A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma

To determine the efficacy of high doses of intravenous gammaglobulin (IVIG) for the treatment of severe, steroid-dependent asthma in patients between 6 and 68 years of age, a randomized, double-blind, placebo-controlled multi center clinical trial was conducted in private and university hospitals in the United States. Patients were randomized to one of three treatment arms: 2 g IVIG/kg/month (16 patients); 1 g IVIG/kg/month (9 patients); or 2 g iv albumin (placebo)/kg/month (15 patients). The treatment consisted of seven monthly infusions followed by a posttreatment observation period. The prim ary outcome measurement was mean daily prednisone-equivalent dose requireme nts, determined during the observation month preceding initiation of treatm ent and compared to the month preceeding the seventh infusion. Secondary cl inical endpoints measured were pulmonary function, frequency of emergency r oom visits or hospitalizations, and number of days absent from school or wo rk. When adjusted for body weight, the mean dose requirements fel by 33, 39 , and 33% in the placebo, IVIG (1 g/kg), and IVIG, (2 g/kg) treatment arms, respectively. The differences between therapies wee not statistically diff erent (P = 0.9728). The mean percentage-of-predicted FEV1 fell in all three treatment groups during the treatment period but there was no significant difference between treatment groups (P = 0.8291). There was also no signifi cant difference in the percentage of subjects requiring emergency room visi ts or hospitalizations or missing days or work/school, among the three trea tment groups. The trial was terminated prematurely after interim analysis d etermined the adverse experience rate was different between the three group s. Three patients, all randomized to the 2-g/kg IVIG dose group, were hospi talized wit symptoms consistent wit aseptic meningitis. In summary, in this randomized, double-blind, placebo-controlled multicenter study, high doses of IVIG did not demonstrate a clinically or statistically significant adva ntage over placebo (albumin) infusions for the treatment of corticosteroid- dependent asthma. Subgroup analysis failed to identify markers predicting r esponsiveness. High-dose IVIG can also bo associated with a significant inc idence of serious adverse events. (C) 1999 Academic Press.