Immunoglobulin replacement vs prophylactic antibiotics for hypogammaglobulinemia secondary to hematological malignancy.

ABSTRACT: Immunoglobulin replacement and prophylactic antibiotics are commonly used to prevent infections in patients with secondary hypogammaglobulinemia due to hematological malignancies but have never been directly compared. In this randomized controlled feasibility trial conducted in 7 hospitals in Australia and New Zealand, we enrolled patients with secondary hypogammaglobulinemia with either a history of recurrent/severe infection or an immunoglobulin G level <4 g/L. Participants were randomized in a 1:2 ratio to immunoglobulin (0.4 g/kg per 4 weeks IV) or daily antibiotics (trimethoprim-sulfamethoxazole 160 mg/800 mg or, if contraindicated, 100 mg doxycycline) for 12 months. Participants allocated to antibiotics were allowed to crossover after grade ≥3 infections. The primary outcome was proportion of patients alive on the assigned treatment 12 months after randomization. Between August 2017 and April 2019, 63 patients were randomized: 42 to antibiotics and 21 to immunoglobulin. Proportion of participants alive on allocated treatment at 12 months was 76% in the immunoglobulin and 71% in the antibiotic arm (Fisher exact test P=.77; odds ratio, 0.78; 95% CI, 0.22-2.52). The lower quartile for time to first major infection (median, not reached) was 11.1 months for the immunoglobulin and 9.7 months for the antibiotic arm (log-rank test, P=.65). Three participants in the immunoglobulin and 2 in the antibiotic arm had grade ≥3 treatment-related adverse events. A similar proportion of participants remained on antibiotic prophylaxis at 12 months to those on immunoglobulin, with similar rates of major infections. Our findings support the feasibility of progressing to a phase 3 trial. Trial registration #ACTRN12616001723471.

Economic evaluation: immunoglobulin vs prophylactic antibiotics in hypogammaglobulinemia and hematological malignancies.

ABSTRACT: Patients with hematological malignancies are at high risk of developing hypogammaglobulinemia (HGG) and infections. Immunoglobulin (Ig) is one recommended option to prevent these infections, but it is expensive, and its cost-effectiveness compared with other prevention strategies remains unknown. We conducted a trial-based economic evaluation from the Australian health care system perspective to estimate the 12-month cost-effectiveness of prophylactic Ig vs prophylactic antibiotics in 63 adults with HGG and hematological malignancies participating in the RATIONAL feasibility trial. Two analyses were conducted: (1) cost-utility analysis to assess the incremental cost per quality-adjusted life year (QALY) gained; and (2) cost-effectiveness analysis to assess the incremental cost per serious infection prevented (grade ≥3) and per any infection (any grade) prevented. Over 12 months, the total cost per patient was significantly higher in the Ig group than in the antibiotic group (mean difference, AU$29 140; P < .001). Most patients received IVIg, which was the main cost driver; only 2 patients in the intervention arm received subcutaneous Ig. There were nonsignificant differences in health outcomes. Results showed Ig was more costly than antibiotics and associated with fewer QALYs. The incremental cost-effectiveness ratio of Ig vs antibiotics was AU$111 262 per serious infection prevented, but Ig was more costly and associated with more infections when all infections were included. On average and for this patient population, Ig prophylaxis may not be cost-effective compared with prophylactic antibiotics. Further research is needed to confirm these findings in a larger population and considering longer-term outcomes. The trial was registered at the Australian and New Zealand Clinical Trials Registry as #ACTRN12616001723471.