Dosing Strategy of Immunoglobulin (IgG) Replacement Therapies in Obese and Overweight Patients with Primary Immunodeficiency Diseases (PIDDs): A Meta-Analysis of Clinical Trials.

Abstract

The current dosing strategy of immune globulin products for the treatment of primary immunodeficiency diseases (PIDDs) in the USA is based on total body weight (BW). The aim of our study was to assess the relationship between dose and trough level, and to determine whether an alternative dosing strategy should be considered for patients who are overweight or obese. We analyzed data in a total of 533 patients from 11 studies. We modeled the relationship between trough level and dose per week using a linear mixed model. We used an over-dispersed Poisson model to model the relationship between infection and trough level. In these analyses, we then combined the study-specific treatment effects using a random-effect or fixed-effect model. The mean administered dose per week was 9.77, 14.00, or 18.17g in patients who were normal weight, overweight, or obese, respectively. Compared with a patient of normal weight, a 1g increase in dose per week in a patient who was overweight was associated with a smaller increase in the trough level, 0.08g/L less (95%CI -0.14 to -0.03g/L), and a 1g increase in dose per week in a patient who was obese was associated with a much smaller increase in trough level, 0.01g/L less (95%CI -0.07 to 0.06g/L). Last, for a 1unit (g/L) increase in trough level, the expected number of infections remained the same, with a multiplicative factor of 1.01 (95%CI 0.98-1.04). Overall, we found no compelling evidence to justify a reconsideration of the current dosing strategy based on total BW for patients with PIDDs who are overweight or obese.