IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP

Abstract

Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Randomization strategy for eligible children. For this study, IVIG was Gamunex (immune globulin intravenous [human] 10%; this was marketed by Bayer at the start of the study, and then by Talecris and finally by Grifols). Gamunex was given according to manufacturer’s guidelines by means of a rapid infusion protocol: Start at 0.02 mL/kg per minute (1.2 mL/kg per hour) × 15 min. If no adverse reaction, increase to 0.04 mL/kg per minute (2.4 ml/kg per hour) × 15 minutes. If no adverse reaction, increase to 0.08 mL/kg per minute (4.8 mL/kg per hour) × 15 minutes. If no adverse reaction, increase to 0.10 mL/kg per minute (6.0 mL/kg per hour) for duration. If patients cannot sustain a particular infusion rate, then infusion is run at the highest tolerated rate.

Figure 2.

Analysis of covariance for PCs at 24 hours for the 2 regimens according to patient age. Best-fit lines for both regimens are plotted: placebo+IVIG (regimen A) and IVMP+IVIG (regimen B). Note that 24-hour PCs were obtained for 31 out of 32 patients (not obtained in a 1.2-year-old child).

Figure 3.

PCs (×109/L) in all children from baseline to 72 hours after intervention. Shown are the curves for children receiving regimen A (placebo+IVIG; red dashed line) and regimen B (IVMP+IVIG; blue solid line).

Figure 4.

Proportion of children with PC >20 × 109/L or >50 × 109/L for the 2 regimens over the first 72 hours.