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It is important to keep patients with long-term primary immunodeficiencies that benefit from immunoglobulin therapy on the costly but life-saving preparation prescribed
David Watters
Executive Director
International Patient Organisation for Primary Immunodeficiencies
Downderry
UK
There are three types of immune disorders: primary (genetic) defects of the immune system; secondary (acquired) defects of the immune system (eg, HIV, CMV, etc); and auto‑immune disorders such as lupus ertematous disease, arthritis, etc. Not all primary immunodeficiencies (PIDs) can be treated with immunoglobulin; examples of these are phagocyte deficiencies, neutropenias and complement deficiencies. Of all PIDs, 60% relate to B- and T-cell problems.
Primary immunodeficiencies are at the cutting edge of medical science all over the world. It is estimated that of the global population who have PIDs, only about 5% have been diagnosed. It is thought that even in advanced nations such as the UK, around 50% remain undiagnosed. The reason for this is that PID symptoms are similar – although not identical – to those of an array of other disorders. Furthermore, in many cases PID may not develop until patients reach adulthood or even early middle age. Nevertheless, a key point is that while the symptoms resemble those of other disorders, they are unique in that they are merely a manifestation of an underlying condition: all too often the symptoms are treated without looking at the underlying cause. At pharmacy level, it would be interesting to survey patients who have often repeated prescriptions for antibiotics that show no beneficial effect. Such patients might in fact have a PID, and might benefit much more from immunoglobulin therapy which would boost their immune response and radically improve their overall health and quality of life. PIDs are lifelong disorders and as such need long-term planning within the healthcare structure of any country.
The special nature of immunoglobulins
Unlike most prescription medicines, immunoglobulin is derived from human plasma. Plasma-derived products also include clotting factors. Plasma derivatives are unique in relying on human body fluid – plasma – as their source material. This has many implications. In the past we have seen infection with HIV and hepatitis, in various forms, due to inadequate product safety. While those days are hopefully behind us – at least as far as HIV and hepatitis are concerned – manufacturers and clinicians are constantly on the alert for any new threat that might develop. So there is an element of risk involved with administering plasma-derived products, which will have been carefully explained to patients by clinicians before therapy started. This also means immunoglobulins are costly. Nowadays, for example, in the UK we do not use locally collected plasma for making plasma derivatives because of perceived risks arising from variant Creutzfeld-Jakob disease (vCJD). All UK-used plasma is imported, with most of it “harvested” in the USA. It costs more than $100 just to collect a basic unit of plasma; there are still long and careful quarantine processes to go through before the actual manufacturing stage is reached. The quarantine period is important because, especially for first-time donors, a donation is not used until after a second donation has been made – that is to say, until there has been an opportunity to look ahead at the safety of the donor plasma. The regulatory authorities are naturally as anxious as the patients and clinical staff to ensure that the end-product is as free as possible from known contaminants. This means the manufacturing process itself is costly.
The industry has been sensitive about overproducing costly plasmatics for which the market may be limited. This is done by closing down plasma collection centres. Centres are very easy to close, but much more difficult to re-open, with a timeline of years rather than months between opening a facility and collected plasma reaching the veins of those who rely so much on the product. This is why product shortages occur from time to time. Manufacturing plasma derivatives is infinitely more complex than producing painkillers or antibiotics, demanding a greater measure of understanding than is the case with most other pharmaceuticals.
Another special feature of immunoglobulins is that they are emphatically not “all the same” – they are certainly not interchangeable and patients do not tolerate all “brands” equally. Consider this: part of the process of being placed on immunoglobulin therapy involves the clinician and nursing staf fensuring the patient both tolerates and benefits from a particular product. The task for the clinician and nursing staff is to identify which specific immunoglobulin preparation does not cause an allergic reaction – especially a major one. This will be worked out carefully and painstakingly so that the patient can derive the maximum benefit from this costly medication.
Immunoglobulin: a multi-use plasmatic
Pharmacists will be aware that immunoglobulin is used by more than one group of patients. The industry is happy that there is a growing list of conditions that appear to benefit from immunoglobulin therapy. However, patient organisations and regulatory authorities – such as the EMEA – are nervous about the growing list of conditions that appear to benefit from therapy “off-label”, and call for agreed priority for use by groups with lifelong need for immunoglobulin who clearly do benefit from the therapy before making the precious and costly preparation available to those for whom it is an experimental option. Too often we hear of those with short-term, high-volume requirements clearing the pharmacy supply of immunoglobulin overnight and leaving people with long-term needs without their vital and life-saving therapy.
Conclusion
Within the hospital pharmacy setting, it is wise to:
- Agree which patient categories clearly benefit from immunoglobulin therapy.
- Negotiate with clinical immunology staff on their need for the different “brands” of immunoglobulin.
- Securely ring-fence those supplies against use by other specialists whose patients do not fall within the agreed list of those who benefit.
Guidance on the above is available from the EMEA.(1)
Reference
1. European Agency for the Evaluation of Medicinal Products. Core SPC for human normal immunoglobulin for subcutaneous and intramuscular use. EMEA/CPMP/BPWG/282/00. London: EMEA; 2002. Available at: www.emea.europa.eu/pdfs/human/bpwg/028200en.pdf
