Evaluation of IVIG for Prevention of Infections Occurring On-study and Treatment of Infection of Solid Organ Recipients With Secondary Antibody Deficiency: A Phase 2 Randomized Clinical Trial

Background. There is a paucity of data to guide the management of posttransplant secondary antibody deficiency (SAD). We aimed to evaluate the role of IVIG in solid organ recipients with SAD. Methods. A phase 2, randomized, multicenter, open-label study of solid organ recipients with severe infection and SAD defined as serum IgG <600 mg/dL. The study evaluated the efficacy of adding a fixed protocol of IVIG early after detection of SAD to standard of care (SOC) for the prevention of infection occurring on-study and the treatment of infections, versus SOC. We also assessed reconstitution of humoral immunity in a substudy. Forty‐four transplant recipients were randomized in 6 transplant centers in Spain. The IVIG protocol comprised 2 doses of 15 g (interval 7–15 d) followed by 3 doses of 20 g (interval 15–30 d). The primary endpoint was infection occurring on-study defined as a new severe infection after randomization. Results. Forty-two patients were included in the intention-to-treat analysis (IVIG arm, n = 21 versus non-IVIG arm, n = 21). The rate of infection occurring on-study was lower in patients randomized to receive IVIG versus SOC (23.8% versus 66.7%, Fisher exact test, P = 0.012). The median number of infections occurring on-study was lower in the IVIG group. The median total number of new admissions considered to be related to an infection occurring on-study was significantly lower in IVIG-treated patients. A significant increase in specific anti-cytomegalovirus IgG, anti–varicella zoster IgG, anti- Clostridium difficile toxins A and B IgG, and anti-tetanus toxoid IgG and IgG1 was demonstrated in the IVIG arm. Conclusions. In solid organ recipients with severe infection and SAD, IVIG may reduce infection occurring on-study occurrence versus SOC.