsive to MTX.


METHODS
Twenty-four young adults with long-lasting, refractory JIA were enrolled in an open, prospective, 2-year pilot study. Patients received intravenous infliximab at 3 mg/kg of body weight at weeks 0, 2, and 6 and every 8 weeks thereafter, with weekly subcutaneous MTX.


RESULTS
The median duration of therapy was 9.1 months. Significant improvements were observed in the number of joints (28-joint count) with active disease (median 6 at baseline, 2 at 2 weeks, 0 at 6 months, 0 at 1 year; P < 0.05). Pain as well as patient's and physician's global assessments of disease status were assessed on 0-100-mm (0 = best; 100 = worst) visual analog scales (VAS). There were significant improvements in VAS pain scores (45 at baseline, 25 at 2 weeks, 8.5 at 6 months, 10 at 1 year; P < 0.05), patient's global assessment of disease status (50 at baseline, 22 at 2 weeks, 11.5 at 6 months, 18 at 1 year; P < 0.05), and physician's global assessment of disease status (50.5 at baseline, 22.5 at 2 weeks, 6.5 at 6 months, 10 at 1 year; P < 0.01). In addition, there were significant improvements in the erythrocyte sedimentation rate (64 mm/hour at baseline, 36 mm/hour at 2 weeks, 23.5 mm/hour at 6 months, 35 mm/hour at 1 year; P < 0.01) and C-reactive protein level (4.9 mg/dl at baseline, 2.8 mg/dl at 2 weeks, 3.1 mg/dl at 6 months, 3.2 mg/dl at 1 year; P < 0.005). The percentage of patients meeting the American College of Rheumatology 20% improvement criteria at each assessment ranged from 54.2% to 86.7%. Of the responses on the Disease Activity Score in 28 joints, 37.5-63.6% were classified as "good," 14.3-33.3% were classified as "moderate," and 18-37.5% were classified as "no response." Twelve patients (50%) had adverse events, and 5 patients (20.8%) withdrew.


CONCLUSIONS
Infliximab plus MTX showed high effectiveness and safety in short- and medium-term treatment of long-lasting refractory JIA. A controlled multicenter clinical trial is needed.
Gerloni
Valeria
V
Istituto G. Pini, Milan, Italy. gerloni@gpini.it <gerloni@gpini.it>
Pontikaki
Irene
I
Gattinara
Maurizio
M
Desiati
Francesca
F
Lupi
Elide
E
Lurati
Alfredomaria
A
Salmaso
Alessandra
A
Fantini
Flavio
F
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D000069285:Infliximab; D007262:Infusions, Intravenous; D008727:Methotrexate / Q000008:administration & dosage; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D002097:C-Reactive Protein; D000069285:Infliximab; D008727:Methotrexate