Cost Utility of Lifelong Immunoglobulin Replacement Therapy vs Hematopoietic Stem Cell Transplant to Treat Agammaglobulinemia

Abstract

IMPORTANCELifelong immunoglobulin replacement therapy (IRT) is standard-of-care treatment for congenital agammaglobulinemia but accrues high annual costs ($30 000-$90 000 per year) and decrements to quality of life over patients' life spans. Hematopoietic stem cell transplant (HSCT) offers an alternative 1-time therapy, but has high morbidity and mortality.OBJECTIVE To evaluate the cost utility of IRT vs matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT to treat patients with agammaglobulinemia in the US. DESIGN, SETTING, AND PARTICIPANTSThis economic evaluation used Markov analysis to model the base-case scenario of a patient aged 12 months with congenital agammaglobulinemia receiving lifelong IRT vs MSD or MUD HSCT. Costs, probabilities, and quality-of-life measures were derived from the literature. Microsimulations estimated premature deaths for each strategy in a virtual cohort. One-way sensitivity and probabilistic sensitivity analyses evaluated uncertainty around parameter estimates performed from a societal perspective over a 100-year time horizon. The threshold for cost-effective care was set at $100 000 per quality-adjusted life-year (QALY). This study was conducted from 2020 across a 100-year time horizon.EXPOSURES Immunoglobulin replacement therapy vs MSD or MUD HSCT for treatment of congenital agammaglobulinemia MAIN OUTCOMES AND MEASURES The primary outcomes were incremental cost-effectiveness ratio (ICER) expressed in 2020 US dollars per QALY gained and premature deaths associated with each strategy. RESULTSIn this economic evaluation of patients with congenital agammaglobulinemia, lifelong IRT cost more than HSCT

Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future

“…Another approach to the treatment of primary B cell deficiencies includes allogenic HSCT as a curative therapy [ 84 ]. The overarching paradigm thus far has been that the defect in the humoral immune compartment can be addressed with immunoglobulin replacement therapy +/− antimicrobial prophylaxis [ 85 , 86 ].…”

Genetic obstacles to developing and tolerizing human B cells

“…For instance, mutation of TCF3 (Boisson et al, 2013)—which drives SLC expression—or haploinsufficiency of PU.1 (Le Coz et al, 2021)—which drives CD79B, IGHM, and BTK expression—also arrest B‐cell lymphopoiesis by affecting pre‐BCR assembling and signaling between the pro‐ and pre‐B cell stages. Regardless of genetic cause, B‐cell aplasia is associated with recurrent sino‐pulmonary infections preventable with lifelong immunoglobulin G replacement therapy (IRT) or, in certain circumstances, HSCT (Sun et al, 2021). Despite IRT B‐cell aplasia patients remain at higher risk of enteric infections, inflammatory bowel disease, gastrointestinal malignancies, and enteroviral meningoencephalitis potentially because IRT products do not replace luminal IgA (Barmettler et al, 2017; van der Meer et al, 1993; Winkelstein et al, 2006).…”

“…Although restoring B‐cell lymphopoiesis in an infant with SCID (Pai et al, 2014) or B‐cell aplasia (Le Coz et al, 2021; Sun et al, 2021) can be achieved directly with HSCT, restoring B‐cell tolerance in patients with genetically complex autoimmune diseases requires a more nuanced approach. Most autoantibody‐mediated diseases have been treated with B‐depleting therapies with mixed results (Kaegi et al, 2019).…”

High Drug Costs Hurt Health Outcomes—One Way or Another

“…A particularly well-done cost-utility analysis conducted by Sun and colleagues 4 appears in this issue of JAMA Pediatrics. This article presents a cost-effectiveness analysis comparing long-term immunoglobulin replacement therapy (IRT) with donor-matched related or unrelated stem cell transplantation (HSCT) for the treatment of congenital agammaglobulinemia.…”