Pediatric dosing of rituximab revisited: serum concentrations in opsoclonus-myoclonus syndrome.
To longitudinally assess serum concentrations of rituximab, it was administered intravenously to 25 children with opsoclonus-myoclonus syndrome at 375 mg/m2 on each of 4 consecutive weeks with (Group I and II) or without (Group III) conventional immunotherapy. Serum rituximab levels, drawn before and after each infusion and at later intervals, were analyzed by enzyme-linked immunosorbent assay. Rituximab concentration increased stepwise with each infusion, dropping by the next infusion, thereby forming 4 discrete peaks (Cmax) and troughs (Cmin). It then fell precipitously to trace levels at 4 months. However, Cmax and Cmin curves differed significantly between groups. Compared with the youngest children (Group I), the oldest (Group III) had a 34% lower rituximab concentration at the fourth infusion, 45% less IgM depletion 1 month later, and received 20% less rituximab when the dose was recalculated as mg/kg. Serum IgM and rituximab levels were negatively correlated. Peak rituximab concentration did not correlate with adrenocorticotropic hormone dose. These results indicate that the degree of serum IgM depletion is a useful indicator for rituximab dose equivalency in children of different ages. They also suggest that pediatric rituximab dosing should be based on body weight, not surface area. (ClinicalTrials.gov NCT00244361).
Pranzatelli
Michael R
MR
National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, IL, USA. mpranzatelli@siumed.edu
Tate
Elizabeth D
ED
Verhulst
Steven J
SJ
Bertolone
Salvatore J
SJ
Bhatla
Deepika
D
Granger
Meaghan
M
Lebowizc
Joseph
J
Lockhart
Sharon K
SK
Wiley
Joseph M
JM
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007167:Immunotherapy; D007223:Infant; D008297:Male; D053578:Opsoclonus-Myoclonus Syndrome / Q000276:immunology / Q000378:metabolism*; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D000069283:Rituximab; D000324:Adrenocorticotropic Hormone