Discussion
migraine, Headache, IVIG-related headache, headache
MIGRAINE, ADVERSE EVENT
Headache is clearly associated with IVIG therapy for PI, but not with PI itself. In this retrospective analysis, we analyzed pooled data from three clinical trials of a single IVIG agent to confirm and extend our understanding of headache and migraine associated with IVIG infusions. Our analysis provides a systematic evaluation of infusion times and rates of headache and migraine in a large population of patients receiving IVIG treatment for PI. Pooled analyses can be used to reaffirm data present in individual trials or to understand new concepts that may be better represented in a larger data set (Almost all patients achieved the maximum infusion rate specified in the product labeling, utilizing an infusion protocol with 15-minute rate escalation increments. Recent trials of other IVIG products have reported achieving per-protocol infusion rates in >90% of infusions, but with longer rate escalation increments (30 minutes vs 15 minutes for the IVIG formulations used in this analysis) (The observed rates of product-related headache (6.1% of infusions, 28.5% of patients) and migraine (0.5% of infusions, 4.1% of patients) occurred with 94.6% of patients achieving the maximum infusion rate, and use of a 15-minute rate escalation protocol. To place these results in context, headache rates reported in recent studies of IVIG in PI range from 2% to 22% on a per-infusion basis, and from 8% to 50.8% on a per-patient basis (Despite short (15-minute) escalation increments in the infusion protocol, rates of product-related headache were not significantly different for the 5% and 10% formulations in the entire population, the adult subgroup, and the pediatric subgroup, whether calculated at the infusion level or on a per-patient basis. In contrast to our results, 10% IVIG formulations have historically been associated with increased adverse event rates compared to 5% IVIG formulations (With IVIG therapy, first doses have been associated with more reported AEs than subsequent doses (Product-related headache and migraine were concentrated in a minority of patients, and only a small proportion of the total number of infusions were preceded with premedications. This finding should serve as a reminder that many patients may tolerate these infusions without difficulty and without the need for premedications. Perhaps greater emphasis on selecting patients most at risk for AEs would result in more judicious use of premedication.Rapid IVIG infusion is generally considered to be a risk factor for IVIG-related headache (This pooled analysis is limited by the open-label design of the studies that were pooled for the analysis, the retrospective nature of the analysis, and the relatively small number of patients included, although the data set includes a large number of infusions. The pediatric patients included in trials GMX04 and GMX07 may not have reported their headache and migraine complaints appropriately. Lack of randomization increases the risk of bias in the subgroup analyses. In addition, the data are drawn from clinical trials rather than routine practice. Because of these limitations, the results should be considered suggestive rather than conclusive. However, the information presented here may help clinicians mitigate headache and migraine AEs in patients receiving IVIG infusions for PI.In summary, this retrospective data analysis found in patients being treated with IVIG for PI, rates of headache (6.1%) and migraine (0.5%) were low for adult and pediatric patients and for both the 5% and 10% formulations. A large majority of infusions (94.6%) achieved the maximum infusion rate. Either formulation of this IVIG product can be administered using a 15-minute rate escalation protocol without excessive rates of headache or migraine.