Efficacy and consumption of human immunoglobulin: rapid health technology assessment - scoping review
Health technology assessment
|Published
The National System for Managed Introduction of New Health Technologies in Norway asked us to summarize research evidence on the efficacy of human immunoglobulin. Furthermore, we were asked to identify therapeutic areas where the consumption of these drugs in Norway is increasing and where there is variation between health trusts.
Key message
Human immunoglobulin is derived from blood plasma and can be used to treat a variety of diseases. For some conditions, treatment efficacy is documented. For other diseases, a beneficial clinical effect is uncertain. The availability of human immunoglobulin depends on blood donations and is therefore limited.
The National System for Managed Introduction of New Health Technologies in Norway asked us to summarize research evidence on the efficacy of human immunoglobulin. Furthermore, we were asked to identify therapeutic areas where the consumption of these drugs in Norway is increasing and where there is variation between health trusts. We collaborated with The Norwegian Hospital Procurement Trust and a group of experts from different clinical fields.
- We included 63 systematic reviews and 4 primary studies that investigated the efficacy of immunoglobulin in patients who receive this treatment in Norwegian medical practice.
- For many conditions that are being treated with immunoglobulin, research on its efficacy is limited.
- The amount of human immunoglobulin used has increased by 55 % and incurred expenses by 119 % from 2016 to 2020.
- In some Norwegian counties, almost three times as much immunoglobulin had been used compared to counties with the lowest consumption in 2020.
- Immunoglobulins were mostly used for hematological, neurological and immunological diseases, making up 87 % of all treatments in 2020.
A possible prioritization of patient populations in Norway can build on existing guidelines and recommendations in other countries.
Summary
Introduction
Human immunoglobulin is produced from plasma derived from blood donors. These drugs consist of antibodies that can protect against infections and are used to treat a wide variety of diseases, among others hereditary (primary) immunodeficiencies and deficiencies following other treatment or diseases (secondary), as well as autoimmune and inflammatory diseases. For some conditions, the treatment is lifesaving, while for other diseases alternative treatment options exist.
In Norway, human immunoglobulin is used in the medical fields of immunology, hematology, neurology, rheumatology, skin diseases, pediatric and infectious disease, as well as treatment of malignancies and transplantation. The drugs are administered intravenously or subcutaneously. Some patients may receive repeated and lifelong treatment, for example in the case of primary immunodeficiency. For other conditions, for example the neurological disease Guillain-Barré syndrome, immunoglobulin is an acute treatment. In situations with limited supply, there may be a need to prioritize patients or patient groups.
The availability of human immunoglobulin is limited and may be uncertain as its production depends on blood donations. Norway is not self-sufficient with human immunoglobulin, but depends to a large extent on donations in other countries, first and foremost in the USA. The costs are high and the use of these medicines is increasing in Norway and globally.
Objective
We aimed to conduct a scoping review of the clinical research literature on the efficacy of human immunoglobulin in a selection of diseases and conditions where these drugs are currently used in Norway. With this rapid health technology assessment, we mapped the consumption of and costs incurred by human immunoglobulin use in Norway. We further aimed to unveil possible variations in use by geographical regions and between clinical disciplines.
Method
We limited the scope of this health technology assessment to map the evidence base of efficacy in patients who receive human immunoglobulin in Norwegian medical practice. We developed a list of relevant diseases in co-operation with external experts. For the selected conditions, we searched for review literature (systematic reviews and health technology assessments) published during the past five years and for primary studies where we could not find reviews.
We extracted data from the included reviews and present them in tables as the results were reported in the original reviews. We have not conducted our own analyses. We have not explicitly assessed the quality of the included reviews and studies. We have not made confidence judgements in the results.
The Norwegian Institute of Public Health co-operated with The Norwegian Hospital Procurement Trust and calculated the consumption of human immunoglobulin in Norway. Here, we used data from Farmastat and Sykehusapotekenes legemiddelstatistikk, respectively. We analysed both consumption and costs on a national level from 2016 to 2020. To investigate possible geographical differences, we mapped consumption at county level. Here, we present both absolute figures and consumption relative to population size. We also gathered data from the innsatsstyrt finansiering («effort driven financing») database and calculated consumption in different medical fields.
Results
We included 63 systematic reviews and 4 primary studies that summarize the efficacy of immunoglobulin in conditions treated in Norway. For some diseases, efficacy has been explored in randomised controlled trials. For many conditions, research evidence is limited to cohort studies, case series and case reports.
The consumption of human immunoglobulin has increased by 55 % between 2016 and 2020. Both intravenous and subcutaneous use is on the rise. From 2019 to 2020, this increase was lower than during the previous years. Data for 2021 point to a reduction in annual usage compared to 2020.
Total consumption is up to three times higher in counties that use the largest volume of immunoglobulin (Nordland, Troms and Finnmark) compared with counties where their use is lowest (Trøndelag, Vestland) adjusted for population size.
Human immunoglobulin is most used in the fields of hematology, neurology and immunology, which together made up for 87 % of all patients treated in 2020. Patients who received intravenous immunoglobulin that year most frequently suffered from a hematological or neurological disease, primary or secondary immunodeficiency. Subcutaneous immunoglobulin, which can be self-administered in outpatient treatment, is mostly used for immunological conditions.
Discussion
For many conditions where immunoglobulin is used as treatment, research evidence of its efficacy is insufficient. Many conditions are rare and to conduct robust effect studies can therefore be difficult.
Both consumption of human immunoglobulin and costs associated with these medicines have increased substantially in Norway between 2016 and 2020. The increase from 2019 to 2020 was lower compared to previous years. Preliminary numbers for 2021 indicate a lower annual consumption than during the year of 2020 and may have been impacted by the COVID-19 pandemic. Less availability of blood donations globally may have contributed to the increase in costs.
We expect the consumption of human immunoglobulin to increase further in years to come, for example among patients with immunodeficiencies following cancer treatment. In a possible future shortage of these drugs, there may not be enough human immunoglobulin available for all patients.
This development is in line with the overall increasing usage in Scandinavia, in other European countries and globally. Our analyses show variable prescribing patterns for these drugs within Norway. We believe that regional differences in medical practice in part are due to the lack of national guidelines.
If further efforts are to be taken in this domain, we believe it is necessary to include recommendations for use in addition to an assessment of research evidence. Existing international guidelines for their use rely heavily on clinical experience, among other factors. International guidelines can be adapted to the Norwegian context. If priority settings are to be developed, they should cover all relevant medical disciplines.
Conclusion
We found evidence of efficacy for diagnoses that are indicated for treatment with human immunoglobulin. We identified research on their efficacy also for diseases that at present are treated off-label, that is for unapproved indications. For such conditions, the evidence of efficacy is usually very limited.
The consumption of human immunoglobulin in Norway has increased by 55 % between 2016 and 2020. Their costs have increased by 119 % during the same period. Immunoglobulin is mostly used within the medical disciplines of hematology, neurology and immunology. These medicines are not uniformly used throughout Norway. In the northernmost counties, total immunoglobulin consumption was almost three times as high as in counties with least usage during the past year.
