Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease.
OBJECTIVE
To investigate the safety, tolerability, and pharmacokinetics of the anti-tumor necrosis factor-alpha monoclonal antibody infliximab in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).


METHODS
We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever after initial treatment with IVIG. Primary outcome measures were the safety, tolerability, and pharmacokinetics of infliximab. Secondary outcome measures were duration of fever and changes in markers of inflammation.


RESULTS
Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and in 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries.


CONCLUSIONS
Both infliximab and a second IVIG infusion were safe and well tolerated in the subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined.
Burns
Jane C
JC
Department of Pediatrics, University of California San Diego School of Medicine and Rady Children's Hospital San Diego, La Jolla, CA, USA.
Best
Brookie M
BM
Mejias
Asuncion
A
Mahony
Lynn
L
Fixler
David E
DE
Jafri
Hasan S
HS
Melish
Marian E
ME
Jackson
Mary Anne
MA
Asmar
Basim I
BI
Lang
David J
DJ
Connor
James D
JD
Capparelli
Edmund V
EV
Keen
Monica L
ML
Mamun
Khalid
K
Keenan
Gregory F
GF
Ramilo
Octavio
O
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D003323:Coronary Aneurysm / Q000000981:diagnostic imaging; D018592:Cross-Over Studies; D004351:Drug Resistance; D005260:Female; D005334:Fever / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007223:Infant; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D014463:Ultrasonography
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D000069285:Infliximab