Adult antibody deficiency in Hong Kong : burden, clinical characteristics and feasibility of subcutaneous immunoglobulin replacement

Abstract

Adult antibody deficiency, particularly secondary antibody deficiency, is a prevalent yet frequently under-reported and under-diagnosed condition both globally and in this locality. Its prevalence has been rising, especially with the increasing application of cytotoxic agents such as anti-CD20 monoclonal antibodies in treating various haematological and autoimmune disorders. However, studies on the epidemiology, disease burden and clinical characteristics of adult antibody deficiency were lacking, especially in Asia and among Chinese. With the scarcity of clinical data on secondary antibody deficiencies, treatment of secondary antibody deficiency had been largely referenced from that of primary antibody deficiency. However, the contrast of clinical characteristics between primary and secondary antibody deficiency patients were unclear. Also, the quality of life of primary and secondary antibody deficiency patients had never been directly compared. Subcutaneous immunoglobulin replacement has emerged in recent years as an alternative treatment modality to the traditional intravenous immunoglobulin replacement for antibody deficiency. Clinical studies in Western countries, mostly on primary antibody deficiency patients and few on secondary antibody deficiency patients, found that subcutaneous immunoglobulin replacement was associated with higher trough serum IgG levels, similar or fewer infections, fewer systemic adverse effects, better quality of life, and lower healthcare cost. However, its effectiveness in Asia and among Chinese was largely unknown. In view of the aforementioned knowledge gaps, this series of studies was conducted to investigate the burden and clinical characteristics of adult antibody deficiency, and the feasibility of subcutaneous immunoglobulin replacement in Hong Kong. In Study 1, Population-wide data of normal immunoglobulin consumption over the past 10 years were collected to evaluate the longitudinal trends of the burden of antibody deficiency in Hong Kong. Distribution of indications of normal immunoglobulin, hence the causes of antibody deficiency, as well as the distribution of diagnoses among adult immunodeficiency patients under immunologist’s care in Queen Mary Hospital (Hong Kong) were also studied. In Study 2, a cohort of adult antibody deficiency patients were recruited in Queen Mary Hospital (Hong Kong). Direct comparisons on the clinical characteristics and quality of life were made between primary and secondary antibody deficiency patients, as well as between those on conservative treatment and those on immunoglobulin replacement. Among the subgroup of patients on immunoglobulin replacement, the clinical features, serum immunoglobulin levels, clinical outcomes, adverse effects and quality of life of patients on intravenous immunoglobulin replacement and subcutaneous immunoglobulin replacement were compared. The healthcare costs using these 2 modalities of treatment were estimated and compared. In Study 1, there was a significant increasing trend in both normal immunoglobulin consumption and the number of immunoglobulin recipients in Hong Kong, indicating a rising burden of antibody deficiency over the past decade. The majority of adult normal immunoglobulin recipients had secondary antibody deficiency, with haematological diseases being the most common aetiologies. Antibody deficiency accounted for about 40% of adult immunodeficiency patients managed by clinical immunologists. However, most of the secondary antibody deficiency patients did not receive immunology specialist’s care. With the growing burden of adult antibody deficiency, normal immunoglobulin consumption, and under-representation of secondary antibody deficiency, strategies to optimise immunoglobulin use are warranted to maintain sustainability; more healthcare resources, including immunology specialist service, shall be directed towards secondary antibody deficiency, with shared care between immunologists and non-immunologists being a potential solution. In Study 2, patients with secondary antibody deficiency were generally older, experienced a later onset and diagnosis age, but had a shorter diagnostic delay, alongside exhibiting higher IgA levels and CD4:CD8 ratios compared to those with primary antibody deficiency. Notably, clinical outcomes relating to infections and hospitalisations due to immunodeficiency were comparable between both groups. While both groups reported poorer health-related quality of life in contrast to the general population, patients with secondary antibody deficiency experienced significantly worse physical health-related quality of life when directly compared to those with primary antibody deficiency. Patients on immunoglobulin replacement therapy had lower baseline IgG and IgA levels and B-cell counts compared to those receiving conservative treatment. Although the latest (trough) IgG levels were similar across both groups, the trough IgA levels remained lower among those on immunoglobulin replacement. In terms of clinical outcomes, patients receiving immunoglobulin replacement experienced more hospitalisations related to immunodeficiency; but still, their health-related quality of life was comparable to those receiving conservative management. These findings indicate that secondary antibody deficiency imposes a greater disease burden on patients, while immunoglobulin replacement appears to be an effective treatment for adults with antibody deficiencies that does not adversely affect health-related quality of life. The subgroup analysis of patients receiving immunoglobulin replacement therapy revealed that those treated with subcutaneous immunoglobulin exhibited more favourable clinical outcomes and improved health-related quality of life compared to their those on intravenous immunoglobulin. In this real-world study, despite lower doses of immunoglobulin were used in among those on subcutaneous immunoglobulin, both groups achieved comparable trough serum IgG levels and infection rates, suggesting that subcutaneous immunoglobulin could be a more drug-saving treatment modality. Therefore, switching from intravenous to subcutaneous immunoglobulin replacement may be a viable strategy for optimising immunoglobulin consumption. Financially, subcutaneous immunoglobulin replacement was more cost-effective than intravenous immunoglobulin when accounting for both drug costs and associated treatment expenditures. In light of these encouraging findings and their clinical and health-economic implications, broader adoption and subsidisation of subcutaneous immunoglobulin replacement in Hong Kong is advocated.